Dipeptidyl Peptidase 4: A serine protease that catalyses the release of an N-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including INCRETINS; NEUROPEPTIDES; and CHEMOKINES. The protein is also found bound to ADENOSINE DEAMINASE on the T-CELL surface and is believed to play a role in T-cell activation.Dipeptidyl-Peptidase IV Inhibitors: Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.Dipeptidyl-Peptidases and Tripeptidyl-Peptidases: A subclass of exopeptidases that includes enzymes which cleave either two or three AMINO ACIDS from the end of a peptide chain.Adamantane: A tricyclo bridged hydrocarbon.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.PyrrolidinesProtease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Cathepsin C: A papain-like cysteine protease that has specificity for amino terminal dipeptides. The enzyme plays a role in the activation of several pro-inflammatory serine proteases by removal of their aminoterminal inhibitory dipeptides. Genetic mutations that cause loss of cathepsin C activity in humans are associated with PAPILLON-LEFEVRE DISEASE.Blood Glucose: Glucose in blood.Antigens, CD13: Zinc-binding metalloproteases that are members of the type II integral membrane metalloproteases. They are expressed by GRANULOCYTES; MONOCYTES; and their precursors as well as by various non-hematopoietic cells. They release an N-terminal amino acid from a peptide, amide or arylamide.Dipeptidases: EXOPEPTIDASES that specifically act on dipeptides. EC 3.4.13.Gastric Inhibitory Polypeptide: A gastrointestinal peptide hormone of about 43-amino acids. It is found to be a potent stimulator of INSULIN secretion and a relatively poor inhibitor of GASTRIC ACID secretion.PyrazinesRolipram: A phosphodiesterase 4 inhibitor with antidepressant properties.Glucagon-Like Peptide 2: A 33-amino acid peptide derived from the C-terminal of PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. It stimulates intestinal mucosal growth and decreased apoptosis of ENTEROCYTES. GLP-2 enhances gastrointestinal function and plays an important role in nutrient homeostasis.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Glucagon-Like Peptides: Peptides derived from proglucagon which is also the precursor of pancreatic GLUCAGON. Despite expression of proglucagon in multiple tissues, the major production site of glucagon-like peptides (GLPs) is the INTESTINAL L CELLS. GLPs include glucagon-like peptide 1, glucagon-like peptide 2, and the various truncated forms.Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Dipeptides: Peptides composed of two amino acid units.Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Pyrrolizidine Alkaloids: A group of ALKALOIDS, characterized by a nitrogen-containing necine, occurring mainly in plants of the BORAGINACEAE; COMPOSITAE; and LEGUMINOSAE plant families. They can be activated in the liver by hydrolysis of the ester and desaturation of the necine base to reactive electrophilic pyrrolic CYTOTOXINS.TriazolesPhosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.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.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.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.Hypoglycemic Agents: Substances which lower blood glucose levels.Chemokine CCL8: A monocyte chemoattractant protein that attracts MONOCYTES; LYMPHOCYTES; BASOPHILS; and EOSINOPHILS. Chemokine CCL8 has specificity for CCR3 RECEPTORS and CCR5 RECEPTORS.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Phosphodiesterase 4 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 4.Angioedema: Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.Pentanoic AcidsRats, Inbred F344Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Pyrrolidinones: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)Peptide YY: A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion.Isoflurophate: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.ThiazolesOligopeptides: Peptides composed of between two and twelve amino acids.Swainsonine: An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Cyclic Nucleotide Phosphodiesterases, Type 4: A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Glucagon: A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)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.Glucose Tolerance Test: A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Incretins: Peptides which stimulate INSULIN release from the PANCREATIC BETA CELLS following oral nutrient ingestion, or postprandially.Kinetics: The rate dynamics in chemical or physical systems.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).Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.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.Rats, Zucker: Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene.