title: Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes.
abstract: Pancreatic beta-cell is responsible for insulin secretion in response to the availability of nutrients. Type 2 diabetes mellitus (T2D) is the result of pancreatic b-cell failure to supply sufficient amount of insulin accompanied with decreased sensitivity of the body tissues to respond to insulin. The insulin secretion apparatus of beta-cell is uniquely equipped with multiple metabolic and signaling steps that are under rigorous control. The metabolic machinery of beta-cell is designed to sense the fluctuations in blood glucose level and supply insulin accordingly to the needs of body. Besides glucose, amino acids including glutamine and leucine and also fatty acids are known to either stimulate the beta-cell directly or potentiate the glucose stimulated insulin secretion (GSIS) response. Glucose metabolism dependent GSIS is linked with the production of ATP that is needed for K+ATP channel inhibition and influx of calcium, necessary for insulin granule exocytosis. Besides glucose metabolism, amino acid metabolism and lipid metabolism derived metabolites mediate the optimal glucose response of beta-cells to secrete insulin. Metabolites derived from nutrient secretagogues that directly or indirectly participate in the enhancement of GSIS are considered as metabolic coupling factors. In this review, we will discuss the regulation of insulin secretion by b-cell keeping the recent developments in metabolic signaling in focus. The relevant metabolic pathways in pancreatic beta-cell and their role in the control of fuel-stimulated insulin secretion will be reviewed to arrive at a consensus picture with respect to the metabolic signaling of insulin secretion.
authors: Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College; The Affiliated Xuzhou Hospital of Medical College of Southeast University, Jiangsu, China. mwlj521@163.com.
authors: C-Y
authors: CY
authors: Zou
authors: Y
authors: Y
authors: Gong
authors: J
authors: J
authors: Liang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000596:Amino Acids; D007328:Insulin; D005947:Glucose