VMH损伤大鼠和肥胖Zucker大鼠胰岛中胰岛淀粉样多肽分泌过多。

Hypersecretion of IAPP from the islets of VMH-lesioned rats and obese Zucker rats.

作者信息

Tokuyama Y, Kanatsuka A, Ohsawa H, Yamaguchi T, Makino H, Yoshida S, Nagase H, Inoue S

机构信息

Second Department of Internal Medicine, Chiba University School of Medicine, Japan.

出版信息

Diabetes Res Clin Pract. 1992 Jan;15(1):23-9. doi: 10.1016/0168-8227(92)90063-w.

DOI:10.1016/0168-8227(92)90063-w

PMID:1541231

Abstract

To investigate the possible role of islet amyloid polypeptide (IAPP) in the development of type 2 diabetes mellitus, we examined the IAPP content and secretion in pancreatic islets isolated from ventromedial hypothalamic (VMH)-lesioned rats and genetically obese Zucker rats, using a specific radioimmunoassay for IAPP. Obesity and hyperinsulinemia were observed in rats 21 days after VMH lesioning. IAPP content was increased in the islets of VMH-lesioned rats compared with findings in the sham-operated controls (100.9 +/- 6.6 vs 72.8 +/- 3.85 fmol/islet; P less than 0.01). Isolated islets of VMH-lesioned rats secreted larger amounts of IAPP in the presence of 2.8 and 16.7 mM glucose (2.99 +/- 0.98 and 11.2 +/- 0.29 fmol islet-1 3 h-1) than was noted in sham-operated rats (ND and 6.65 +/- 0.78 fmol islet-1 3 h-1). In the obese Zucker rats, aged 14 weeks, IAPP concentrations in the islets were elevated compared with lean rats (133.3 +/- 10.6 vs 84.4 +/- 8.5 fmol/islet; P less than 0.01). The isolated islets secreted larger amounts of IAPP in response to 2.8 and 16.7 mM glucose (2.83 +/- 0.88 and 15.81 +/- 1.35 fmol islet-1 3 h-1) than did those from lean control rats (0.36 +/- 0.19 and 12.49 +/- 1.20 fmol islet-1 3 h-1). These results strongly suggest that overproduction and hypersecretion of IAPP occur in animals with obesity and hyperinsulinemia.

摘要

为了研究胰岛淀粉样多肽（IAPP）在2型糖尿病发生发展过程中可能发挥的作用，我们采用针对IAPP的特异性放射免疫分析法，检测了从腹内侧下丘脑（VMH）损伤大鼠和遗传性肥胖Zucker大鼠分离出的胰岛中IAPP的含量及分泌情况。VMH损伤后21天的大鼠出现了肥胖和高胰岛素血症。与假手术对照组相比，VMH损伤大鼠胰岛中的IAPP含量增加（分别为100.9±6.6和72.8±3.85 fmol/胰岛；P<0.01）。在2.8和16.7 mM葡萄糖存在的情况下，VMH损伤大鼠分离出的胰岛分泌的IAPP量更大（分别为2.99±0.98和11.2±0.29 fmol胰岛⁻¹ 3 h⁻¹），而假手术大鼠分泌量未检测到及为6.65±0.78 fmol胰岛⁻¹ 3 h⁻¹。在14周龄的肥胖Zucker大鼠中，胰岛中的IAPP浓度高于瘦大鼠（分别为133.3±10.6和84.4±8.5 fmol/胰岛；P<0.01）。分离出的胰岛在2.8和16.7 mM葡萄糖刺激下分泌的IAPP量更大（分别为2.83±0.88和15.81±1.35 fmol胰岛⁻¹ 3 h⁻¹），而瘦对照大鼠分离出的胰岛分泌量为0.36±0.19和12.49±1.20 fmol胰岛⁻¹ 3 h⁻¹。这些结果有力地表明，肥胖和高胰岛素血症动物中存在IAPP的过度产生和分泌过多现象。