McClenaghan, Neville, Flatt, Peter and Bailey, CJ (1998) Insulin-releasing action of the novel antidiabetic agent BTS 67 582. BRITISH JOURNAL OF PHARMACOLOGY, 123 (3). pp. 400-404. [Journal article]
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1 BTS 67 582 (1,1-dimethyl-2-(2-morpholinophenyl)guan fumarate) is a novel antidiabetic agent with a short-acting insulin-releasing effect. This study examined its mode of action in the clonal B-cell line BRIN-BD11. 2 BTS 67 582 increased insulin release from BRIN-BD11 cells in a concentration-dependent manner (10(-8) to 10(-4) M) at both non-stimulating (1.1 mM) and stimulating (16.7 mM) concentrations of glucose. 3 BTS 67 582 (10(-4) M) potentiated the insulin-releasing effect of a depolarizing concentration of K+ (30 mM), whereas the K+ channel openers pinacidil (400 mu M) and diazoxide (300 mu M) inhibited BTS 67 582-induced release. 4 Suppression of Ca+ channel activity with verapamil (20 mu M) reduced the insulin-releasing effect of BTS 67 582 (10(-4) M). 5 BTS 67 582 (10(-4) M) potentiated insulin release induced by amino acids (10 mM), and enhanced the combined stimulant effects of glucose plus either the fatty acid palmitate (10 mM). or agents which raise intracellular cyclic AMP concentrations (25 mu M forskolin and 1 mM isobutylmethylxanthine), or the cholinoceptor agonist carbachol (100 mu M). 6 Inhibition of glucose-stimulated insulin release by adrenaline or noradrenaline (10 mu M) was partially reversed by BTS 67 582 (10(-4) M). 7 These data suggest that the insulin-releasing effect of BTS 67 582 involves regulation of ATP-sensitive K+ channel activity and Ca2+ influx, and that the drug augments the stimulant effects of nutrient insulin secretagogues and agents which enhance adenylate cyclase and phospholipase C. BTS 67 582 may also exert insulin-releasing effects independently of ATP-sensitive K+ channel activity.
|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
|Deposited By:||Professor Peter Flatt|
|Deposited On:||08 Jan 2010 14:01|
|Last Modified:||15 Jun 2011 11:10|
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