Glucose‐stimulated insulin secretion (GSIS) is modulated by a number of factors, such as non‐glucose nutrients, hormones and neural inputs (Figure 1). Thus, the intracellular network for regulation of insulin secretion is complex and multifactorial Glucose Stimulated Insulin Secretion - MIN6 | The Ku Lab Glucose Stimulated Insulin Secretion - MIN6 1) 3-5 days prior to experiment, seed 20,000 MIN6 cells per 96 well plate (Corning CellBind). 2) The day of the experiment, prepare fresh KRBH with 0.1% RIA grade BSA Glucose-stimulated insulin secretion (GSIS) is facilitated by an increase in cytosolic NADPH (4, 9 - 12), as various redox shuttles affecting metabolism generate cytosolic NADPH upon glucose intake, at the expense of NADH in the mitochondrial matrix (4, 9 - 12) Glucose-stimulated insulin secretion is the hallmark of a differentiated beta cell, and the early loss of this feature is a prominent event in the pathogenesis of type 2 diabetes [ 1, 2 ]. A wealth of data has identified a number of proteins, organelles and cells that interact during this event Glucose-stimulated insulin secretion is coupled to the interaction of actin with the t-SNARE (target membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein) complex. Thurmond DC (1), Gonelle-Gispert C, Furukawa M, Halban PA, Pessin JE
GSIS, glucose-stimulated insulin secretion Transcription Factor 7-Like 2 Regulates β-Cell Survival and Function in Human Pancreatic Islets Luan Shu, Nadine S. Sauter, Fabienne T. Schulthess, Aleksey V. Matveyenko, José Oberholzer, Kathrin Maedler Diabetes Mar 2008, 57 (3) 645-653; DOI: 10.2337/db07-084 It is commonly believed that the K ATP-dependent model of glucose-stimulated secretion coupling is the primary means used by the β-cell to activate insulin secretion (7-10). In this model, glucose enters the β-cell, is phosphorylated by glucokinase to glucose-6-phosphate, and then enters the glycolytic and oxidative phosphorylation pathways. A core biochemical mechanism controlling glucose-stimulated insulin secretion (GSIS) involves metabolism of glucose through glycolysis and the tricarboxylic acid (TCA) cycle to yield ATP, which suppresses ATP-sensitive potassium (K ATP) channels, leading to activation of voltage-gated Ca 2+ channels and Ca 2+ influx to trigger release of insulin-containing secretory granules In both models, insulin secretion could be stimulated by provision of either exogenous H 2 O 2 or diethyl maleate, which raises intracellular H 2 O 2 levels. Provision of exogenous H 2 O 2 scavengers, including cell permeable catalase and N -acetyl- l -cysteine, inhibited glucose-stimulated H 2 O 2 accumulation and insulin secretion (GSIS) Insulin Secretion. Insulin secretion stimulated by glucose is a complex process of signal transduction in beta cells, comprised of proximal events which include glucose internalization through glucose transporters (GLUT) and its catabolism through glycolysis, Krebs cycle, and oxidative phosphorylation, leading to a rise in ATP/ADP ratio, and by distal events, which include the activation of.
dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct beta-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lowe Insulin secretion primarily depends on elevated concentrations of glucose, and is regulated by nutrients, hormones and some small molecules (Jitrapakdee et al. 2010). An impaired glucose-stimulated insulin secretion (GSIS) may lead to beta cell failure, diabetes and other metabolic diseases (Jensen et al. 2008) The lack of CD38 in mice and humans causes an impaired glucose-stimulated insulin secretion [15, 17, 31]. In this context, TRPM5 could bring together metabolic effects and the triggering of insulin secretion Chronic palmitate exposure impairs glucose-stimulated insulin secretion and other aspects of β-cell function, but the underlying mechanisms are not known. Using various live-cell fluorescence imaging approaches, we show here that long-term palmitate treatment influences cAMP signaling in pancreatic β-cells
and glucose-stimulated insulin secretion Guo-Fang Zhang, 1,2,4 Mette V.Jensen, 1,4 Sarah M. Gray, 1 Kimberley El, 1 You Wang, 1 Danhong Lu, 1 Thomas C. Becker, 1,2 Jonathan E. Campbell, 1 ,2 3 and Christopher B. Newgard 5 In physiologic concentrations gastrin potentiates the glucose-stimulated insulin secretion and is without effect on basal insulin secretion. A small release of gastrin during oral glucose ingestion may to a limited extent contribute to the nonglycemic insulin secretion Effect of secretin on basal- and glucose-stimulated insulin secretion in man. Fahrenkrug J, Schaffalitzky de Muckadell OB, Kühl C. Plasma immunoreactive secretin and insulin concentrations were measured in fasting normal humans after intraduodenal infusions of hydrochloric acid, isotonic or hypertonic glucose To assess glucose-stimulated K ATP-independent insulin secretion, cells were treated with diazoxide and then depolarized with 30 mM KCl in the presence of 3 or 15 mM glucose (Figure 5A). Basal and stimulated insulin secretion were enhanced in the ΔSCS-ATP cells despite pharmacological elimination of the K ATP channels Actin Depolymerization by Latrunculin B Potentiates Glucose-Stimulated Insulin Secretion from MIN6 β-Cells, without Affecting Cellular Insulin Content MIN6 β-cells were incubated in glucose-free MKRBB in the presence of 10 μ m latrunculin B (LAT) or DMSO vehicle control (VEH) for 2 h followed by stimulation with 20 m m glucose over a 10-min period. A, Insulin secreted into the media over.
Filamentous actin (F-actin) cytoskeletal remodeling is critical for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells, and its dysregulation causes type 2 diabetes. The adaptor protein APPL1 promotes first-phase GSIS by up-regulating soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein expression The Glucose-Stimulated insulin Secretion (GSIS) test in vivo is a variant of the glucose tolerance test during which blood is sampled at key time points, in order to measure plasma insulin levels in the basal (fasted) state and after induction of hyperglycemia by a glucose bolus administered either intraperitoneally or orally.. During an intraperitoneal GSIS, the hyperinsulinemic profile is. Urocortin 3 (Ucn 3), a member of the corticotropin-releasing factor (CRF) family of peptides, is strongly expressed in mammalian pancreatic β cells and has been shown to stimulate insulin secretion. Here we report the investigation of the hypothesis that endogenous Ucn 3 regulates insulin secretion, particularly in the presence of nutrient excess Insulin sensitivity did not exhibit significant changes from the glucose only condition. We conclude that the acute combined administration of the strongly insulinotropic GLP-1 and glucagon, both in vivo and in vitro, did not induce any additive or synergistic action on glucose-stimulated insulin secretion
The Glucose-Stimulated insulin Secretion (GSIS) test in vivo is a variant of the glucose tolerance test during which blood is sampled at key time points, in order to measure plasma insulin levels in the basal (fasted) state and after induction of hyperglycemia by a glucose bolus administered either intraperitoneally or orally Static glucose stimulated insulin secretion (GSIS) protocol for mouse islets Home > Glucose Stimulated Insulin Secretion - MIN6 Glucose Stimulated Insulin Secretion - MIN6 1) 3-5 days prior to experiment, seed 20,000 MIN6 cells per 96 well plate (Corning CellBind). 2) The day of the experiment, prepare fresh KRBH with 0.1% RIA grade BSA. 3) Flick media from plate. Blot briefly on paper towel
Glucose-stimulated insulin secretion (GSIS) and its correlation to lipolysis were investigated in INS-1 cells. In cells cultured at 11.1 mM glucose, acute stimulation with 16.7 mM glucose resulted in a robust 4-fold increase in insulin secretion compared to basal secretion at 3.3 mM glucose (P < 0.01) (Fig. 1A). The acute response to glucose stimulation was less pronounced in cells cultured at. Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic β-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110γ isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets G protein-coupled receptor 40 (GPR40) contributes to medium- or long-chain fatty acid-induced amplification of glucose-stimulated insulin secretion (GSIS) and GPR40 agonists are promising.. Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells requires an increase in intracellular free Ca 2+ concentration ([Ca 2+ ]). Glucose uptake into β-cells promotes Ca 2+ influx and reactive oxygen species (ROS) generation Glucose-stimulated insulin secretion is ensured by multiple molecular, cellular and tissue events. In this issue of Diabetologia , Low et al (DOI: 10.1007/s00125-013-3019-5 ) have taken an important new step towards understanding the hierarchical organisation of these events, by monitoring in vitro the individual exocytosis of multiple beta cells within intact mouse islets. The authors show.
Ex vivo, islet Mt1 and Mt2 mRNA and MT1 and MT2 protein levels were downregulated after culture with glucose at 10-30 mmol/l vs 2-5 mmol/l, in association with increased insulin secretion. In human islets, mRNA levels of MT1E, MT1X and MT2A were downregulated by stimulation with physiological and supraphysiological levels of glucose Impaired glucose-stimulated insulin secretion (GSIS) is an established marker of β-cell dysfunction in prediabetes, including impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), which affects >30% adult population (4, 5) The triggering pathway has been considered to be the main pathway during glucose-stimulated insulin secretion. Glibenclamide, a K ATP channel blocker widely used in the treatment of type 2.. Glucose-stimulated insulin secretion (GSIS) is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM). Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion
To assess the effects of coxiol on biphasic glucose-stimulated insulin secretion, we perifused, isolated mouse islets with glucose-containing buffer in the presence or absence of coixol. Coixol significantly stimulated insulin secretion in high glucose (16.7 mM), but not at low glucose (2.8 mM) conditions (Fig. 1 C, P < 0.05) The second phase of glucose‐stimulated insulin secretion is due mainly to the K ATP channel‐independent pathways acting in synergy with the K ATP channel‐dependent pathway. The rate‐limiting step here is the conversion of readily releasable granules to the state of immediate releasability, following which, in an activated cell they will. CONCLUSION: TNFα suppresses both basal and glucose-stimulated insulin transcription and secretion in HIT-T15 cells, an effect that is enhanced significantly by high glucose. Leptin also.. Glucose-stimulated insulin secretion occurred progressively from 5 mmol/l glucose, reached the maximal level approximately seven-fold above the basal level at 25 mmol/l, and remained at this level up to 50 mmol/l. Glucose transport was very rapid with the half-maximal uptake of 3-O-methyl- d -glucose being reached within 15 s at 22 °C Compared with amlodipine, fimasartan increased late‐phase glucose‐stimulated insulin secretion in patients with type 2 diabetes and hypertension. This finding suggests that ARBs would be more beneficial in such patients compared with other classes of anti‐hypertensives
Glucose stimulated insulin secretion time courses were studied and as expected, LP MIN6 cells secreted increasing amounts of insulin over time . Interestingly, HP cells eventually responded to glucose at 60 minutes, however this was still significantly less than LP MIN6 cells (p<0.05) In beta cells, insulin release is stimulated primarily by glucose present in the blood. As circulating glucose levels rise such as after ingesting a meal, insulin is secreted in a dose-dependent fashion. This system of release is commonly referred to as glucose-stimulated insulin secretion (GSIS). There are four key pieces to the Consensus Model of GSIS: GLUT2 dependent glucose uptake. NADPH facilitates glucose-stimulated insulin secretion (GSIS) in pancreatic islet (PI) β-cells by an as yet unknown mechanism. We found NADPH oxidase, isoform-4 (NOX4), to be the major producer.
CNC-bZIP Protein Nrf1-Dependent Regulation of Glucose-Stimulated Insulin Secretion. Hongzhi Zheng, Jingqi Fu, Peng Xue, Rui Zhao, Jian Dong, Dianxin Liu, Masayuki Yamamoto, Qingchun Tong, Weiping Teng, Weidong Qu, Qiang Zhang, Melvin E. Andersen, and ; Jingbo P , and its impairment is a key element of β cell failure in type II diabetes
Glucose‐induced insulin secretion is determined by signals generated in the mitochondria. The elevation of ATP is necessary for the membrane‐dependent increase in cytosolic Ca 2+, the main trigger of insulin exocytosis Glucose‐stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet β cells, and extracellular‐regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen‐activated protein kinase family that regulates this process Besides insulin‐mediated transport of glucose into the cells, an important role is also played by the non‐insulin‐mediated transport which is called glucose effectiveness (acronym SG). This process a.. HNGF6A increases glucose‐stimulated insulin secretion (GSIS) in vivo. To determine the effects of HNGF6A on GSIS in vivo, we performed the gold standard hyperglycemic clamps in 3‐mo‐old male Sprague‐Dawley rats. Control and HNGF6A‐treated groups were matched in terms of age, gender, body weight, and basal glucose and insulin levels
Aims: Glucose-stimulated insulin secretion (GSIS) in pancreatic β cells was expected to enhance mitochondrial superoxide formation. Hence, we elucidated relevant redox equilibria First Phase of Glucose-Stimulated Insulin Secretion from Pancreas Consists of Three Different Pathways Including ATP-Sensitive Potassium Channel The first phase of glucose-sti The first phase of glucose-stimulated insulin secretion (GSIS) from the pancreas is well known to be mainly through ATP-sensitive potassium (K[sub]ATP[/sub]) channel/voltage-dependent calcium channel (VDCC) pathway
We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS). In conditioned media from human myotubes incubated with/without insulin (100 nmol/L) for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively Glucose‐dependent insulinotropic peptide (GIP) exerts multiple biological effects via the G‐protein‐coupled receptor GIPR, including glucose‐stimulated insulin production and secretion, cell prolifer.. Glucose-stimulated insulin secretion was lower in islets from Gα q /Gα 11 knockout mice than those from WT mice even at physiological pH , supporting the involvement of G q/11 protein activation through unidentified GPCR in glucose-stimulated insulin secretion under the condition. The present study suggests that one of the unidentified GPCR. SIRT2 promotes glucose-stimulated insulin secretion in rat islets. (A) Islets isolated from . SIRT2-WT and SIRT2-KO rats were stimulated with 3.3, 8.3 or 16.7 mM glucose f The loss of glucose-stimulated insulin secretion from these β cells marks the onset of T2D. In a study published online Sept. 24 in the journal Cell Reports , the research team found a significant increase in the purine/nucleotide metabolic pathway intermediate adenylosuccinate (S-AMP) in islets stimulated with glucose
Impaired insulin secretion by pancreatic β‐cells is an important hallmark of type 2 diabetes . Thus, understanding the mechanisms involved in glucose‐stimulated insulin secretion (GSIS) is of major significance. ATP is an important downstream signal of nutrient metabolism, which stimulates insulin release by pancreatic β‐cells Glucose-stimulated insulin secretion to a decrease in insulin secretion. This defect seems to be as assessed by an 18-mmol/l clamp is also decreased in old specific for glucose and not to stimuli such as FFAs. age. Because insulin clearance may be decreased in aging With increasing age, changes in anthropometric charac- (27,28), the lower. During glucose-stimulated insulin secretion, while dextrose was administered at a rate of 8 and 10 mg/kg per min for 40 min each step on the day of sham clamp, glucose requirements to maintain similar glycemia were markedly higher following preexposure to insulin (an additional 12 ± 2 and 20 ± 3 mg·kg −1 ·min −1 , first and second step.
, including cell proliferation, apoptosis, oxidative stress, inflammatory responses, and glucose-stimulated insulin secretion, and these regulatory functions are probably mediated via AT1R [ Elevation of glucose levels in the blood primarily stimuli insulin secretion. Moreover, increased blood levels of amino acids and fatty acids also got a response by insulin secretion. Ingested food raises blood glucose levels rapidly. This elevated glucose in the blood then enters into beta cells Glucose‐stimulated biphasic insulin secretion involves at least two signaling pathways, the K ATP channel‐dependent and K ATP channel‐independent pathways, respectively Perturbation of Pim3 function resulted in enhanced glucose-stimulated insulin secretion, both in MIN6 cells and in isolated islets from Pim3-/- mice, where the augmentation was speciically seen in the second phase of secretion. Consequently, Pim3-/- mice displayed an increased glucose tolerance in vivo
Lixisenatide increased the 16.7 mM glucose-stimulated insulin secretion, but not by 5.6 mM glucose, in the islets of healthy rats, without changing the insulin intracellular content After starvation, medium was exchanged for KRB (300 ul) containing 20 mM glucose to measure glucose-stimulated insulin secretion during 1 hr incubation. The kit used is from Millipore (EZRMI-13K)... Mitochondrial oxidative metabolism is central to glucose-stimulated insulin secretion (GSIS). Whether Ca 2+ uptake into pancreatic beta cell mitochondria potentiates or antagonises this process is still a matter of debate
For over 30 years, one particular model of glucose stimulus/ Conversely, robust glucose-stimulated insulin secretion (GSIS) secretion coupling has gained wide acceptance. In this con- in postprandial periods prevents hyperglycemia. Importantly, struct, the rise in blood glucose induces an increase in ␤-cell impairment of insulin-secretory. This new system was tested by measuring glucose-stimulated insulin secretion from single and groups of murine and human islets. Distinct islet entrainment of groups of murine islets by pulses of CCh was also observed, providing further evidence for the hypothesis that pulsatile output from the ganglia can synchronize islet behavior Glucose-stimulated insulin secretion (GSIS) is central to normal control of metabolic fuel homeostasis, and its impairment is a key element of beta-cell failure in type 2 diabetes. Glucose exerts its effects on insulin secretion via its metabolism in beta-cells to generate stimulus/secretion coupling factors, including a rise in the ATP/ADP. In this study, INS‐1 cells, a cell line which exhibit glucose‐stimulated insulin secretion, were embedded in fibrin and cultured under perfusion bioreactor conditions for 48 h and then exposed to either a high‐, or low‐glucose concentration for 24 h. These cultures were compared to non‐bioreacted controls
Phosphorylation plays pivotal roles in islet function, especially in islet glucose-stimulated insulin secretion. A systematic view on how phosphorylation networks were coordinately regulated in this process remains lacking, partially due to the limited amount of islets from an individual for a phosphoproteomic analysis Glucose-stimulated insulin secretion (GSIS) in the pancreatic b cell is mainly regulated by the glucose-stimulated triggering and amplifying pathways by a varietyoffactors(5).Thesequenceofeventsthatoccurs as part of the triggering pathway are well establishe
Glucose-Stimulated Insulin Secretion Mean plasma glucose and insulin concentrations after the oral glucose tolerance test in 12 healthy volunteers are shown in Table 2 Differences in glucose-stimulated insulin secretion (GSIS) are noticeable not only in diabetic individuals but also in model pancreatic β cells, e.g., βTC3 and MIN6 β cell lines with impaired and normal insulin secretion, respectively A fatty acid- dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion. R L Dobbins, M W Chester, B E Stevenson, M B Daniels, D T Stein, and J D McGarry Department of Internal Medicine, Center for Diabetes Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235, USA..
Imeglimin increases glucose-stimulated insulin secretion in vivo and in vitro in chow-fed rats. A and B: plasma glucose and glucose area under the curve (AUC) during a glucose tolerance test. C and D: plasma insulin and insulin AUC during a glucose tolerance test. Data are means ± SE of n = 6/group islets at potentiating glucose-stimulated insulin secretion. We compared Compound A-induced GPR40 activity to that induced by both fasiglifam and AM-1638, another allosteric full agonist previously reported to be highly efficacious in preclinical models, at a panel of G proteins. Compound A was a full agonist at both the GaqandGai2 pathways. -Cell-speciﬁc pyruvate dehydrogenase deﬁciency impairs glucose-stimulated insulin secretion Malathi Srinivasan,1 Cheol S. Choi,2,3 Pushpankur Ghoshal,1 Lioudmila Pliss,1 Jignesh D. Pandya,1 David Hill,4 Gary Cline,2 and Mulchand S. Patel1 1Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, The State University o Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting
Glucose-stimulated insulin secretion (GSIS) is mediated in part by glucose metabolism-driven increases in ATP/ADP ratio, but by-products of mitochondrial glucose metabolism also play an important role. Here we investigate the role of the mitochondrial citrate/isocitrate carrier (CIC) in regulation of GSIS. Inhibition of CIC activity in INS-1-derived 832/13 cells or primary rat islets by the. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β -cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods In both clonal and human islets, metformin has been shown to inhibit glucose-stimulated insulin secretion (GSIS) by increasing AMP-activated protein kinase activity . However, typical circulating levels [ 16 - 19 ] of metformin in the body are 1-2% of the concentrations used in these studies or lower
Amongst other hypotheses, it has been suggested that Mg 2+ deficiency affects insulin secretion. The aim of this study was, therefore, to investigate the acute effects of extracellular Mg 2+ on glucose-stimulated insulin secretion in primary mouse islets of Langerhans and the rat insulinoma INS-1 cell line Myo1b depletion by siRNA in 832/13 cells reduced intracellular proinsulin and insulin content and glucose-stimulated insulin secretion (GSIS), and led to the accumulation of (pro)insulin SGs at the TGN. Using an in situ fluorescent pulse-chase strategy to track nascent proinsulin. PGC-1 alpha Genotype Affects PGC-1 alpha mRNA Expression and Glucose-Stimulated Insulin Secretion in Isolated Human Pancreatic Islets Recent studies have implicated Recent studies have implicated PGC-1-alpha in defects of oxidative phosphorylation in muscle of diabetic and pre-diabetic individuals It has been well established that excessive levels of glucose and palmitate lower glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells. This β-cell 'glucolipotoxicity' is possibly mediated by mitochondrial dysfunction, but involvement of bioenergetic failure in the pathological mechanism is the subject of ongoing debate
Stimulus/Secretion Coupling Factors in Glucose-Stimulated Insulin Secretion Insights Gained From a Multidisciplinary Approach Christopher B. Newgard,1 Danhong Lu,1 Mette Valentin Jensen,1 Jonathan Schissler,1 Anne Boucher,1 Shawn Burgess,2 and A. Dean Sherry2 There is a growing appreciation for the complexity of sive, potentiating, and inhibitory agents that modulate the the pathways involved. Notably, chronic aspartame exposure did not have the same effect, which indicates this increase in glucose-stimulated insulin secretion (GSIS) was unique to fructose and not merely due to binding of the T1R2 receptor (5) The relevance of Kir-GEM in insulin secretion was made evident by its attenuation of glucose-stimulated Ca2+ increases and C-peptide secretion in an insulin-secreting cell line. The potential therapeutic role of Kir-GEM lies in the inhibitory effects on VDCC activity that may serve to protect beta cells from overstimulation and subsequent. Therefore, GH receptor plays critical roles in glucose-stimulated insulin secretion and β cell compensation in response to a high-fat diet. Introduction β Cell mass changes according to insulin demand, and loss of β cell hyperplasia in the face of insulin resistance is fundamental to the pathogenesis of type 2 diabetes ( 1 )
and immunofluorescence techniques were used to examine the expression of NA receptor PUMA-G, a member of the G protein-coupled receptor (G-PCR) family, in murine islet β cells. Calcium transient was measured using confocal microscopy, whereas the intracellular cyclic adenosine monophosphate and glucose-stimulated insulin secretion (GSIS) from isolated islets were determined by the enzyme. Finally, a significant loss of glucose-stimulated insulin secretion was demonstrated in INS1 cells and mouse pancreatic islets. In conclusion, Drp1 expression is important in pancreatic beta cells to maintain the regulation of insulin secretion. -- Highlights: •Down-regulation of Drp1 in INS1 cells reduces mitochondrial fusion protein expression integrative physiology trpm5 glucose-stimulated insulin secretion trpm5 mouse electrical activity vivo glucose tolerance test cellular ion concentration major role coordinated alteration trpm5 mouse maintain cellular membrane cation channel additional ion channel presented result intracellular ca2 release enable insulin vesicle fusion. Chronic fructose exposure potentiates glucose-stimulated insulin secretion (GSIS) in INS-1E β-cells through extracellular ATP signaling mediated by pannexin1 (Panx1) channel and P2Y1 purinergic receptors. Cells were cultured for 4 days in complete medium (CM) and CM supplemented with 5.5 mM fructose (CM + F) before a 3-h starving period and. These studies found higher glucose-stimulated insulin secretion (GSIS) following a 4h isoglycemic-hyperinsulinemic clamp when compared with a 4h saline infusion [7, 8]. This finding was in line with an in vitro study reporting higher insulin secretion after insulin stimulation 
Glucose‐stimulated insulin secretion was also impaired in islets isolated from mice expressing RARdn. Among genes that are atRA responsive, Glut2 and Gck mRNA levels were decreased in isolated islets from RARdn‐expressing mice. Histologic analyses of RARdn‐expressing pancreata revealed a decrease in β‐cell mass and insulin per β. Insulin potentiates glucose-stimulated insulin secretion in insulin-resistant subjects to a lesser degree than in normal subjects. This is consistent with an effect of insulin to regulate β-cell function in humans in vivo with therapeutic implications Mitochondrial metabolism is pivotal for glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. However, little is known about the molecular machinery that controls the homeostasis of intermediary metabolites in mitochondria On day three, testing of glucose-stimulated insulin secretion (GSIS) will occur as outlined below. Subjects will be provided with an isocaloric diet consisting of 50% calories derived from carbohydrates, 30% fat and 20% protein during the 48 hour infusions and will fast from midnight for the testing of pancreatic beta cell function on day three FIGURE 9 The MPC inhibitor UK5099, AdsiMPC1, and AdsiMPC2 inhibit glucose-stimulated insulin secretion from rat and human islets. A, glucose-stimulated insulin secretion in response to UK5099 from rat islets (n = 10). B, 30 m m KCl- and 100 μ m diazoxide-stimulated insulin secretion in the presence or absence of glucose from rat islets (n = 6) One potential factor that is a downstream effector of PKB that has been reported to be involved in insulindependent GLUT4 cell‐surface translocation in muscle and adipocytes and in glucose‐stimulated insulin secretion in the pancreatic β‐cell is the Rab GTPase‐activating protein AS160 . Interestingly, siRNA‐mediated knockdown of PI3K.