Glucose stimulation of protein acylation in the pancreatic β-cell

[摘要] Aims: To determine whether protein acylation plays a role in the effects of glucose on the insulin secreting beta-cell. Main methods: The measurement of H-3-palmitate incorporation into protein in the INS 832/13 cell that has a robust and well-characterized biphasic insulin secretory response to stimulation with glucose. Key findings: Stimulating the cells with glucose increased the incorporation of H-3-palmitic acid into protein by up to 90%. Similarly, 2-aminobicyclo [2.2.1] heptane-2-carboxylic acid (BCH) the non-metabolizable analog of leucine that mimics the stimulatory effect of glucose on insulin secretion also increased the incorporation of H-3-palmitic acid into protein. Treatment of cell lysates with hydroxylamine substantially reduced the incorporation indicating that most of the incorporation was due to enzymatic palmitoylation of proteins. Cerulenin, a classical inhibitor of protein acylation also substantially reduced the incorporation. Using PAGE and autoradiography a glucose-induced increase in protein palmitoylation and specific glucose-induced increases in the palmitoylation of proteins of 30, 44, 48 and 76 kD were identified. Significance: The data suggest that protein acylation plays multiple roles in beta-cell function. (C) 2010 Elsevier Inc. All rights reserved.

[发布日期] 2010-12-18

[关键词] Glucose;Biphasic insulin secretion;Signaling pathways;Protein acylation