β-cells with relative low himp1 overexpression levels in a transgenic mouse line enhance basal insulin production and hypoxiahypoglycemia toleranceβ-cells相对低himp1超表达水平转基因小鼠行加强基础胰岛素的分泌和hypoxiahypoglycemia宽容.pdfVIP

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β-cells with relative low himp1 overexpression levels in a transgenic mouse line enhance basal insulin production and hypoxiahypoglycemia toleranceβ-cells相对低himp1超表达水平转基因小鼠行加强基础胰岛素的分泌和hypoxiahypoglycemia宽容.pdf

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β-cells with relative low himp1 overexpression levels in a transgenic mouse line enhance basal insulin production and hypoxiahypoglycemia toleranceβ-cells相对低himp1超表达水平转基因小鼠行加强基础胰岛素的分泌和hypoxiahypoglycemia宽容

b-Cells with Relative Low HIMP1 Overexpression Levels in a Transgenic Mouse Line Enhance Basal Insulin Production and Hypoxia/Hypoglycemia Tolerance 1 2 3¤ 3 1 1 Xiaoping Zhang , Linda Degenstein , Yun Cao , Jeffrey Stein , Kwame Osei , Jie Wang * 1 Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America, 2 Transgenic Core, The University of Chicago, Chicago, Illinois, United States of America, 3 Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America Abstract Rodent pancreatic b-cells that naturally lack hypoglycemia/hypoxia inducible mitochondrial protein 1 (HIMP1) are susceptible to hypoglycemia and hypoxia influences. A linkage between the hypoglycemia/hypoxia susceptibility and the lack of HIMP1 is suggested in a recent study using transformed b-cells lines. To further illuminate this linkage, we applied mouse insulin 1 gene promoter (MIP) to control HIMP1-a isoform cDNA and have generated three lines (L1 to L3) of heterozygous HIMP1 transgenic (Tg) mice by breeding of three founders with C57BL/6J mice. In HIMP1-Tg mice/islets, we performed quantitative polymerase chain reaction (PCR), immunoblot, histology, and physiology studies to investigate HIMP1 overexpression and its link to b-cell function/survival and body glucose homeostasis. We found that the HIMP1 level increased steadily in b-cells of L1 to L3 heterozygous HIMP1-Tg mice. HIMP1 overexpression at relatively lower levels in L1 heterozygotes results in a negligible decline in blood glucose concentrations and an insignificant elevation in blood insulin levels, while HIMP1 overexpression at higher levels are t