Leucine metabolism in regulation of insulin secretion from pancreatic beta cells

Leucine, a branched-chain amino acid that must be supplied in the daily diet, plays an important role in controlling protein synthesis and regulating cell metabolism in various cell types. In pancreatic beta cells, leucine acutely stimulates insulin secretion by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. Leucine has also been shown to regulate gene transcription and protein synthesis in pancreatic islet beta cells via both mTOR-dependent and -independent pathways at physiological concentrations. Long-term treatment with leucine has been shown to improve insulin secretory dysfunction of human diabetic islets via upregulation of certain key metabolic genes. In vivo, leucine administration improves glycemic control in humans and rodents with type 2 diabetes. This review summarizes and discusses the recent findings regarding the effects of leucine metabolism on pancreatic beta-cell function.