imprint. Finally, INS-1E incubation with gliadin digest potentiated palmitate-induced insulin secretion by 13% compared to controls. KATP Channels. Incretins, the gut hormones such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP1), which are secreted from enteroendocrine K-cells and L-cells, respectively, following meal ingestion stimulate insulin secretion in a glucose-concentration-dependent manner to prevent postprandial … The main findings of this study are that α-synuclein is a cytoplasmic ligand of the insulin-secretory granule, interacts with the K ATP channel, and has an inhibitory action on insulin secretion. Ashcroft. series title. They have also been found in pancreas where they control insulin secretion, but are in fact widely distributed in plasma membranes. K-ATP channels and insulin secretion disorders. SarcK ATP are composed of eight protein subunits ( octamer ). Search text. Crossref Medline Google Scholar; 71. The causal mechanisms remain unknown. This review summarizes advances in our understanding of the structure and function of the ATP-sensitive potassium (KATP) channel of the pancreatic β-cell that have been made over the last 5 years. September 2002; AJP Endocrinology and Metabolism 283(2): E207-16; DOI: 10.1152/ajpendo.00047.2002. The KATP channels play an integral role in glucose-stimulated insulin secretion by serving as the transducer of a glucose-generated metabolic signal (ie, ATP) to cell electrical activity (membrane depolarization). Inhibition of the mitochondrial KATP channel by long-chain acyl-CoA esters and activation by guanine nucleotides. Crossref. Free full text . In diabetes, glucagon secretion is not suppressed at high glucose, exacerbating the consequences of insufficient insulin secretion, and is inadequate at low glucose, potentially leading to fatal hypoglycemia. Glucose-induced insulin secretion from pancreatic β-cells critically depends on the activity of ATP-sensitive K + channels (K ATP channel). Keywords: KATP channel; SGLT1; GIP secretion. 1), in contrast to the effect of sulfonylureas and KCl where the increase of insulin preceded the decrease of glucagon. In pancreatic β-cells, KATP channels play a key role in glucose-stimulated insulin secretion, and gain or loss of channel function results in neonatal diabetes or congenital hyperinsulinism, respectively. Thus, Ca 2+ facilitates exocytosis and KATP channels regulate glucose-stimulated insulin secretion by controlling Ca*+ channel P. K(ATP) channels and islet hormone secretion: new insights and controversies. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. However, many drugs block KATP as “off targets” leading to hyperinsulinaemia and hy By immunostaining, α-synuclein was localized with the insulin granule luminal cargo markers C-peptide and insulin and with insulin-secretory granule membrane markers Kir6.2 and SUR1. author. 2013; 18 (6): 871 – 882. This article reviews the cloning, molecular biology, and structure of KATP channels, with particular focus on the SUR1/KIR6.2 neuroendocrine channels that are important for the regulation of insulin secretion. Henry Stewart talks. The glucose-lowering effect of insulin, as assessed by an insulin tolerance test, is increased significantly in Kir6.2−/−, which could protect Kir6.2−/− from developing hyperglycemia. Ion channels : mediators of ion currents across cell membranes. The KATP channels in pancreatic beta-cells are thought to be critical in the regulation of glucose-induced and sulfonylurea-induced insulin secretion. The glucose-lowering effect of insulin, as assessed by an insulin tolerance test, is increased significantly in Kir6.22y2, which could protect Kir6.22y2 from developing hyperglycemia. Pathway Involved in Potentiation of Insulin Secretion by Efaroxan Sue L.F. Chan, Mirna Mourtada, and Noel G. Morgan Efaroxan, like several other imidazoline reagents, elic- its a glucose-dependent increase in insulin secretion from pancreatic -cells. Ion channels . PubMed 8. The mitochondrial KATP channel as a receptor for potassium channel openers. Abstract. P1 islets had lower insulin release in response to tolbutamide, an inhibitor of β-cell K ATP channels, compared to P14 islets, suggesting that decreased K ATP channel expression and/or function could be responsible for the lower glucose threshold for insulin secretion. In this study, bupropion was shown to inhibit KATP channel activity in pancreatic β-cell membranes and induce insulin secretion in relatively high concentration. Ashcroft, Frances M. title. stimulates insulin exocytosis in concert with other second messengers, including cyclic nucleotides, the hydrolytic products of phospholipases (A2, C, and D), and adenine and guanine nucleotides. Aims KATP ion channels play a key role in glucose‐stimulated insulin secretion. In healthy subjects, the rate of insulin secretion, facilitated by the secretion of gut-derived incretins (130), closely mirrors the glucose concentration. This study shows, for the first time, that bupropion has a direct electrophysiological action on pancreatic β-cells and can cause insulin secretion and also highlights the risk of using bupropion during pregnancy. The last five or six years have seen rapid advance in understanding the molecular basis of K ATP channel activity and the molecular genetics of HI. The KATP channel is a complex of 8 polypeptides comprising four copies of the protein encoded by the ABCC8 (ATP-binding cassette, sub-family C, member 8) gene and four copies of the protein encoded by the KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) gene. J Biol Chem. Nutrient oxidation in β-cells leads to a rise in [ATP]-to-[ADP] ratios, which in turn leads to reduced KATP channel activity, depolarization, voltage-dependent Ca 2+ channel activation, Ca 2+ entry, and exocytosis. H 2 S production and insulin secretion in INS‐1E cells A, glucose‐mediated H 2 S production in INS‐1E cells. Additionally, gliadin digest was shown to decrease current through KATP-channels. Persistent hyperinsulinemic hypoglycemia of infancy (HI) is a genetic disorder characterized by dysregulated insulin secretion and, although rare, causes severe mental retardation and epilepsy if left untreated. Four of these are members of the inward-rectifier potassium ion channel family K ir 6.x (either K ir 6.1 or K ir 6.2 ), while the other four are sulfonylurea receptors ( SUR1 , SUR2A , and SUR2B ). *P < 0.05 versus other groups.n= 4 for each group. Introduction. Given that closure of the same channels in β-cells leads to stimulation of insulin secretion, the inhibition of glucagon secretion seen in K ATP-channel knockout mice might seem paradoxical. Cell Metab. Biomedical & life sciences collection. FM, Rorsman. insulin secretion, Kir6.22y2 show only mild impairment in glucose tolerance. The critical involvement of ATP-sensitive potassium (KATP) channels in insulin secretion is confirmed both by the demonstration that mutations that reduce KATP channel activity underlie many if not most cases of persistent hyperinsulinemia, and by the ability of sulfonylureas, which inhibit KATP channels, to enhance insulin secretion in type II diabetics. Google Scholar. [4] In addition to impaired insulin secretion (57 ... Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes. It then considers the molecular mechanism by … Alternatively, use our A–Z index Endogenous production of H 2 S was significantly decreased by high glucose concentration in the incubation medium. KATP channels and insulin secretion [electronic resource] / Frances Mary Ashcroft. 1996; 271:32084–32088. series title. Search type Research Explorer Website Staff directory. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. ion channel in the regula-tion of insulin secretion is well characterized.1 An extensive range of compounds is known to block the KATP channel; canonically these are sulphonylureas, such as tolbutamide,2 gliclazide,3 glip-izide4 and glibenclamide2,4; and glitinides, such as meglitinide2 and repaglinide. Despite the defect in glucose-induced insulin secretion, Kir6.2−/− show only mild impairment in glucose tolerance. Indeed, this process is energetically equal to glucose-stimulated insulin secretion (GSIS). Objective Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. This article reviews the cloning, molecular biology, and structure of KATP channels, with particular focus on the SUR1/KIR6.2 neuroendocrine channels that are important for the regulation of insulin secretion. Nutrient oxidation in β-cells leads to a rise in [ATP]-to-[ADP] ratios, which in turn leads to reduced KATP channel activity, depolarization, voltage-dependent Ca 2+ channel activation, Ca 2+ entry, and exocytosis. Here we consider the role of K ATP -channels in the α-cell focusing on the effects exerted by closure of these channels on α-cell electrical activity and glucagon secretion and the possible … J Biol Chem. Source; PubMed; Authors: Hanna Huopio. Nat Rev Endocrinol. Proc Natl Acad Sci U S A. PPG (5 m m) treatment of INS‐1E cells significantly reduced endogenous H 2 S production. Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Raising the glucose concentration from very low to maximally effective on insulin secretion decreased glucagon and increased insulin secretion during the same collection period (see Fig. Garlid KD, Paucek P, Yarov-Yarovoy V, Sun X, Schindler PA. Potassium channels. Activation of KATP channels by H2Sinrat insulin-secreting cells and the underlying mechanisms Wei Y ang1,Guangdong Yang1,Xuming Jia2, ... and insulin secretion in INS-1E cells were determined. Decreased KATP channel activity contributes to the low glucose threshold for insulin secretion in the early postnatal period Published in: bioRxiv, March 2021 DOI: 10.1101/2021.03.04.433947: Authors: Juxiang Yang, Batoul Hammoud, Changhong Li, Abigail Ridler, Daphne Yau, Junil Kim, Kyoung-Jae Won, Charles A Stanley, Toshinori Hoshi, Diana E Stanescu View on publisher site Alert me about … A specific gliadin 33-mer had a similar effect, both on current and insulin secretion. More Details. Search ADS. It discusses recent structural studies of the octameric KATP channel complex and studies of the regulation of KATP channel activity by nucleotides. Until recently, however, the molecular structure of the KATP channel was not known. Coronavirus: ... Our data indicate that the KATP channel in pancreatic beta cells is a key regulator of both glucose- and sulfonylurea-induced insulin secretion and suggest also that the KATP channel in skeletal muscle might be involved in insulin action.

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