Alteration of 11beta-hydroxysteroid dehydrogenase type 1 in skeletal muscle in a rat model of type 2 diabetes.
Recent investigations have demonstrated that activation of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in liver and adipose tissue is closely related to the pathogenesis of obesity and diabetes. However, the relationship between alteration of 11beta-HSD1 and the pathogenesis of type 2 diabetes in skeletal muscle is still unclear. A rat model of Type 2 diabetes was developed by high fat diet feeding combined with multiple low dose streptozotocin injection (30 mg/kg, i.p. twice). Intraperitoneal glucose tolerance test, insulin tolerance test were performed. Fasting blood glucose, fasting insulin, total cholesterol, triglyceride were measured. The protein and mRNA level of 11beta-HSD1 and glucocorticoid receptor in gastrocnemius muscle were determined. The alteration of insulin signaling pathway related protein was investigated. We found that the protein levels of 11beta-HSD1 and glucocorticoid receptor were significantly increased (P < 0.05); the mRNA level of 11beta-HSD1 was also elevated (P < 0.05); the mRNA level of glucocorticoid receptor was decreased (P < 0.05). After insulin stimulation, diabetic rats had no significant changes in the level of the insulin receptor beta-subunit (IR-beta), AKT, as in phosphorylated AKT in the gastrocnemius muscle compared to its basal state. Similar results were observed in the protein expression level of glucose transporter 4 (GLUT4). Our data indicate that the alteration of 11beta-HSD1 at protein and mRNA level may be related to the abnormality of insulin signal pathway in skeletal muscle, this effect may be mediated by glucocorticoid receptor.
Zhang
Ming
M
Department of Pharmacology, School of Basic Medical Sciences, Jilin University, Changchun, Jilin, Jilin, 130021, China.
Lv
Xiao-Yan
XY
Li
Jing
J
Xu
Zhi-Gang
ZG
Chen
Li
L
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000473:pathology; D007328:Insulin / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics; D015398:Signal Transduction
D007328:Insulin; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D011972:Receptor, Insulin