Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation

作者：Ribeiro da Silva Priscilla Muniz; Batista Thiago Martins; Ribeiro Rosane Aparecida; Zoppi Claudio Cesar; Boschero Antonio Carlos; Carneiro Everardo Magalhaes^*

来源：Metabolism-Clinical and Experimental, 2012, 61(5): 721-732.

DOI：10.1016/j.metabol.2011.09.012

We herein studied the role of glutamate dehydrogenase (GDH), in response to leucine (LEU) supplementation, upon insulin secretion of malnourished rats. Weaned male Wistar rats were fed normal-protein (17%) or low-protein diet (6%, LP) for 8 weeks. Half of the rats of each group were supplemented with LEU (1.5%) in the drinking water for the following 4 weeks. Gene and protein expressions, static insulin secretion, and cytoplasmic Ca2+ oscillations were measured. Glutamate dehydrogenase messenger RNA was 58% lower in LP islets, and LEU supplementation augmented it in 28%. The LP islets secreted less insulin when exposed to 20 mmol/L LEU, 20 mmol/L LEU + 2 mmol/L glutamine (with or without 5 mmol/L aminooxyacetic acid, a branched chain aminotransferase inhibitor, or 20 mu mol/L epigallocatechin gallate, a GDH inhibitor), 20 mmol/L alpha-ketoisocaproate, glutamine + 20 mmol/L beta-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (a GDH activator), and 22.2 mmol/L glucose. Leucine supplementation augmented insulin secretion to levels found in normal-protein islets in all the above conditions, an effect that was blunted when islets were incubated with epigallocatech in gallate. The glutamine + beta-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid-induced increased (Ca2+](i) and oscillations were higher than those for LP islets. Leucine supplementation normalized these parameters in LP islets. Impaired GDH function was associated with lower insulin release in LP islets, and LEU supplementation normalized insulin secretion via restoration of GDH function. In addition, GDH may contribute to insulin secretion through ameliorations of Ca2+ handling in LP islets.

• 出版日期2012-5