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

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Abstract
The effects of the hypoglycemic sulfonylurea glibenclamide (HB419) and the non-metabolizable Leu analog .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-labeling of the endogenous islet substrates was performed with [14C]glucose (20 mM) or [14C]Gln (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 cultured of islets with Gln. The rate of labeling of the islets with [14C]glucose reached an apparent plateau after 16 h 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 .apprx. 2.5%. Fractionation of lipids showed 67% phospholipids, 18% triacylglycerols, 11% diacylglycerols and 6% non-esterified fatty acid. The islet accumulation of Gln during 24 h corresponded to 11.5 .+-. 1.5 nmol/25 islets. After pre-labeling 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-labeling with [14C]Gln, whereas, in this latter situation, a significant stimulation was observed with BCH. The effects on the pancreatic .beta.-cells by antidiabetic sulfonylureas are not mediated via nutrient receptors.