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Glucose and non-glucidic nutrients exert permissive effects on 2-keto acid regulation of pancreatic beta-cell function

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

McClenaghan, Neville and Flatt, Peter (1999) Glucose and non-glucidic nutrients exert permissive effects on 2-keto acid regulation of pancreatic beta-cell function. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1426 (1). pp. 110-118. [Journal article]

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Abstract

Insulin-releasing effects of straight and branched chain 2-keto acids were assessed using clonal glucose-responsive beta-cells. Pyruvic acid (PA), 2-ketovaleric acid (KV), 2-ketoisovaleric acid (KIV) or 2-keto-3-methylvaleric acid (KMV) dose-dependently promoted the stimulatory effects of D-glucose, whereas 2-ketobutyric acid (KB) did not affect insulin release. The stimulatory 2-keto acids also promoted the stimulatory activity of D-glyceraldehyde, L-leucine or L-arginine. Responses to PAI KV, KIV or KMV were significantly reduced by transport inhibition with 2-cyano-3 hydroxycinnamate, glucokinase inhibition with mannoheptulose or metabolic inhibition with sodium azide or sodium cyanide. Membrane hyperpolarisation with K+ depletion or diazoxide reduced insulin output, but failed to abolish secretory responses to KV, KIV and KMV. Secretory effects of these 2-keto acids also persisted in beta-cells depolarised with high KCI and glucose. Voltage-dependent Ca2+ channel blockade, with verapamil, or depletion of extracellular Ca2+ abolished the secretory activity of 2-keto acids. Collectively, these results indicate that glucose and metabolisable nutrients exert permissive effects on 2-keto acid-induced insulin release. In addition, KV. KIV and KMV can regulate beta-cell function at least partially independently of K+-ATP channel activity, both through their mitochondrial metabolism and regulation of Ca2+ influx. (C) 1999 Elsevier Science B.V. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:3117
Deposited By:Professor Peter Flatt
Deposited On:08 Jan 2010 15:10
Last Modified:15 Jun 2011 11:10

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