Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8537016 | Pharmacology & Therapeutics | 2017 | 39 Pages |
Abstract
Pancreatic islet β cells secrete insulin in response to nutrient secretagogues, like glucose, dependent on calcium influx and nutrient metabolism. One of the most intriguing qualities of β cells is their ability to use metabolism to amplify the amount of secreted insulin independent of further alterations in intracellular calcium. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive. Recent studies utilizing metabolomics, computational modeling, and animal models have progressed our understanding of the metabolic amplifying pathway of insulin secretion from the β cell. New approaches will be discussed which offer in-roads to a more complete model of β cell function. The development of β cell therapeutics may be aided by such a model, facilitating the targeting of aspects of the metabolic amplifying pathway which are unique to the β cell.
Keywords
Kir6.2HMG-CoAGIPKATP5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosideGLUT2Malic enzyme 1KCNJ11PKDZMPRhoGDI5-aminoimidazole-4-carboxamide ribonucleotideABCC8GSISSENP1ME2SENPAdenylosuccinateME1me3Hydroxymethylglutaryl-CoADPP-IVAICARSUMOG6PDGDHMAGmonoacylglycerolGPCRPLCGLP-1GLUT1PKCNAD(P)HSUR1SCHADGlucose-stimulated insulin secretiondipeptidyl peptidase 4Cell signalingphospholipase CMetabolomicsnicotinamide adenine dinucleotide (phosphate)protein kinase DProtein kinase Cglucagon-like peptide 1Gastric inhibitory peptideATP-sensitive potassium channelsmall ubiquitin-like modifierglutamate dehydrogenaseglucose transporter 1glucose transporter 2glucose-6-phosphate dehydrogenaseGlucose Sensingsulfonylurea receptor 1G protein-coupled receptor
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Authors
Michael A. Kalwat, Melanie H. Cobb,