Duplomb Laurence, Lee Young, Wang May-Yun, Park Byung H, Takaishi Kiyosumi, Agarwal Anil K, Unger Roger H
Gifford Laboratories, Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Biochem Biophys Res Commun. 2004 Jan 16;313(3):594-9. doi: 10.1016/j.bbrc.2003.11.160.
To determine if increased local production of glucocorticoids by the pancreatic islets might play a role in the spontaneous noninsulin-dependent diabetes mellitus of obesity, we compared islet 11beta-HSD-1 mRNA and activity in islets of obese prediabetic and diabetic Zucker Diabetic Fatty (ZDF) (fa/fa) rats and lean wild-type (+/+) controls. In diabetic rat islets, both mRNA and enzymatic activity of the enzyme were increased in proportion to the hyperglycemia. Troglitazone (TGZ) treatment, beginning at 6 weeks of age, prevented the hyperglycemia, the hyperlipidemia, and the increase in 11beta-HSD-1. To determine if the metabolic abnormalities had caused the 11beta-HSD-1 increase, prediabetic islets were cultured in high or low glucose or in 2:1 oleate:palmitate for 3 days. Neither nutrient enhanced the expression of 11beta-HSD-1. We conclude that 11beta-HSD-1 expression and activity are increased in islets of diabetic, but not prediabetic ZDF rats, and that TGZ prevents both the increase in 11beta-HSD-1 and the diabetes.
为了确定胰岛局部糖皮质激素生成增加是否可能在肥胖相关的自发性非胰岛素依赖型糖尿病中发挥作用，我们比较了肥胖的糖尿病前期和糖尿病Zucker糖尿病脂肪大鼠（ZDF，fa/fa）以及瘦的野生型对照大鼠（+/+）胰岛中11β-羟基类固醇脱氢酶1（11β-HSD-1）的mRNA水平和活性。在糖尿病大鼠胰岛中，该酶的mRNA和酶活性均与高血糖成比例增加。从6周龄开始用曲格列酮（TGZ）治疗，可预防高血糖、高血脂以及11β-HSD-1的增加。为了确定代谢异常是否导致了11β-HSD-1增加，将糖尿病前期胰岛在高糖或低糖或2:1油酸:棕榈酸中培养3天。两种营养物质均未增强11β-HSD-1的表达。我们得出结论，11β-HSD-1的表达和活性在糖尿病ZDF大鼠的胰岛中增加，但在糖尿病前期ZDF大鼠胰岛中未增加，并且TGZ可预防11β-HSD-1的增加和糖尿病。
