Differential changes in islet amyloid polypeptide (Amylin) and insulin mRNA expression after high-fat diet-induced insulin resistance in C57BL/6J mice
Differential changes in islet amyloid polypeptide (Amylin) and insulin mRNA expression after high-fat diet-induced insulin resistance in C57BL/6J mice
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DOI：
10.1053/meta.2000.18511
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发表时间：
2000-12-01
影响因子：
9.8
通讯作者：
Ahrén, B
中科院分区：
文献类型：
--
作者：
Mulder, H;Mårtensson, H;Ahrén, B
胰岛淀粉样蛋白是由胰岛淀粉样多肽（IAPP或amylin）衍生而来的，常发生于2型糖尿病.这种肽用于淀粉样蛋白形成的可用性可以通过增加IAPP的胰岛表达来增强。在胰岛素抵抗状态下，通过胰岛素分泌过多来维持血糖正常。受葡萄糖调节的IAPP表达或其与胰岛素的比例是否因与胰岛素抵抗相关的代谢紊乱而改变尚不清楚。因此，我们研究了胰岛素抵抗倾向的C57 BL/6 J小鼠胰岛IAPP和胰岛素mRNA的表达。因此，经过长期（48周）的挑战与高脂肪饮食（58%的脂肪热量基础相比，11%的控制饮食）高血糖症，高胰岛素血症，高脂血症，和高瘦素血症演变的小鼠。腹膜内（IP）葡萄糖耐量试验显示葡萄糖处置明显受损。此外，高脂喂养小鼠的血浆IAPP水平升高（11.3 +/- 1.2 vs 2.1 +/- 0.6 pmol/L，P <0.001）。定量原位杂交显示高脂喂养的小鼠中细胞质量增加，如胰岛IAPP和胰岛素mRNA标记的面积增加约50%所证明。两组中每个胰岛细胞的IAPP mRNA表达保持不变。与此相反，在高脂喂养的小鼠中，每个细胞的胰岛素mRNA表达显著降低（P <0.001）。因此，我们得出结论，C57 BL/6 J小鼠长期高脂喂养后的葡萄糖耐受不良伴随着胰岛素细胞表达的减少，但IAPP没有。IAPP与胰岛素表达的比率增加可能是携带淀粉样蛋白形成形式IAPP的物种中高脂肪饮食的淀粉样蛋白形成的基础。Copyright（C）2000 by W.B.桑德斯公司
Islet amyloid, derived from islet amyloid polypeptide (IAPP or amylin), frequently occurs in type 2 diabetes. Availability of this peptide for amyloid formation may be enhanced by increased islet expression of IAPP. In the insulin resistant state, euglycemia is maintained by hypersecretion of insulin. Whether IAPP expression, which is regulated by glucose, or its ratio to that of insulin is altered by the metabolic perturbations associated with insulin resistance is not known. Therefore, we studied islet expression of IAPP and insulin mRNA in insulin resistance-prone C57BL/6J mice. Thus, after a long-term (48 weeks) challenge with a high-fat diet (58% fat on a caloric base compared with 11% in the control diet) hyperglycemia, hyperinsulinemia, hyperlipidemia, and hyperleptinemia evolved in the mice. An intraperitoneal (IP) glucose tolerance test showed a marked impairment of glucose disposal. Also, plasma IAPP levels were elevated in high-fat fed mice (11.3 +/- 1.2 v 2.1 +/- 0.6 pmol/L, P < .001). Quantitative in situ hybridization showed increased -cell mass in high-fat fed mice, as evidenced by approximately 50% increase in area labeled for islet IAPP and insulin mRNA. IAPP mRNA expression per islet cell remained unchanged in both groups. In contrast, insulin mRNA expression per cell was significantly decreased in the high-fat fed mice (P < .001). We therefore conclude that glucose intolerance after long-term high-fat feeding in C57BL/6J mice is accompanied by reduced cellular expression of insulin, but not of IAPP. The increased ratio of IAPP versus insulin expression might underlie the amyloidogenicity of high-fat diet in species carrying an amyloidogenic form of IAPP. Copyright (C) 2000 by W.B. Saunders Company.