Effect of a hypoglycaemic sulphonylurea (HB419) and a non-metabolizable amino acid (BCH) on the insulin release and endogenous substrate metabolism of rat pancreatic islets.
The effects of the hypoglycaemia sulphonylurea glibenclamide (HB419) and the non-metabolizable leucine analogue beta-2-aminobicyclo(2.2.1)heptane-2-carboxylic acid (BCH) on insulin release and endogenous substrate metabolism were studied in isolated rat islets. Pre-labelling of the endogenous islet substrate was performed with [14C]glucose (20 mM) or [14C]glutamine (10 mM) during a 24 h tissue culture period before measurements of insulin release or 14CO2 production in short-term incubations. Both HB419 and BCH stimulated the insulin release of the cultured islets, although BCH only after culture of islets with glutamine. The rate of labelling of the islets with [14C]glucose reached an apparent plateau after 16 h in culture and the total islet accumulation of glucose carbon over the 24 h period averaged 12.9 +/- 3.0 nmol/25 islets. Less than 0.5% of the glucose residues was converted to glycogen whereas lipids represented about 2.5%. Fractionation of lipids showed 67% phospholipids, 18% triacylglycerols, 11% diacylglycerols and 6% non-esterified fatty acid. The islet accumulation of glutamine during 24 h corresponded to 11.5 +/- 1.5 nmol/25 islets. After pre-labelling of islets with [14C]glucose there was no effect on the 14CO2-evolution over a 30 min incubation period of either HB419 or BCH. There was also no effect of HB419 after pre-labelling with [14C]glutamine, whereas, in this latter situation, a significant stimulation was observed with BCH. It is concluded that the effects on the pancreatic B-cells by antidiabetic sulphonylureas are not mediated via nutrient receptors.
D000596:Amino Acids / Q000494:pharmacology*; D000598:Amino Acids, Cyclic; D000818:Animals; D002245:Carbon Dioxide / Q000096:biosynthesis; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D007328:Insulin; D005973:Glutamine; D002245:Carbon Dioxide; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; D006003:Glycogen; D005947:Glucose; D005905:Glyburide