| First Author | Wang Y | Year | 2015 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 308 |
| Issue | 1 | Pages | E84-95 |
| PubMed ID | 25389364 | Mgi Jnum | J:218524 |
| Mgi Id | MGI:5617878 | Doi | 10.1152/ajpendo.00205.2014 |
| Citation | Wang Y, et al. (2015) 11beta-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue. Am J Physiol Endocrinol Metab 308(1):E84-95 |
| abstractText | Long-term glucocorticoid exposure increases the risk for developing type 2 diabetes. Prereceptor activation of glucocorticoid availability in target tissue by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic syndrome. We explored whether the tissue-specific modulation of 11beta-HSD1 and H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and lipolysis and analyzed the effects of 11beta-HSD1 inhibition on the key lipid metabolism genes and insulin-signaling cascade. We observed that corticosterone (CORT) treatment increased expression of 11beta-HSD1 and H6PDH and induced lipase HSL and ATGL with suppression of p-Thr(172) AMPK in adipose tissue of C57BL/6J mice. In contrast, CORT induced adipose insulin resistance, as reflected by a marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr(308) Akt/PKB. Furthermore, 11beta-HSD1 shRNA attenuated CORT-induced 11beta-HSD1 and lipase expression and improved insulin sensitivity with a concomitant stimulation of pThr(308) Akt/PKB and p-Thr(172) AMPK within adipose tissue. Addition of CORT to 3T3-L1 adipocytes enhanced 11beta-HSD1 and H6PDH and impaired p-Thr(308) Akt/PKB, leading to lipolysis. Knockdown of 11beta-HSD1 by shRNA attenuated CORT-induced lipolysis and reversed CORT-mediated inhibition of pThr(172) AMPK, which was accompanied by a parallel improvement of insulin signaling response in these cells. These findings suggest that elevated adipose 11beta-HSD1 expression may contribute to glucocorticoid-induced insulin resistance and adipolysis. |
