Insulinoma: A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Adenoma, Islet Cell: A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Cell Line, Tumor: A cell line derived from cultured tumor cells.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.DNA Fragmentation: Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Insulin-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Nesidioblastosis: An inherited autosomal recessive syndrome characterized by the disorganized formation of new islets in the PANCREAS and CONGENITAL HYPERINSULINISM. It is due to focal hyperplasia of pancreatic ISLET CELLS budding off from the ductal structures and forming new islets of Langerhans. Mutations in the islet cells involve the potassium channel gene KCNJ11 or the ATP-binding cassette transporter gene ABCC8, both on CHROMOSOME 11.X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Hypoglycemia: A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Mice, Inbred C57BLMembrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Proinsulin: A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Caspase 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Pancreatectomy: Surgical removal of the pancreas. (Dorland, 28th ed)Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Group VI Phospholipases A2: A calcium-independent phospholipase A2 group that may play a role in membrane phospholipid remodeling and homeostasis by controling the levels of PHOSPHATIDYLCHOLINE in mammalian cell membranes.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Glucose Transporter Type 2: A glucose transport facilitator that is expressed primarily in PANCREATIC BETA CELLS; LIVER; and KIDNEYS. It may function as a GLUCOSE sensor to regulate INSULIN release and glucose HOMEOSTASIS.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Myeloid Cell Leukemia Sequence 1 Protein: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.Receptors, Glucagon: Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Glucagonoma: An almost always malignant GLUCAGON-secreting tumor derived from the PANCREATIC ALPHA CELLS. It is characterized by a distinctive migratory ERYTHEMA; WEIGHT LOSS; STOMATITIS; GLOSSITIS; DIABETES MELLITUS; hypoaminoacidemia; and normochromic normocytic ANEMIA.Calcium Gluconate: The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Octreotide: A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Caspase 2: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Xenograft Model Antitumor Assays: In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Pancreas: A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Mice, Inbred BALB CHeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Fas-Associated Death Domain Protein: A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Receptor-Like Protein Tyrosine Phosphatases, Class 8: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.Proprotein Convertase 2: A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Recombinant Proteins: Proteins prepared by recombinant DNA technology.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Secretagogins: Secretagogins are EF HAND MOTIF-containing calcium-binding proteins that are involved in early neuronal migration and neurogenesis. They are also present in many adult organs and in brain and endocrine neoplasms.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Blood Glucose: Glucose in blood.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Glucagon-Like Peptide 1: A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Multiple Endocrine Neoplasia Type 1: A form of multiple endocrine neoplasia that is characterized by the combined occurrence of tumors in the PARATHYROID GLANDS, the PITUITARY GLAND, and the PANCREATIC ISLETS. The resulting clinical signs include HYPERPARATHYROIDISM; HYPERCALCEMIA; HYPERPROLACTINEMIA; CUSHING DISEASE; GASTRINOMA; and ZOLLINGER-ELLISON SYNDROME. This disease is due to loss-of-function of the MEN1 gene, a tumor suppressor gene (GENES, TUMOR SUPPRESSOR) on CHROMOSOME 11 (Locus: 11q13).Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The amyloid formation might be a major mediator of apoptosis, or programmed cell death, in the islet β-cells. Initially, the ... 1987). "Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like ... The overall effect is an apoptosis cascade initiated by the influx of ions into the β-cells. In summary, impaired N-terminal ... Proislet amyloid polypeptide (proIAPP, proamylin, proislet protein) is produced in the pancreatic beta cells (β-cells) as a 67 ...
The cells in tubular adenomas, like most tumors which frequently progress to cancer, show certain abnormalities of cell ... migration and apoptosis (programmed cell death), causing the growth of benign tumors. Tuberous sclerosis complex (TSC) is an ... Insulinomas can produce large amounts of insulin leading to hypoglycemia. Pituitary adenomas can cause elevated levels of ... Benign neoplasms are typically but not always composed of cells which bear a strong resemblance to a normal cell type in their ...
Insulinoma[edit]. Insulinoma is a rare tumor derived from the neoplasia of beta cells. Insulinomas are usually benign, but may ... "Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died ... Beta cellscells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells ... Then the cytokines activate CD8+ cytotoxic-T cells, which lead to beta-cell destruction.[18] The destruction of these cells ...
January 2007). "Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38- ... Opening these channels leads to hyperpolarization of cell membrane, a decrease in calcium influx, and a subsequently reduced ... thus it is used to counter hypoglycemia in disease states such as insulinoma (a tumor producing insulin) or congenital ... Diazoxide is one of the most potent openers of the K+ ATP channels present on the insulin producing beta cells of the pancreas ...
VMATs are found in a variety of cell types throughout the body, however, VMAT1 is found exclusively in neuroendocrine cells, in ... they found VMAT1 and VMAT2 were located in mutually exclusive cell types, and that in insulinomas VMAT2 activity disappeared, ... which can induce apoptosis, due to the presence of H2S. VMAT1 (SLC18A1) maps to a shared bipolar disorder(BPD)/schizophrenia ... Specifically, VMAT1 is found in chromaffin cells, enterochromaffin cells, and small intensely fluorescent cells (SIFs). ...
... causing growth arrest and/or apoptosis of hormone-responsive cancer cells. Letrozole and anastrozole are aromatase inhibitors ... The target recepetor may be on the cell surface, as in the case of peptide and glycoprotein hormones, or it may be ... including the Zollinger-Ellison syndrome of gastrinoma and the chronic hypoglycemia of insulinoma. It is also effective in ... The exact mechanism of action of these hormones is unclear, and may involve both direct effect on the tumor cells (suppression ...
... in PC3 cells, BLT2 receptors stimulate the NF-κB pathway to inhibit the apoptosis caused by cell detachment from surfaces (i.e ... Cultured RINm5F rat Insulinoma cells convert 12(S)-HpETE to hepoxilin A3 in a reaction that is comletely dependent on, and co- ... T lymphocye cell line), Hut78 cells (T cell lymphoma cell line), HEK 293 cells (primary embryonic kidney cell line), MCF7 cells ... Further studies in animal models suggest that the 12S-HETE made by pancreatic beta cells (or possibly alpha cells or other cell ...
Another hypothesis says that c-MET may control β-cell apoptosis because a lack of c-MET causes increases cell death but the ... These changes in the β-cells cause increased insulin secretion as a result of increased β-cell proliferation.[22] HGF/c-MET has ... islet cell antibodies and/or insulinoma antigen-2), women with more than two previous pregnancies, and women who were obese (in ... β-cell adaption refers to the change that pancreatic islet cells undergo during pregnancy in response to maternal hormones in ...
The cells in tubular adenomas, like most tumors which frequently progress to cancer, show certain abnormalities of cell ... migration and apoptosis (programmed cell death), causing the growth of benign tumors.[21] ... Insulinomas can produce large amounts of insulin leading to hypoglycemia.[8][9] Pituitary adenomas can cause elevated levels of ... Benign neoplasms are typically but not always composed of cells which bear a strong resemblance to a normal cell type in their ...
1B). That apoptosis contributes at least partly to palmitate-induced cell death in MIN6 insulinoma cells was evidenced by ... Cell culture of mouse insulinoma cells.. MIN6 cells were maintained in Dulbeccos modified Eagles medium (DMEM) containing 25 ... Fatty acids induce dose-dependent apoptosis in MIN6 cells.. Glucose-responsive MIN6 insulinoma cells were assessed for ... Oleate administration of insulinoma cells induced apoptosis that was dependent on decreased protein kinase B/Akt ...
Cell viability, apoptosis, glucose-stimulated insulin secretion, Bcl-2, and Bax gene expression levels, mitochondrial membrane ... Long-term exposure of INS-1 rat insulinoma cells to linoleic acid and glucose in vitro affects cell viability and function ... on rat insulinoma INS-1 β cells was investigated. INS-1 cells were incubated with 0, 50, 250 or 500 μM linoleic acid/0.5% (w/v ... The results of this study indicate that chronic exposure to linoleic acid-induced β-cell dysfunction and apoptosis, which ...
The effect of cell cycle phase on the seven key pro-cell cycle molecules in INS1 cells. A: FACS histogram of INS1 cells grown ... The effect of combined overexpression of the seven cell cycle activators on rat β-cell death. β-Cell apoptosis was measured by ... The effect of glucose on key cell cycle proteins in rat islets and INS1 cells. A: Cell cycle distribution of rat islet cells ... The G1/S proteome of the four rodent insulinoma cell lines. MIN6 and BTC3 cell lines are compared with mouse islets (M isl). ...
These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell ... Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells ( ... T Cells Cooperate With Palmitic Acid in Induction of Beta Cell Apoptosis Tamara Cvjetićanin 1 , Ivana Stojanović, Gordana ... T Cells Cooperate With Palmitic Acid in Induction of Beta Cell Apoptosis Tamara Cvjetićanin et al. BMC Immunol. 2009 ...
... in pancreatic cell line NIT-1 and its effect on cell apoptosis after binding with erythropoietin (EPO), NIT-1 cells were ... Presently, the effects of resistin on rat insulinoma cells RINm5F were examined. Treatment of RINm5F with resistin induced cell ... on the apoptosis of Raji cells induced by sodium butyrate. The apoptosis of Raji cells were induced by sodium butyrate for 2, 4 ... The odontoblast-like cells were prepared from the pulp cells of rat incisors. Apoptosis was detected by measuring caspase-3 ...
... and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those ... Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic β cell apoptosis, we ... When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In ...
... serine phosphorylation of IRS-1 and apoptosis in rat insulinoma cells. ... Cell. 2015 Jan 15;160(1-2):20-35. doi: 10.1016/j.cell.2014.12.003. Epub 2014 Dec 18. Review. ... T cell-positive selection uses self-ligand binding strength to optimize repertoire recognition of foreign antigens. ... Cell Stress Chaperones. 2012 Jul;17(4):517-21. doi: 10.1007/s12192-012-0327-5. Epub 2012 Feb 10. ...
Cell cultures. Rat insulin-secreting INS-1E cells (passage 15-30; a kind gift from C. B. Wollheim, University of Geneva, ... Palmitate selectively augmented p66 Shc mRNA and protein expression approximately threefold also in rat insulinoma INS-1E cells ... Palmitate-induced apoptosis involves p66Shc. Exposure of INS-1E cells to palmitate raised the proportion of apoptotic cells ... Measurements of apoptosis. Apoptosis was measured by evaluating mono- and oligonucleosomes in the cytoplasmic fraction of cell ...
Nix induces programmed cell death in cultured insulinoma cells.. Recent studies have implicated Nix as a transcriptionally ... Nix induces 2 mitochondrial cell death pathways, apoptosis and programmed necrosis, in Pdx1-deficient β cells. Not only do ... mice had normal β cell area and β cellcell ratio, with normal islet architecture of a central core of β cells surrounded by ... mRNA from 3 independent wells of MIN6 cells infected with Pdx1 shRNA was compared with control infected cells. MIN6 cell cDNA ...
D) Rates of β cell apoptosis as assessed by TUNEL. For sections containing TUNEL/insulin double positive cells, cell death was ... by examining the consequences of an acute reduction in Pdx1 expression on the UPR in the Min6 mouse insulinoma β cell line. ... 2008) Crucial roles of neuronatin in insulin secretion and high glucose-induced apoptosis in pancreatic beta-cells. Cell Signal ... Indeed, HF-feeding resulted in a 4-fold increase in β cell apoptosis only in Pdx1+/− mice (Fig. 2D). Further, although β cell ...
apoptosis. Reduced pancreatic β-cell number and function characterize all forms of diabetes. Insulin-secreting β cells are ... that ATF5 regulates β-cell viability in the immortalized Min6 insulinoma cell line in response to stress caused by high cell ... ATF5 expression in β cells is stress inducible, and ATF5 deficiency results in a significant increase in β-cell apoptosis in ... 2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52(1):102-110. ...
Lee, H. S., Jeong, J., and Lee, K. J. (2009). Characterization of vesicles secreted from insulinoma NIT-1 cells. J. Proteome ... In this study, the authors isolated by differential centrifugation exosome and microvesicles from a rat insulinoma cell line ( ... NHI 6F Tu28). Exosome and microvesicles were derived from β-cells after cytokine induced apoptosis. EVs proteins were digested ... An initial study looked at exosomes isolated from NT1 insulinoma cell lines using differential centrifugation. The proteome ...
Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells. ... Berberine Induces Cell Apoptosis through ...
SOCS-3 overexpression also inhibited apoptosis induced by cytokines in primary β-cells. Lastly, we demonstrated that SOCS-3 ... Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we ... Department of Medical Cell Biology On the subject. Clinical Science Search outside of DiVA. GoogleGoogle Scholar. ... Both animal models for T1D as well as β-cell preparations exposed in vitro to putative noxious conditions were examined. ...
Cells bearing mutations causing Lebers hereditary optic neuropathy are sensitized to Fas-Induced apoptosis. J Biol Chem 277(8 ... to bisphenol A induces dysfunction of insulin secretion and apoptosis through the damage of mitochondria in rat insulinoma (INS ... After incubation, cells were rinsed twice with PBS, lysed with Promega cell lysis buffer, and shaken for 20 min at room ... Cell-Based ER-Mediated Bioassay. Recombinant human breast carcinoma cells (VM7Luc4E2, ERalpha-positive) were grown and ...
... is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. ... Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the ...
... gel filtration chromatography and RP-HPLC to obtain a cancer cell growth inhibitory peptide. Cell cycle distribution, Annexin V ... CTLEW induced both apoptosis and autophagy on MCF-7 cells, inhibited the cancer cells growth of Caco-2 and HeLa significantly, ... These results suggested that a novel bio-peptide, CTLEW inducing apoptosis and autophagy on MCF-7 cells can be released from ... western blot and immunofluorescence for LC3-II assay were used to detect apoptosis and autophagy on cells. Cytokine production ...
Mice deficient for PHD2 in several cell lineages, including EPO-producing cells, osteoblasts, and hematopoietic cells (CD68:cre ... In MIN6 cells, on the other hand, hypoxia led to a twofold (p < 0.01) increase in caspase-3 activity, an indicator of apoptosis ... When exposed to hypoxia, mouse insulinoma cells (MIN6) had an increased HIF-1alpha protein level, whereas its mRNA level did ... Upregulation of HIF-1alpha mRNA was also observed in D6 cells but not in P34 cells. Thus, the high-metastatic cells produced a ...
Growth inhibition and apoptosis of neuroblastoma cells through ROS-independent MEK/ERK activation by sulforaphane: Y.C. Hsu, et ... Measurement of total ROS/Superoxides in a rat insulinoma cell line using microplate reader, Abstract; Full Text ... Nilotinib induces ER stress and cell death in H9c2 cells: D. Lekes, et al.; Physiol. Res. 65, S505 (2016), Application(s): ... Reduction of connexin36 content by ICER-1 contributes to insulin-secreting cells apoptosis induced by oxidized LDL particles: J ...
MicroRNAs are master regulators of cell networks, but only scanty data are available on their transcriptome in these cells and ... and miR-298-5p raised the propensity to apoptosis of transfected and cytokine-treated αTC1-6 cells with respect to αTC1-6 cells ... is a major determinant of mammalian pancreatic α cells resistance to apoptosis induction by cytokines. ... cells: their comparison demonstrated significant differences. We also characterized the alterations of αTC1-6 cells microRNA ...
Both apoptosis and necrosis of β cells are mechanistically implicated in diabetes in these mice, but a molecular link between ... In this study, we introduced an shRNA into mouse insulinoma MIN6 cells to deplete Pdx1 and found that expression of ... These results establish Nix as a critical mediator of β cell apoptosis and programmed necrosis in Pdx1-deficient diabetes. ... Forced Nix expression in MIN6 and pancreatic islet β cells induced programmed cell death by simultaneously activating apoptotic ...
Cell-to-cell contact influences proliferative marker expression and apoptosis in MIN6 cells grown in islet-like structures. Am ... E and F, TGF-βi reduces caspase activation in cytokine-stimulated β-cells. Mouse insulinoma NIT-1 cells were stably transfected ... Cell-cell interaction is probably equally essential for β-cell function, as insulin-secreting MIN6 cells show significantly ... Both E-cadherin and N-cadherin are implicated in β-cell/β-cell and β-cell/non-β-cell interactions. The former is expressed on ...
... as GLP-1 reduced peroxide-induced apoptosis in Min6 insulinoma cells (84) and exendin-4 significantly attenuated cytokine- ... GIP does promote β-cell proliferation and cell survival in islet cell line studies (26,27); whether GIP also induces β-cell ... Hui H, Nourparvar A, Zhao X, Perfetti R: Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′- ... Drucker DJ: Glucagon-like peptides: regulators of cell proliferation, differentiation and apoptosis. Mol Endocrinol 17:161-171 ...
D. Choil and M. Wool, "Executioners of apoptosis in pancreatic β-cells: not just for cell death," American Journal of ... In an in vitro and in vivo model of insulinoma cells performed in rats (MIN6) with deficiency of the pancreatic and duodenal ... S. Fulda, "Alternative cell death pathways and cell metabolism," International Journal of Cell Biology, vol. 2013, Article ID ... "Endoplasmic reticulum stress sensitizes pancreatic beta cells to interleukin-1β-induced apoptosis via Bim/A1 imbalance," Cell ...
Cell Culture. INS-1 cells (Bioleaf Biotech Co., Ltd., Shanghai, China), derived from a rat insulinoma, were cultured in RPMI ... c) Ghrelin protects INS-1 cells from dexamethasone-induced cell apoptosis. INS-1 cells were incubated in complete medium ( ... Our data showed that ghrelin (0.1 μM) inhibited dexamethasone-induced (0.1 μM) apoptosis of INS-1 cells and facilitated cell ... Moreover, INS-1 cell apoptosis was not affected when cells were treated with U0126 or SB203580 alone (Figure 5(e)). These ...
  • These genes were able to protect NIT-1 cells from cytokine-induced apoptosis to varying degrees ranging from no protection to significant protection equivalent to an optimal dose of a chemical caspase inhibitor. (elsevier.com)
  • C/EBPδ overexpression decreases BIM expression and partially protect INS-1E cells against cytokine-induced apoptosis.INS-1E cells were left untransfected (grey bars) or transfected with pCMV-Ctrl (white bars) or pCMV-C/EBPδ (black bars) and subsequently left untreated or treated with IL-1β+IFN-γ for 16 or 24 h as indicated. (nih.gov)
  • Therefore, with respect to the potential impact of Reg3α on pancreatic islets and the fact that Reg3α plays an important role in tissue regeneration and inflammation, we hypothesized that elevated Reg3α production locally in islet grafts would protect islets from inflammatory cytokine-induced apoptosis, contribute to improved preservation of islet mass and better glycemic control in transplants. (springer.com)
  • Expressing a dominant-negative allele of Foxo1 reduces expression of apoptotic and ER stress markers and promotes β-cell survival from fatty acid and ER stress, identifying a potential therapeutic target for preserving β-cells in type 2 diabetes. (diabetesjournals.org)
  • We identify a previously unknown function for activating transcription factor 5 (ATF5) in the apoptotic susceptibility of β cells. (pnas.org)
  • However, suppression of apoptosis by the inclusion of a second transgene, the anti-apoptotic Bcl XL , results in a massive growth response and the production of large hyperplastic tumours - insulinoma. (warwick.ac.uk)
  • This review will discuss SOCS proteins as central regulators for diverse cellular processes important for normal β-cell function as well as their protective anti-apoptotic effects during β-cell stress. (frontiersin.org)
  • The transplantation of pancreatic islets for the treatment of type I diabetes is hindered by the enormous loss of cells due to early apoptotic events. (elsevier.com)
  • Sarkar SA, Kutlu B, Velmurugan K, Kizaka-Kondoh S, Lee CE, Wong R, Valentine A, Davidson HW, Hutton JC, Pugazhenthi S: Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor kappa-B (NF-κB) signaling in human islets and in a mouse beta cell line. (coh.org)
  • The transcription factor C/EBP delta has anti-apoptotic and anti-inflammatory roles in pancreatic beta cells. (nih.gov)
  • Trimerization of the death domains leads to the recruitment and activation of Fas-associated death domain protein, which promotes transmission of an apoptotic signal and induces apoptosis via both the extrinsic and intrinsic mitochondrial pathways [ 6 , 8 , 9 ]. (ijbs.com)
  • However, evidence indicates that cancer cells can develop resistance to TRAIL if they lose the ability to express death receptors or exhibit constant activation of anti-apoptotic pathways [ 9 , 10 ]. (ijbs.com)
  • Thapsigarin-treated INS-1 cells exhibited an increase in the ratio of BCL-x(s) (pro-apoptotic) to BCL-x(L) (anti-apoptotic) but BEL prevented this shift in splicing. (vcu.edu)
  • Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting from apoptotic destruction of β cells in the islets of Langerhans. (rupress.org)
  • Although multiple mechanisms are involved in the destruction of β cells, the common unifying theme remains that most of these trigger the apoptotic machinery of the β cell ( 5 )( 6 ). (rupress.org)
  • INS-1 cells had been cultured in the existence or lack of BPA (0.0020-2.0?was mixed up in apoptotic procedure induced by BPA. (expandingmarketing.com)
  • The expression of GLP-1 by -cells reduced the number of apoptotic cells and increased the expression of the antiapoptotic protein Bcl-2. (gembio.com)
  • Indeed, these nanosized membrane vesicles transmit EV-mediated signals by proteins, lipids, nucleic acids and sugars, and the unique molecular pattern of this package dictate the type of extracellular signal to be transmitted to recipient cells. (frontiersin.org)
  • Moreover, considerable evidence has demonstrated that dexamethasone causes apoptosis of islet cells [ 2 , 6 ], which is implicated in the activation of glucocorticoid receptors and calcineurin, and causes an imbalance in the anti- and proapoptotic proteins Bcl-2 and BAD, respectively. (hindawi.com)
  • Also, mutations in many genes encoding secretory proteins cause these proteins to fold improperly, thereby generating chronic ER stress and leading to cell degenerative diseases. (pubmedcentralcanada.ca)
  • Suppressors of cytokine signaling (SOCS) are a family of eight proteins that negatively regulate Janus kinase and signal transducers and activators of transcription signaling in cells that utilize this pathway to respond to extracellular stimuli. (frontiersin.org)
  • The growth of cells within the body is carefully mediated by the precise interactions of a variety of proteins. (warwick.ac.uk)
  • Proteins are involved in most cellular processes, and it is thus expected that their cumulative expression profile reflects the specific activity of cells. (mcponline.org)
  • Cells had been transduced with adenoviruses expressing individual or rat preproIAPP-EGFP r-IAPP or (h-IAPP, respectively) or green fluorescein proteins (GFP) at multiplicity of infections (MOI)? (welbourneprimary.com)
  • One way to achieve successful islet transplantation for the treatment of IDDM would be to genetically engineer β cells to express antiapoptotic and antiinflammatory proteins ( 24 ). (rupress.org)
  • Ghrelin has been shown to exert a protective effect in both human islet and β cells, inhibit cell apoptosis, and modulate the expression of genes that are essential in pancreatic islet cell biology [ 14 , 15 ]. (hindawi.com)
  • There was a significant reduction in the expression of numerous cell cycle genes from the late G1 phase through the M phase, and cells were arrested at the G1/S checkpoint. (elsevier.com)
  • Genetic engineering of islets with cytoprotective genes is an important strategy aimed to enhance the survival of these cells in the transplant setting. (elsevier.com)
  • The present study was designed to evaluate and compare the effects of five genes on a cell line derived from insulin-producing β-cells, NIT-1. (elsevier.com)
  • We conducted a high-throughput RNA inhibition screen to knockdown gene expression levels of the four genes comprising the test (ARHGDIA, COBLL1, PKM2, TM4SF1) in both a human lung-derived normal and a tumor cell line using three different small inhibitory RNA molecules per gene. (biomedcentral.com)
  • Knockdown of ARHGDIA, COBLL1, and TM4SF1 resulted in 2- to 4-fold increased levels of apoptosis in normal cells (ARHGDIA only) and tumor cells (all three genes). (biomedcentral.com)
  • Antibodies against double-stranded dna and rna, divide by the involvement of the mhc class ii genes is required for anti-apoptosis function. (hemsleyandhemsley.com)
  • subunit 6 of the mitochondrial ATP synthase) and (one of the genes coding for enzymes involved in rate-limiting steps of the TCA cycle) was significantly decreased in cells exposed to 0.020-2.0?and upregulation of were observed in BPA-exposed cells. (expandingmarketing.com)
  • This issue has been made more complex as 3 mechanistically distinct pathways to programmed β cell death have been observed in murine Pdx1 haploinsufficiency, apoptosis ( 11 - 14 ), autophagy ( 15 ), and programmed necrosis ( 16 ). (pubmedcentralcanada.ca)
  • Parallel pathways to β cell death offer an explanation for intermediate phenotypes obtained when individual death pathways have been targeted in Pdx1 -haploinsufficient mice ( 15 , 16 ). (pubmedcentralcanada.ca)
  • The molecular basis by which relative insufficiency of Pdx1 , a transcription factor that directs embryonic pancreatic growth and differentiation, induces multiple pathways of β cell death is not known. (pubmedcentralcanada.ca)
  • Finally, by examining β-cells overexpressing Suppressor of cytokine signalling 3 (SOCS-3) it was found that this could inhibit IL-1β induced signalling through the NF-κB and MAPK pathways. (diva-portal.org)
  • This can often lead to excessive growth, with cells no longer controlled by regular signalling pathways. (warwick.ac.uk)
  • Silibinin has been shown to suppress interleukin (IL)-1β and interferon (IFN)-γ-induced nitric oxide (NO) production and ameliorate β cell dysfunction through the suppression of c-Jun NH 2 -terminal kinase (JNK)/signal transducer and activator of transcription (STAT) pathways ( 14 ). (spandidos-publications.com)
  • We show in the present report that after a 1-hour preincubation of MLTC-1 Leydig cells with FLX, the intracellular cyclic adenosine monophosphate (cAMP) responses to Luteinizing Hormone (LH) and forskolin (FSK) are reduced through AMPK-dependent and -independent pathways respectively. (bvsalud.org)
  • Distinct pathways of cell migration and antiapoptotic response to epithelial injury: structure-function analysis of human intestinal trefoil factor. (embl-heidelberg.de)
  • It is believed that the conflicting effects depend on the cell type used, the cellular events following external stimuli, the duration of AMPK activation, and/or the pathways regulated downstream of AMPK. (nature.com)
  • We examined the mechanism of fatty acid-induced apoptosis of mouse β-cells especially as related to the role played by endoplasmic reticulum (ER) stress-induced Foxo1 activation and whether decreasing Foxo1 activity could enhance cell survival. (diabetesjournals.org)
  • Here, we find that Pdx1 is required for compensatory β cell mass expansion in response to diet-induced insulin resistance through its roles in promoting β cell survival and compensatory hypertrophy. (pnas.org)
  • The survival and function of insulin-secreting β cells is critical for the prevention of diabetes. (pnas.org)
  • Here we show that Atf5 , a close but less-studied relative of Atf4 , is also a target of Pdx1 and is critical for β-cell survival under stress conditions. (pnas.org)
  • Necroptosis, autophagy, and pyroptosis are molecular mechanisms that modulate the survival of the pancreatic beta cell, demonstrating the importance of the immune system in glucolipotoxicity processes and the potential role for immunometabolism as another component of what once known as the "ominous octet. (hindawi.com)
  • The ECM is certainly critical for the above-described phenomena, as its RGD motif can promote β-cell survival via signaling through α5β1 and αVβ3 on the β-cell surface ( 4 - 6 ). (jimmunol.org)
  • These findings suggest that measures preserving and promoting β-cell-ECM interaction and methods enhancing β-cell interactions with surrounding cells will likely ameliorate the survival and function of native and transplanted islets. (jimmunol.org)
  • We propose that divergent cell fates during ER stress hinge on a balance between IRE1α RNase outputs that can be tilted with kinase inhibitors to favor survival. (pubmedcentralcanada.ca)
  • Paradoxically, UPR signaling promotes opposite cell fates-adaptation/survival versus death-thereby acting as a switch. (pubmedcentralcanada.ca)
  • These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway. (aacrjournals.org)
  • ud This work brings into question the use of rapamycin as an immunosuppressant in islet transplantation and also highlights the key role of PKB in β cell survival. (core.ac.uk)
  • Consequently, inhibiting the manifestation of appoptosin may benefit pancreatic -cells survival during islet transplantation. (stopvivisection.info)
  • by contrast, overexpression of p66 Shc , but not that of the phosphorylation-defective p66 Shc mutant, enhanced palmitate-induced apoptosis. (springer.com)
  • Although TNF-α is one of the most important death effector molecules, most primary or immortalized cells are not susceptible to apoptosis by TNF-α alone because of the concomitant activation of the antiapoptotic process by TNF-α (8-10). (yonsei.ac.kr)
  • The effects of the FA palmitate on p66 Shc expression were evaluated in human and murine islets and in rat insulin-secreting INS-1E cells. (springer.com)
  • Through high-throughput real-time PCR, we analyzed the steady state microRNA transcriptome of murine pancreatic α (αTC1-6) and β (βTC1) cells: their comparison demonstrated significant differences. (biomedcentral.com)
  • The aim of this thesis was to establish the effects of rapamycin, one of the primary immunosuppressants used in islet transplantation, on murine β cells and islets and elucidate the mechanisms of any toxicity seen. (core.ac.uk)
  • The pancreas is a mixed gland formed by exocrine tissue represented by acinar cells that synthetize and secrete inactive digestive enzymes and by epithelial cells lining the small pancreatic ducts, which secrete great volumes of liquid rich in sodium and bicarbonate [ 1 ]. (hindawi.com)
  • Correa-Medina M, Bravo-Egana V, Rosero S, Ricordi C, Edlund H, Diez J, and Pastori RL: MicroRNA miR-7 is preferentially expressed in endocrine cells of the developing and adult human pancreas. (coh.org)
  • The pancreatic islets of Langerhans are small conglomerates of cells (on average 1,000 cells) with their own blood supply and neural innervations and are dispersed all over the pancreas embedded in the exocrine tissue. (mcponline.org)
  • The pancreas is a relatively inaccessible intra-abdominal (retroperitoneal) organ and the islet constitutes approximately 1% of the total pancreas cell mass. (mcponline.org)
  • Other Specific Types of Diabetes- For example, specific genetic defects of β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas, endocrinopathies, drug or chemically induced, infections, uncommon forms of immune-mediated diabetes, and other genetic syndromes sometimes associated with diabetes. (mcponline.org)
  • Pancreatic β-cell is considered as one of the most important cell types in the islet of Langerhans in pancreas. (biomedcentral.com)
  • Mitochondrial O 2 consumption and adenosine triphosphate (ATP) synthesis rates of osteosarcoma cybrid cells were measured before and after CPC and BAK treatment. (nih.gov)
  • A novel family of human mitochondrial RNAs, referred to as chimeric RNAs, which are differentially expressed in normal, pre-cancer and cancer cells, are described. (freepatentsonline.com)
  • In one embodiment of this invention, these oligonucleotides hybridize with the sense or with the antisense mitochondrial chimeric RNAs, and the result of the hybridization is useful to differentiate between normal proliferating cells, pre-cancer cells and cancer cells. (freepatentsonline.com)
  • Fiaschi-Taesch N, Bigatel TA, Sicari B, Takane KK, Salim F, Velazquez-Garcia S, Harb G, Selk K, Cozar-Castellano I, Stewart AF: Survey of the Human Pancreatic Beta Cell G1/S Proteome Reveals a Potential Therapeutic Role for Cdk-6 and Cyclin D1 in Enhancing Human Beta Cell Replication and Function in Vivo. (coh.org)
  • Ephrin-B2 is specifically expressed in arterial angioblasts, endothelial cells, and perivascular mesenchymal cells, whereas EphB4 is expressed in endothelial cells belonging to the venous lineage only. (biomedcentral.com)
  • MicroRNAs are master regulators of cell networks, but only scanty data are available on their transcriptome in these cells and its alterations in diabetes mellitus. (biomedcentral.com)
  • Our observations indicated that formononetin could protect against pancreatic β-cell apoptosis caused by IL-1β and therefore could be used in the future as a new drug improving diabetes mellitus. (mdpi.com)
  • We studied therapeutic activity of co-transplantation of allogeneic pancreatic islet cells and mesenchymal bone marrow progenitors on TiNi scaffolds in Wistar rats with experimental alloxan-induced diabetes mellitus. (bvsalud.org)
  • Type I insulin-dependent diabetes mellitus (IDDM) 1 is an autoimmune disease resulting from specific destruction of the insulin-producing β cell within the islet of Langerhans ( 1 )( 2 ). (rupress.org)
  • To this end, [Lys40(Ahx-DTPA-111In)NHExendin-4, a radiopeptide that selectively binds to GLP-1R expressed on insulinoma and other neuroendocrine tumor cells, was co-administered with PTK787, an inhibitor of vascular endothelial growth factors (VEGFR). (aacrjournals.org)
  • Because they faithfully recapitulate the human clinical phenotypes, Pdx1 -deficient mice have been widely used to characterize and define cellular mechanisms for β cell loss in diabetes. (pubmedcentralcanada.ca)
  • Understanding the role of ATF5 deepens our understanding of the complex mechanisms governing β-cell fate decisions, providing a potential pathway for the prevention of diabetes. (pnas.org)
  • Fluoxetine (FLX), a widely used antidepressant primarily acting as a selective serotonin reuptake inhibitor (SSRI), has been shown to exhibit other mechanisms of action in various cell types. (bvsalud.org)
  • FLX also inhibited hormone-induced steroidogenesis in MLTC-1 cells and mouse testicular Leydig cells, suggesting similar mechanisms in both cell types. (bvsalud.org)
  • Increasing our understanding of the extrinsic, as well as intrinsic, mechanisms that control these processes should facilitate efforts to regenerate this important cell type in humans. (biologists.org)
  • As autoimmunity can be the result of a breakdown in peripheral tolerance, determining the mechanisms that keep self-reactive T cells in check is important for understanding pathogenesis. (rupress.org)
  • In the current study, we observed the effects of two well-known AMPK activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin, on apoptosis in rat insulinoma INS-1E cells, and further explored their possible mechanisms. (umm.ac.id)