...Mauricio Di Fulvio; Lydia Aguilar-Bryan It is accepted that insulin-secreting β-cells release insulin in response to glucose even in the absence of functional ATP-sensitive K + (K ATP )-channels, which play a central role in a ‘consensus model’ of secretion broadly accepted and widely reproduced...

... a pivotal part of this regulation as they are primarily responsible for controlling cellular and circulating amino acid concentrations. The availability of amino acids regulated by transporters can amplify insulin secretion and modulate insulin signalling in various tissues. In addition, insulin itself can...

...Charles Affourtit; Ben Alberts; Jonathan Barlow; Jane E. Carré; Anthony G. Wynne The canonical model of glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells predicts a glucose-induced rise in the cytosolic ATP/ADP ratio. Such bioenergetic sensitivity to metabolic fuel is unusual...

...Jonathan M. Locke; Lorna W. Harries Recent studies in mouse, involving the β-cell-specific deletion of Dicer1, have highlighted the crucial role of miRNAs (microRNAs) in regulating insulin secretion and consequently Type 2 diabetes. Identifying the individual miRNAs involved in human islet...

...Angela McDonald; Sarah Fogarty; Isabelle Leclerc; Elaine V. Hill; D. Grahame Hardie; Guy A. Rutter Glucose-stimulated insulin secretion from pancreatic β-cells requires the kinesin-1/Kif5B-mediated transport of insulin granules along microtubules. 5′-AMPK (5′-AMP-activated protein kinase...

...Mary C. Sugden; Mark J. Holness In healthy individuals, a hyperbolic relationship exists between whole-body insulin-sensitivity and insulin secretion. Thus, for any difference in insulin-sensitivity, a reciprocal proportionate change occurs in insulin secretion. Such a feedback loop is evident...

... (email t.biden@garvan.org.au ). 21 4 2008 © The Authors Journal compilation © 2008 Biochemical Society 2008 glucose-stimulated insulin secretion insulin secretion lipotoxicity pancreatic β-cell protein kinase C (PKC) Type 2 diabetes The PKC (protein kinase C) family...

.... In the present review, we focus on exogenous and endogenous effects of NEFAs, including the polyunsaturated fatty acid, arachidonic acid (or its metabolites generated from cyclo-oxygenase activity), on β-cell metabolism, and have explored the outcomes with respect to β-cell insulin secretion. 1 To whom...

... have been associated with reduced glucose and GLP-1 (glucagon-like peptide 1)-stimulated insulin secretion. Recent evidence has suggested that inheritance of the at-risk T allele at SNP rs7903146 may increase the expression of TCF7L2 in adult human islets. However, the cellular mechanisms by which...

...P. Newsholme; K. Bender; A. Kiely; L. Brennan In addition to the primary stimulus of glucose, specific amino acids may acutely and chronically regulate insulin secretion from pancreatic β-cells in vivo and in vitro . Mitochondrial metabolism is crucial for the coupling of glucose, alanine...

...C.B. Chan; N. Kashemsant UCPs (uncoupling proteins) can regulate cellular ATP production by uncoupling oxidative phosphorylation. UCP2 is expressed in islet β-cells and its induction reduces glucose-stimulated insulin secretion. Under physiological conditions, superoxide, formed as a by-product...

... to this signal transduction mechanism, mitochondria integrate and generate metabolic signals, thereby coupling glucose recognition with insulin secretion. In response to a glucose rise, nucleotides and metabolites are generated by mitochondria and participate, together with cytosolic Ca 2+ , in the stimulation...

...-cell level. Changes in these parameters, including the premature termination of single exocytotic events, are demonstrated as a possible contributor to the overall deficiency in insulin secretion observed in Type 2 diabetes [ 19 ]. Are there changes in the nature of release events...

...-cells is normal, glucose fails to close pancreatic β-cell K ATP channels or to elevate intracellular calcium and stimulate insulin secretion. This suggests a defect in glucose metabolism. Genetic mapping identified a loss-of-function mutation in the gene encoding Nnt (nicotinamide nucleotide...

...G.A. Rutter; A. Varadi; T. Tsuboi; L. Parton; M. Ravier Defective insulin secretion from pancreatic islet β-cells is a sine qua non of Type II (non-insulin-dependent) diabetes. Digital imaging analysis of the nanomechanics of individual exocytotic events, achieved using total internal reflection...

... glucose and fatty acids interact. These include stimulation of hepatic glucose output by fatty acids, potentiation of glucose-stimulated insulin secretion by fatty acids, and the cellular mechanism whereby high glucose and insulin concentrations inhibit fatty acid oxidation via malonyl-CoA regulation...

...M. V. Mikhailov; E. A. Mikhailova; S. J. H. Ashcroft The ATP-sensitive potassium (K ATP ) channel plays a key role in controlling β-cell membrane potential and insulin secretion. The channels are composed of two subunits, Kir6.2, which forms the channel pore, and SUR1, which contains binding sites...