Holze S, Panten U
Biochim Biophys Acta. 1979 Dec 3;588(2):211-18. doi: 10.1016/0304-4165(79)90204-6.
alpha-Ketoisocaproic acid has been shown to be a potent insulin secretagogue but the mechanism has not been elucidated. To define the role of beta-cell metabolism in the insulinotropic activity of alpha-ketoisocaproic acid the utilization of glucose and the oxidation of alpha-ketoisocaproic and isovaleric acid by incubated islets of obese hyperglycemic mice were measured. Glucose metabolism was never enhanced by alpha-ketoisocaproic acid. The same 14CO2 amounts were released from the non-secretagogue [1-14C]isovaleric acid (10 mM) or from alpha-keto[2-14C]isocaproic acid (5--20 mM). Pyruvate (20 mM) did not inhibit alpha-ketoisocaproic acid-induced insulin secretion in spite of reduction of decarboxylation of alpha-ketoisocaproic acid by more than 40%. The results indicate that stimulated insulin release in response to alpha-ketoisocaproic acid is not mediated by an indirect increase in glucose metabolism and further suggest that isovaleryl-CoA and following CoA-esters in alpha-ketoisocaproic acid degradation are not likely recognized as signals. The possibility, however, remains that enhanced intramitochondrial production of reducing equivalents elicits insulin secretion.
α-酮异己酸已被证明是一种有效的胰岛素促分泌剂，但其作用机制尚未阐明。为了确定β细胞代谢在α-酮异己酸促胰岛素分泌活性中的作用，我们测量了肥胖高血糖小鼠胰岛在孵育过程中葡萄糖的利用以及α-酮异己酸和异戊酸的氧化情况。α-酮异己酸从未增强葡萄糖代谢。非促分泌剂[1-¹⁴C]异戊酸（10 mM）或α-酮[2-¹⁴C]异己酸（5 - 20 mM）释放的¹⁴CO₂量相同。尽管α-酮异己酸的脱羧作用减少了40%以上，但丙酮酸（20 mM）并未抑制α-酮异己酸诱导的胰岛素分泌。结果表明，α-酮异己酸刺激胰岛素释放并非由葡萄糖代谢的间接增加介导，进一步表明α-酮异己酸降解过程中的异戊酰辅酶A及后续的辅酶A酯不太可能被识别为信号。然而，线粒体内还原当量生成增加引发胰岛素分泌的可能性仍然存在。
