2-oxocarboxylic acids and function of pancreatic islets in obese-hyperglycaemic mice. Insulin secretion in relation to 45Ca uptake and metabolism.
The effects of aliphatic 2-oxocarboxylic acids, at concentrations of up to 40mm, on the function of pancreatic islets from ob/ob (obese-hyperglycaemic) mice were investigated. 1. 2-Oxopentanoate, dl-3-methyl-2-oxopentanoate, 4-methyl-2-oxopentanoate and 2-oxohexanoate all induced insulin release by isolated incubated islets and a biphasic insulin-secretory pattern in perfused mouse pancreas. The last two substances were similar in potency to glucose. Pyruvate, 2-oxobutyrate, 3-methyl-2-oxobutyrate and 2-oxo-octanoate did not induce insulin release significantly. 2. 2-Oxocarboxylic acids with significant insulin-secretory potency also induced significant (45)Ca uptake by isolated incubated islets. 3. The rates of decarboxylation of [1-(14)C]pyruvate, 3-methyl-2-oxo[1-(14)C]butyrate and 4-methyl-2-oxo[1-(14)C]pentanoate were twice as high as the rates of oxidation of the corresponding U-(14)C-labelled compounds. However, whereas the rates of metabolism of labelled pyruvate and 3-methyl-2-oxobutyrate steadily increased over the concentration range 1-40mm, those of labelled 4-methyl-2-oxopentanoate and d-[U-(14)C]glucose levelled off at concentrations above 10mm. 4. Omission of (40)CaCl(2) from the incubation medium reduced the rate of oxidation of the insulin secretagogue [U-(14)C]4-methyl-2-oxopentanoate, but left that of the non-(insulin secretagogue) [U-(14)C]3-methyl-2-oxobutyrate unaffected. 5. Only glucose, and not pyruvate, 3-methyl-2-oxobutyrate and 4-methyl-2-oxopentanoate, significantly inhibited oxidation of endogenous fatty acids. 6. It is suggested that stimulus-secretion coupling and the resulting exocytosis of insulin in pancreatic beta-cells may modulate both fuel oxidation and (45)Ca uptake.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese; D010477:Perfusion; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical
D005227:Fatty Acids; D007328:Insulin; D007651:Keto Acids; D005947:Glucose; D002118:Calcium