TY - JOUR. T1 - A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine. AU - Dixon, G. AU - Nolan, J. AU - McClenaghan, Neville. AU - Flatt, Peter. AU - Newsholme, P. PY - 2003/12. Y1 - 2003/12. N2 - Evidence has been published that L-alanine may, under appropriate conditions, promote insulin secretion in normal rodent islets and various beta cell lines. Previous results utilising the clonal beta-cell line BRIN-BD11, demonstrated that alanine dramatically elevated insulin release by a mechanism requiring oxidative metabolism. We demonstrate in this paper that addition Of L-alanine had an insulinotropic effect in dispersed primary islet cells. Addition Of D-glucose increased L-alanine consumption in both BRIN-BD11 cells and primary islet cells. L-glutamine consumption in the BRIN-BD11 cell line and primary rat islets was also determined. The consumption rate was in line with that previously reported for ...
The proliferative response of non-β islet endocrine cells in response to type 1 diabetes (T1D) remains undefined. We quantified islet endocrine cell proliferation in a large collection of non-diabetic control and T1D human pancreata across a wide range of ages. Surprisingly, islet endocrine cells with abundant proliferation were present in many adolescent and young adult T1D pancreata. But, the proliferative islet endocrine cells were also present in similar abundance within control samples. We queried the proliferating islet cells with antisera against various islet hormones. Although PP, somatostatin, and ghrelin cells did not exhibit frequent proliferation, glucagon-expressing α-cells were highly proliferative in many adolescent and young adult samples. Notably, α-cells only comprised a fraction (∼1/3) of the proliferative islet cells within those samples; most proliferative cells did not express islet hormones. The proliferative hormone negative cells uniformly contained ...
The proliferative response of non-β islet endocrine cells in response to type 1 diabetes (T1D) remains undefined. We quantified islet endocrine cell proliferation in a large collection of non-diabetic control and T1D human pancreata across a wide range of ages. Surprisingly, islet endocrine cells with abundant proliferation were present in many adolescent and young adult T1D pancreata. But, the proliferative islet endocrine cells were also present in similar abundance within control samples. We queried the proliferating islet cells with antisera against various islet hormones. Although PP, somatostatin, and ghrelin cells did not exhibit frequent proliferation, glucagon-expressing α-cells were highly proliferative in many adolescent and young adult samples. Notably, α-cells only comprised a fraction (∼1/3) of the proliferative islet cells within those samples; most proliferative cells did not express islet hormones. The proliferative hormone negative cells uniformly contained ...
The pancreatic islets are collections of endocrine cells, dispersed throughout the pancreas. In adult islets, endocrine cells are closely associated with capillary endothelial cells and receive a high blood perfusion. Transplanted pancreatic islets, on the other hand, have a vascular disturbance, manifested as decreased blood vessel density. Besides impaired islet blood perfusion and oxygenation, this means that the normal close proximity between endothelial cells and β-cell in adult islets is interrupted. The aim of the thesis was to investigate if, and to what extent, β-cells and islet endothelial cells can interact with one another. This hypothesis was investigated during physiological growth of pancreatic islets, following transplantation and in vitro. We observed that islet endothelial and endocrine cell replication coincided immediately after birth, as well as during pregnancy. In pregnant animals, β-cell proliferation colocalized to islets with increased endothelial cell replication, ...
The fluorescent probe SBFI was used to monitor the influence of acetylcholine (ACh) on the cytosolic concentration of free Na+ (Na+i) in single mouse pancreatic B-cells. In the presence of 3 mM glucose and 135 mM extracellular Na+, Na+i averaged 16.6 mM. ACh (100 microM) increased Na+i by approximately 80%. This rise was prevented by atropine, a blocker of muscarinic receptors, and by omission of extracellular Na+, but still occurred if the sodium pump was blocked by ouabain. It was unaffected by tetrodotoxin, a blocker of voltage-sensitive Na+ channels, and was not mimicked by depolarization of the cells with high K+. It is concluded that activation of muscarinic receptors increases the membrane permeability to Na+ in pancreatic B-cells. ...
In the present study, we demonstrated the protein expression of three PDK isoforms (PDK1, PDK2, and PDK4) in rat pancreatic islets (no sufficiently specific antibodies are as yet available for PDK3). We also showed, for the first time, that the PDK isoform protein expression profile of rat pancreatic islets is selectively modified in response to prolonged starvation. A major novel finding is that PDK1 and (to a lesser extent) PDK2 protein expression in the rat pancreatic islet is suppressed by prolonged starvation, whereas the protein expression of the third PDK isoform, PDK4, is specifically upregulated by starvation. We also demonstrated, for the first time, specific upregulation of PDK4 and PPAR-α protein expression in rat pancreatic islets in response to the administration of the PPAR-α agonist WY14,643, identifying a potential role for PPAR-α-linked functions in the islet response to starvation. We analyzed the impact of antecedent changes in islet PDK protein expression and PPAR-α ...
Many GTP-binding proteins (GBPs) are modified by mevalonic acid (MVA)-dependent isoprenylation, carboxyl methylation or palmitoylation. The effects of inhibitors of these processes on insulin release were studied. Intact pancreatic islets were shown to synthesize and metabolize MVA and to prenylate several candidate proteins. Culture with lovastatin (to inhibit synthesis of endogenous MVA) caused the accumulation in the cytosol of low-M(r) GBPs (labelled by the [alpha-32P]GTP overlay technique), suggesting a disturbance of membrane association. Concomitantly, lovastatin pretreatment reduced glucose-induced insulin release by about 50%; co-provision of 100-200 microM MVA totally prevented this effect. Perillic acid, a purported inhibitor of the prenylation of small GBPs, also markedly reduced glucose-induced insulin secretion. Furthermore, both N-acetyl-S-trans, trans-farnesyl-L-cysteine (AFC), which inhibited the base-labile carboxyl methylation of GBPs in islets or in transformed beta-cells, ...
Effect of rapamycin on pancreatic islet morphology in NONcNZO10 mice.(A) Islet numbers and size variability do not differ between untreated and rapa-treated gro
Aims: To test whether the immersion of the pancreas in solutions of 1 or 2 mg/mL of collagenase in 4°C for 24 hours, for the isolation of Langerhans islets, rises the yield of islets/grams of pancreatic tissue. Methods: Experimental study with mouses, performed in the Laboratory of Nephrology of the Instituto de Pesquisas Biológicas do Hospital São Lucas da PUCRS, Porto Alegre, RS. After the animals have been sacrified under anesthesia, the pancreas were removed and divided in four groups, according the technique used for isolating the islets. A) collagenase 1mg/mL, in 4ºC for 24 hours and heating for 39ºC for 15 minutes. B) collagenase 2mg/mL with the same previous described steps. C) collagenase 1mg/mL and heating of the solution in the same day, in 39ºC for 15 minutes. D) collagenase 2mg/mL and heating of the solution in the same day, in 39ºC for 15 minutes. We verified the viability of the islet through the trypan blue test. Results: The median numbers of isolated islets in the groups ...
Inhibitory effects on glucose-induced insulin secretion by previous palmitate were additive to the inhibitory effects exerted by previous high glucose (11 and 27 mmol/l). Palmitate-induced inhibition of insulin secretion was evident after exposure to 25 μmol/l added fatty acid. The insulin content of islets exposed to fatty acids was significantly reduced, and glucose-induced proinsulin biosynthesis was inhibited by 59% after palmitate addition and by 51% after oleate exposure (P,0.01). These effects were partly prevented by etomoxir (P,0.05). The activity of PDH in mitochondrial extracts of islets preexposed for 48 h to palmitate was decreased by 35% (P,0.05) υs. that in control islets, whereas the activity of PDH kinase (which inactivates PDH) was significantly increased in the same preparations (P,0.05 ...
ADDITIONAL INFORMATION FOR POTENTIAL APPLICANTS TO THE HUMAN PANCREATIC ISLET CELL RESOURCE CENTER (ICR) COOPERATIVE AGREEMENT Release Date: February 5, 2001 NOTICE: NOT-RR-01-004 National Center for Research Resources (http://www.ncrr.nih.gov) National Institute of Diabetes and Digestive and Kidney Diseases (http://www.niddk.nih.gov) Juvenile Diabetes Research Foundation International (http://www.jdf.org) This notice is an addendum to RFA-RR-01-002, entitled "HUMAN PANCREATIC ISLET CELL RESOURCE CENTER (ICR)", which was previously published as Request for Applications RR-01-002 in the NIH Guide for Grants and Contracts (https://grants.nih.gov/grants/guide/rfa-files/RFA-RR-01-002.html). The listing of FDA guidance documents and information relevant to this RFA has been expanded to include: CELL/TISSUE BASED DOCUMENTS o "Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy" (1998) available at: http://www.fda.gov/cber/gdlns/somgene.pdf o "Points to Consider in the ...
Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which T-cells and macrophages invade the islets of Langerhans and selectively destroy the insulin producing β-cells, either directly or through the secretion of e.g. cytokines and nitric oxide (NO). This thesis has studied possible strategies to prevent T1DM. In β-cells and macrophages, NO is produced by inducible nitric oxide synthase (iNOS). In the first study, we found that 1400W, a highly selective inhibitor of iNOS could prevent interleukin (IL)-1β induced suppression of rat islet function in vitro, but not diabetes induced by multiple low dose streptozotocin (MLDS), a well established animal model for autoimmune diabetes, in vivo. Next, we wanted to test a new type of high affinity blocker of IL-1 action, called IL-1 trap, in vitro. Here we found that an IL-1 trap could prevent the suppressive effects by IL-1β on rat pancreatic islet function. Also, it was sufficient to block the action of IL-1β to prevent islet cell death ...
The analysis of T-cell responses to islet proteins using the CI assay has allowed us to identify, in cross-sectional studies, cellular islet autoimmunity in T1D (21-23,25), in subjects at risk for T1D (24), and in phenotypic T2D patients (26-30). The presence of islet-specific cellular autoimmunity in T2D patients was also recently confirmed by an independent laboratory (35). However, longitudinal studies investigating islet autoimmune development in T2D patients have been lacking.. In this study, we observed development of islet autoimmunity, measured by islet Abs and islet-specific T-cell responses, in 61% of the phenotypic T2D patients. We also observed a significant association between positive islet-reactive T-cell responses and a more rapid decline in β-cell function as assessed by FCP and glucagon-SCP responses. Moreover, the high percentage (30%) of Ab−T+ T2D patients observed in this study supports our previously published cross-sectional observations and demonstrates the importance ...
In this study, we identified TGF-βi as a vital trophic factor for islet β-cells. It enhanced islet survival and function both in vitro and in vivo. Of greater interest, it seemed to be able to induce islet neogenesis, which resulted in insulin-positive cell clusters in young mice and giant islets in older mice.. TGF-βi can function as "glue" between the ECM and cells: it can attach to collagen in ECM through one or more of its four FAS1 domains and attach cells via integrins to its remaining FAS1 domain as well as its C-terminal RGD domain. In addition, TGF-βi can also function as glue between cells: it can hold different cells together with its four FAS1 domains and RGD domain, all of which can interact with various integrins on the cell surface. This is likely the mechanism by which recombinant and Tg TGF-βi conferred better islet integrity during culture.. β-cells in islets need trophic factors to survive and function, both in vivo and in vitro. Isolated islets gradually die in culture. ...
Foetal islets are functionally immature but retain their capacity for proliferation if harvested and cultured in an appropriate manner. Graft function was shown to depend largely on the gestational age and conditions of organ culture prior to transplantation. The required period of organ culture for optimal graft function was investigated for foetal mouse pancreas of different gestational ages. The growth of the graft in situ also depended on the diabetic state of the host, and chronic hyperglycaemia appeared to impair graft function. Subsequent studies using NOD recipient mice as a model for IDDM showed that recurrent autoimmune disease was seen in foetal islet isografts but rapid rejection of allografts and foetal pig xenografts also occurred. The striking differences seen between the allo-, and xenograft response was the presence of many eosinophils that dominated the infiltrate at the xenograft site. However, HAR was not a problem in this discordant xenograft and Gal(1-3)Gal expression, the ...
DESCRIPTION (provided by applicant): Transplantation of human islets has great potential as an effective means of treating insulin dependent diabetes mellitus. Primary non-function is the main cause of islet graft failure and it results in the need for multi-donor transplants. We will test the hypothesis that islet engraftment can he enhanced simultaneously by expressing growth factor gene like human Vascular Endothelial Growth Factor (hVEGF) that promotes islet revascularization, and antiapoptotic gene like human interleukin-1 receptor antagonist (hIL-IRa) to prevent apoptosis of transplanted islets in the host. In preliminary studies, higher levels of hVEGF were secreted from human islets transfected with bicistronic adenoviral vector encoding hVEGF and Green Fluorescent Protein (Acv-GFP-hVEGF), while hVEGF secretion from Adv-GFP transfected and mock-transfected islets was very low. Insulin release from transfected islets was comparable to mock-transfected islets. Proapoptotic cytokines ...
We present several pieces of experimental evidence that IGRP-specific effector-memory CD8+ T cells in the peripheral lymphoid tissue of NOD mice have emigrated from islets. First, the T cell number in the periphery correlated with the severity of islet pathology and was reduced in mutant strains of NOD mice with reduced islet pathology but normal pancreatic lymph node T cell priming. Second, transferred naive T cells acquired effector memory phenotype in the islets, after exit from the pancreatic lymph node, and the peripheral T cells displayed a phenotype similar to that acquired in islets. Finally, islet-infiltrating T cells emigrated from islets transplanted into syngeneic, but immunodeficient NOD mice, were found in the peripheral lymphoid organs and invaded the native pancreas and caused diabetes, indicating that this chain of events can occur. We suggest that this also can occur from native, untransplanted islets. In T1D, we suggest that islet pathology results in proliferation and ...
In the pancreas of T1D patients, the immune system selectively destroys β cells in a process known as insulitis (12). Recently, immune cells have also been demonstrated to infiltrate the pancreata of T2D patients (10-14). In T1D, an autoimmune reaction characterizes the insulitis, whereas a more "autoinflammatory" infiltrate appears to characterize the insulitis associated with T2D (10-14). Moreover, islet-reactive T cells responding to multiple islet proteins have been found in both T1D patients (15-18) and phenotypic T2D patients with and without islet autoantibodies, the historical hallmark of islet autoimmunity (19-22). Potential differences between T1D patients and autoimmune phenotypic T2D patients in the islet proteins recognized by T cells have been identified, hinting at potentially different pathogenic mechanisms (21). These studies suggest that T-cell-mediated islet damage may be a component of more than just classic T1D. Recently, we demonstrated in phenotypic T2D patients that the ...
Enhanced expression of chemotactic cytokines (aka chemokines) within pancreatic islets likely contributes to islet inflammation by regulating the recruitment and activation of various leukocyte populations, including macrophages, neutrophils, and T-lymphocytes. Because of the powerful actions of these chemokines, precise transcriptional control is required. In this review, we highlight what is known about the signals and mechanisms that govern the transcription of genes encoding specific chemokine proteins in pancreatic islet β-cells, which include contributions from the NF-κB and STAT1 pathways. We further discuss increased chemokine expression in pancreatic islets during autoimmune-mediated and obesity-related development of diabetes.
article{8523110, abstract = {Endothelial-endocrine cell interactions and vascular endothelial growth factor (VEGF)-A signalling are deemed essential for maternal islet vascularisation, glucose control and beta cell expansion during mouse pregnancy. The aim of this study was to assess whether pregnancy-associated beta cell expansion was affected under conditions of islet hypovascularisation. Soluble fms-like tyrosine kinase 1 (sFLT1), a VEGF-A decoy receptor, was conditionally overexpressed in maternal mouse beta cells from 1.5 to 14.5 days post coitum. Islet vascularisation, glycaemic control, beta cell proliferation, individual beta cell size and total beta cell volume were assessed in both pregnant mice and non-pregnant littermates. Conditional overexpression of sFLT1 in beta cells resulted in islet hypovascularisation and glucose intolerance in both pregnant and non-pregnant mice. In contrast to non-pregnant littermates, glucose intolerance in pregnant mice was transient. sFLT1 overexpression ...
The beta cells are particularly important because they make insulin. Degeneration of the beta cells is the main cause of type I (insulin-dependent) diabetes mellitus.
Guanine nucleotide-binding proteins (G-proteins) are known to act as important modulators of insulin release from the islets of Langerhans. We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal α-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. With the use of isolated mouse islets the present investigation was performed in a primary attempt to elucidate whether this inhibitory mechanism in some way was linked to the β-cell G-protein system. Treatment of freshly isolated islets with pertussis toxin (PTX), which is known to inactivate the Gi-proteins, abolished the inhibitory effect of the α2-adrenoceptor agonist clonidine on insulin release stimulated by the phosphodiesterase inhibitor IBMX in the presence of the protein kinase C activator TPA and even changed it into an increase. Emiglitate did not display any inhibitory action on insulin release induced by these secretagogues. Similarly, ...
Guanine nucleotide-binding proteins (G-proteins) are known to act as important modulators of insulin release from the islets of Langerhans. We have recently found that the deoxynojirimycin-derivative emiglitate, a recognized inhibitor of intestinal α-glucosidehydrolase activity, is a powerful inhibitor of glucose-induced insulin release. With the use of isolated mouse islets the present investigation was performed in a primary attempt to elucidate whether this inhibitory mechanism in some way was linked to the β-cell G-protein system. Treatment of freshly isolated islets with pertussis toxin (PTX), which is known to inactivate the Gi-proteins, abolished the inhibitory effect of the α2-adrenoceptor agonist clonidine on insulin release stimulated by the phosphodiesterase inhibitor IBMX in the presence of the protein kinase C activator TPA and even changed it into an increase. Emiglitate did not display any inhibitory action on insulin release induced by these secretagogues. Similarly, ...
Pancreatic Islets: Almost 80 years ago, Dr. Frederick Banting published a report about use of pancreatic Islets to treat diabetes. He obtained those Islets from the pancreas of a dog. By first tying-off that pancreas, he eliminated the digestive enzymes that would otherwise have destroyed the insulin in the Islets.. Following the publication of that report, diabetics could hope for a way to replace the insulin lacking in their system. Biochemists were able to extract insulin from the pancreas of an animal. That insulin could then be prepared for injection into a diabetic patient. At that time, doctors could only dream about transplanting Islet cells into a diabetic patient.. Doctors have since learned that the Islets contain several types of cells. Among those various Islets cells, only the beta cells have the ability to make insulin. In the 1970s, a group of medical researchers began to look for a way to transplant beta cells into diabetic patients. Gradually, their research produced ...
Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1+/- mice compared with Pdx1+/+ littermate controls. Glucose sensing and islet Ca2+ responses were also normal. Depolarization-evoked exocytosis and Ca2+ currents in single Pdx1+/- cells were not different from controls, arguing against a ubiquitous β cell stimulus-secretion coupling defect. However, isolated Pdx1+/- islets and dispersed β cells were significantly more susceptible to apoptosis at basal glucose concentrations than Pdx1+/+ islets. BclXL and Bcl-2 expression were reduced in Pdx1+/- islets. In vivo, increased apoptosis was associated with abnormal islet architecture, positive TUNEL, active caspase-3, and ...
Within the pancreatic islet, the intra-islet vasculature plays a crucial role in pancreatic development, islet function and beta cell survival. We have shown that vascular endothelial cells are rapidly lost from isolated pancreatic islets during culture. Endothelial progenitor cells (EPCs) represent a potential cellular therapy that may replenish diminished intra-islet endothelial cell populations and improve the engraftment of transplanted pancreatic islets. In addition, EPCs may directly affect the function of pancreatic beta cells. In a diabetic murine syngeneic marginal mass islet transplant model we found that co-transplanted EPCs markedly improved the cure rate and initial glycaemic control of transplanted islets. Gene expression data indicate that EPCs, or their soluble products, modulate the expression of the beta cell surface molecule connexin 36, and affect glucose-stimulated insulin release. Using transwell co-cultures of MIN6 and MS-1 cell lines we have further examined the molecules ...
The various endocrine cell types present in mammalian Islets of Langerhans express a range of lipid-responsive G-proteln coupled receptors (GPCRs) including GPR119 and GPR120. These are each reported to be expressed In islet beta-cells and GPR 119 has been Implicated In the augmentation of glucose-stimulated insulin secretion by certain derivatives of long chain unsaturated fatty acids. By contrast GPR 120 does not appear to regulate insulin secretion and its role is unclear In addition to their ability to regulate hormone secretion long-chain fatty acids and their derivatives can also influence beta-cell viability but It IS unclear whether GPCRs are involved in mediating this response Therefore. the work undertaken in thesis has explored the possible involvement of GPR119 and GPR120 in the regulation of beta-cell viability. Long chain fatty acids exert differential effects on beta-cell viabilty according to their chain length and degree of unsaturation. Saturated molecules with chain lengths of ...
If doctors were able to place healthy, insulin-producing islets into a person with diabetes in a minimally invasive procedure that needs to be repeated only occasionally, diabetes care as we know it would be finished. Patients might occasionally need insulin, and would of course want to keep an eye on their blood glucose levels, but the often-grueling regimen many of us now follow would be a thing of the past.. What exactly is islet transplantation, anyway? In fact, what are islets?. What Are Islets?. Technically, theyre called the islets of Langerhans. These are clusters of cells that lie within the pancreas and produce insulin, glucagon and other hormones. When a person lacks beta cells, he or she also lacks a sufficient supply of these vital hormones, resulting in the condition we call diabetes.. Islets have been said to resemble fine golden sand, measuring about 1/4 millimeter in diameter, which makes them visible to the naked eye. Scientists can isolate islets from pancreatic tissue only ...
We used transplantation of human juvenile and adult islets into immunodeficient NSG mice (44, 45) to investigate mechanisms controlling human islet cell proliferation. Compared with retrospective studies of cadaveric pancreata or in vitro islet culture-based assays, this in vivo transplantation strategy afforded experimental flexibility, including relatively prolonged observation times, prospective exposure of islets to sequential or concurrent schedules of drugs, and serial measures of insulin secretion in response to Ex-4. In our transplantation model, the maintenance of greater levels of β cell proliferation after transplantation indicates that the proliferation resulted from intrinsic human islet cell signals, and was not dependent on the pancreatic environment or circulating human factors.. Recent studies suggest that insulin secretion by human islets may mature in an age-dependent manner (10), similar to findings in rodents (6-9). Using our transplant-based system, however, we found that ...
AIM/HYPOTHESIS: Increased expression of haeme-oxygenase 1 (HO1) and other antioxidant enzymes could improve pancreatic beta-cell survival under stressful conditions, including hyperglycaemia. However, how hyperglycaemia increases islet HO1 expression is not known. METHODS: Rat islets were pre-cultured for 1 week in RPMI medium containing 10 mmol x l(-1) glucose (G10), and further cultured overnight in G5-G30 plus various test substances. Islet HO1 mRNA and protein expression was measured by semiquantitative RT-PCR, western blot, and immunohistochemistry. RESULTS: Islet HO1 mRNA expression was minimal after overnight culture in G10, slightly increased in G5, and increased by five- to ten-fold in G30 in parallel with a heterogeneous increase in beta-cell HO1 protein expression. The effect of G30 was fully inhibited by agents decreasing cytosolic Ca2+ (diazoxide, nimodipine), but was only slightly reproduced by agents raising Ca2+ (tolbutamide, 30 mmol x l(-1) potassium). It was also suppressed by ...
BM stem cells may have regenerative effects on islet function through angiogenesis. Human islets (100islet equivalent/mL) were cultured alone (control) or co-cultured (experimental group) with whole human BM (1 × 10(6) cells/mL) for 210 days. A protein array measuring angiogenesis factors found upre …
After 50% proximal small bowel resection (SBR) in mice, we have demonstrated hepatic steatosis, impaired glucose metabolism without insulin resistance, and increased pancreatic islet area. We sought to determine the consequences of SBR on pancreatic ß-cell morphology, proliferation, and expression of a key regulatory hormone, glucagon-like peptide-1 (GLP-1). C57BL/6 mice underwent 50% SBR or sham operation. At 10 wk, pancreatic insulin content and secretion was measured by ELISA. Immunohistochemistry was performed to determine structural alterations in pancreatic α-and ß-cells. Western blot analysis was used to measure GLP-1R expression, and immunoassay was used to measure plasma insulin and GLP-1. Experiments were repeated by administering a GLP-1 agonist (exendin-4) to a cohort of mice following SBR. After SBR, there was pancreatic islet hypertrophy and impaired glucose tolerance. The proportion of α and ß cells was not grossly altered. Whole pancreas and pancreatic islet insulin content ...
Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing β-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackie B virus (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native β-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice
RESULTS: The GABA signalling system was compromised in islets from type 2 diabetic individuals, where the expression of the genes encoding the α1, α2, β2 and β3 GABA(A) channel subunits was downregulated. GABA originating within the islets evoked tonic currents in the cells. The currents were enhanced by pentobarbital and inhibited by the GABA(A) receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABA(A) channels (GABA(A) receptors) decreased both insulin and glucagon secretion. The GABA(B) receptor antagonist, CPG55845, increased insulin release in islets (16.7 mmol/l glucose) from normoglycaemic and type 2 diabetic individuals ...
Definition of islet cells in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is islet cells? Meaning of islet cells as a finance term. What does islet cells mean in finance?
I told him about my islet cell transplant and he seemed very interested. I explained to him that if my islets dont last forever, that maybe stem cells might help. I asked Dr. Caplan if he thought I had enough of my own islets left to repair and he didnt think so. I asked about the islet cell pouch procedure which could be loaded with stem cells. He thought that would probably not be available in time for me. He did say that he believed that my problem was not my islets dying off, but my long term exposure to the immunosuppressants. He strongly recommended that I ask my doctors about the possibility of a stem cell treatment. The stem cells have an immunosuppressive effect and could possibly allow me to lessen my current dose of immunosuppressive drugs. I said that I would ask about it, and I will. Now that I have had more time to think about it, I realize there would be complications with doing this. First of all, it would compromise my data for the study. I am still committed until my 3 year ...
TY - JOUR. T1 - Ca2+ transport in pancreatic βcells during glucose stimulation of insulin secretion. AU - Hellman, Bo. AU - Gylfe, Erik. AU - Berggren, Per Olof. AU - Andersson, Tommy. AU - Abrahamsson, Håkan. AU - Rorsman, Patrik. AU - Betsholtz, Christer. PY - 1980/1/1. Y1 - 1980/1/1. N2 - The role of Ca2+ in the regulation of insulin secretion was evaluated using βcell-rich pancreatic islets isolated from ob/ob-mice. The glucose stimulation of the secretory activity is supposed to result from accumulation of Ca2+ in the submembrane cytoplasmic space. It is likely that this process reflects the balance between increased entry of Ca2+ into the βcells and an enhanced sequestration of Ca2+ in the organelle sinks. The proposed model can explain the cAMP potentiation of glucose-stimulated insulin release with suppression of the mitochondrial Ca2+ uptake. Furthermore, differences in the Ca2+ buffering capacity of the secretory granules may account for other characteristic features of ...
In comparison with other cities, there are higher incidences in Chaoyang and Heyuan. Riboflavin-UVA-induced corneal samples of viagra and cialis collagen cross-linking in pediatric patients. A focus is placed on the pathophysiology and clinical presentation of respiratory muscle involvement in adults.. cremoris produced yellow colonies surrounded by yellow zones on this purple medium because of their ability to produce acid from lactose in the milk. Rfx6 is found in postmitotic islet progenitor cells in the embryo and is maintained in all developing and adult islet cell types. Tumor necrosis factor alpha induces human atrial myofibroblast tadalafil 20 mg best price proliferation, invasion and MMP-9 secretion: inhibition by simvastatin. The feasibility and effectiveness of emergency department based hypertension screening: a systematic review. According to the new signaling mechanism, a fluorescent probe for hypochlorite was then judiciously developed. Effect of generic cialis Irradiation on ...
There is a marked survival advantage for patients with nonsmall cell lung cancer (NSCLC) expressing high numbers of macrophages in their tumour islets. The primary aim of the present study was to determine the immunological phenotype of NSCLC-associated macrophages. CD68(+) macrophages expressing markers of a cytotoxic M1 phenotype or a noncytotoxic M2 phenotype were identified in the islets and stroma of surgically resected tumours from 20 patients with extended survival (median 92.7 months) and 20 with poor survival (median 7.7 months), using immunohistochemistry. The islet density of both M1 and M2 macrophages was markedly increased in extended compared with poor survival patients. In the extended survival group, M1 islet density was significantly increased compared with M2 density, 70% of islet macrophages were positive for M1 markers versus 38% for M2, and the islet:stromal ratio of M1 macrophages was markedly increased compared with M2. The 5-yr survival for patients with above and below ...
Zebrafish Islet1 is required for both SMN and PMN formation, and appears to mediate a switch between motoneuron and interneuron fates in the pMN domain. This apparently contrasts with the reported role of Islet1 in mouse, to promote motoneuron survival (Pfaff et al., 1996). However, several additional studies raise the possibility that in mouse and chick, Islet1 may also inhibit interneuron formation. For example, transplanting neural tubes from Islet1-deficient mice into chicks prevents the death of nascent motoneurons. These surviving cells express interneuron markers (Thaler et al., 2004), although it is unclear whether they project motoneuron-like axons out of the spinal cord or interneuron-like axons within the spinal cord. Similarly, mouse embryos with a targeted deletion of the Mnx family member Hb9 initially express Islet1 in nascent motoneurons, allowing these cells to develop as motoneurons and extend axons out of the spinal cord. However, Islet1 expression is very quickly extinguished ...
Neogenesis, the differentiation of islet beta cells from progenitor cells present in the pancreas, can continue into postnatal life, and has been reported to occur in several animal models. Recent studies have also demonstrated neogenesis of endocrine cells in vitro from ductal structures or from islet themselves derived from adult human and animals, suggest new possibilities for generating new beta cells in culture. Such strategies might provide models to study the regulation of islet differentiation as well as providing new sources of beta cells for transplantation, but the nature of endocrine progenitors identity and the signals that regulate neogenic activity need to be elucidated. The research focus in my laboratory are: (i) the molecular events controlling pre- and postnatal beta-cell development and maturation, and (ii) the characterization of optimal culture environments for inducing progenitors to differentiate into insulin-producing islet cells, maintaining islet architecture and ...
Regulated exocytosis, modelled by insulin secretion stimulated by glucose and other secretagogues from pancreatic islet beta cells is mediated by multiple signaling pathways. Rac1, a member of Rho GTPase, primarily regulates the formation of lamellipodial and ruffles by reorganization of cell membrane cortex filamentous actins. By expressing mutated forms of Rac1 in insulin-secreting INS-1 cells that altered the nature of insulin secretion and morphology, this study demonstrated that Rac1 is involved in glucose and forskolin stimulated insulin secretion, probably at the level of recruitment of secretory granules through actin cytoskeletal reorganization. Expression of syncollin, a secretory granule associated protein originally expressed in exocrine cells, in insulin-secreting INS-1 cells, indicated that complete, not truncated form syncollin, can be sorted into insulin secretory granules specifically and impair regulated insulin secretion in a Ca2+-independent way. This suggests that syncollin ...
Scientists have discovered that a surprisingly high percentage of people with type 1 diabetes (insulin-dependent) who have had the disease for 50 years or longer may still have residual functioning, insulin-producing islet cells and/or islet cell antibodies.
Typically, patients with type 1 diabetes require lifelong insulin therapy. In combination with a healthy lifestyle and nutrition, regenerative medicine and stem cell therapy may provide individuals with the ability to decrease and possibly eliminate their insulin use. Stem cell therapy may also have the potential to repair tissues and organs damaged as a result of diabetes mellitus.. Recent studies show that Mesenchymal Stem Cells (MSCs) may have the ability to improve and possibly even reverse the effects of diabetes mellitus. MSCs have the capacity to differentiate and migrate to the site of damage and secrete growth factors or cytokines. In type 1 diabetes, the insulin producing cells - beta cells within the pancreatic islets - are being destroyed by the immune system. According to recent publications, MSCs may help increase insulin secretion, raise the number of islet cells in the pancreas, enhance islet survival, and treat diabetic ulcers and limb ischemia.. MSCs efficiently differentiate ...
Among most species, pancreatic islets are generally characterised by an oval shape. Nevertheless, the distribution of cells within the endocrine portion of the pancreas is subject to variation. In most mammals, the pancreatic islet contains a core of beta cells, which is encircled by a mantle of non-beta cells. Yet, in humans and primates, cells are dispersed with greater complexity and deviate from the mammalian mantle-core arrangement to a composite of several mantle-core subunits. Due to such cellular organisation, pancreatic islets within humans and primates may be oval of clover-leaf shaped. Islets of Langerhans are highly vascularised structures, which contain capillaries that are lined by endothelial cells comprising of mitochondria, ergastoplams, a golgi complex and a nucleus. The peripheral extensions of the cytoplasm of such endothelial cells are typically thinner and lack such organelles however contain several fenestrae, or openings. While it is not confirmed whether these fenestrae ...
Among most species, pancreatic islets are generally characterised by an oval shape. Nevertheless, the distribution of cells within the endocrine portion of the pancreas is subject to variation. In most mammals, the pancreatic islet contains a core of beta cells, which is encircled by a mantle of non-beta cells. Yet, in humans and primates, cells are dispersed with greater complexity and deviate from the mammalian mantle-core arrangement to a composite of several mantle-core subunits. Due to such cellular organisation, pancreatic islets within humans and primates may be oval of clover-leaf shaped. Islets of Langerhans are highly vascularised structures, which contain capillaries that are lined by endothelial cells comprising of mitochondria, ergastoplams, a golgi complex and a nucleus. The peripheral extensions of the cytoplasm of such endothelial cells are typically thinner and lack such organelles however contain several fenestrae, or openings. While it is not confirmed whether these fenestrae ...
Bennet H, Balhuizen A, Medina A, Dekker Nitert M, Ottosson Laakso E, Essén S, Spégel P, Storm P, Krus U, Wierup N, Fex M Peptides 71 (-) 113-120 [2015-09-00; online 2015-07-25] Islet produced 5-hydroxy tryptamine (5-HT) is suggested to regulate islet hormone secretion in a paracrine and autocrine manner in rodents. Hitherto, no studies demonstrate a role for this amine in human islet function, nor is it known if 5-HT signaling is involved in the development of beta cell dysfunction in type 2 diabetes (T2D). To clarify this, we performed a complete transcriptional mapping of 5-HT receptors and processing enzymes in human islets and investigated differential expression of these genes in non-diabetic and T2D human islet donors. We show the expression of fourteen 5-HT receptors as well as processing enzymes involved in the biosynthesis of 5-HT at the mRNA level in human islets. Two 5-HT receptors (HTR1D and HTR2A) were over-expressed in T2D islet donors. Both receptors (5-HT1d and 5-HT2a) were ...
The main focus of my lab is to understand how islets of Langerhans, the endocrine component of the pancreas, are formed during organogenesis, how their function is regulated in the mature organism, and how changes in gene expression might allow islet regeneration. Islet cells, including glucagon-producing a- and insulin-producing ß-cells, regulate blood glucose homeostasis. The importance of the latter is highlighted by the fact that loss of ß-cells leads to type I diabetes mellitus. Conventional treatment of diabetic patients is based on insulin injections. Unfortunately, episodes of hypo- and hyperglycemia occur frequently and result in severe secondary complications, including coronary and microvascular diseases. Recent reports have shown that islet transplantation successfully restores glucose tolerance. However islets are in short supply, a dilemma that severely restricts the feasibility of large-scale therapy through islet transplantation. An alternative approach is the regeneration of ...
Addition of pyruvate to rat islets perifused in the presence of 5 mM-glucose elicited an immediate pronounced biphasic stimulation of insulin secretion. At lower concentrations of glucose (2.5 mM), only the initial, transient, phase of secretion was observed. Pyruvate inhibited 45Ca2+ efflux from islets at 2.5 mM-glucose and stimulated efflux at 5 mM-glucose. Pyruvate also decreased the rate of efflux of 86Rb+ from perifused islets. A marked stimulation of insulin secretion and 45Ca2+ efflux rate was observed in response to 3-fluoropyruvate and 3-bromopyruvate, compounds which inhibited oxidative metabolism of [14C]glucose and [14C]pyruvate in islets. The stimulatory effects of 3-fluoro- and 3-bromo-pyruvate were associated with enhanced 86Rb+ efflux. Withdrawal of pyruvate or halogenated analogues from the perfusate resulted in a secondary stimulation of insulin release, 45Ca2+ efflux and, to some extent, 86Rb+ efflux rates. Pyruvate, 3-fluoropyruvate and 3-bromopyruvate were all effective in ...
Looking for islet cell? Find out information about islet cell. see pancreas pancreas , glandular organ that secretes digestive enzymes and hormones. In humans, the pancreas is a yellowish organ about 7 in. Explanation of islet cell