| First Author | Kusakabe T | Year | 2012 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 302 |
| Issue | 8 | Pages | E924-31 |
| PubMed ID | 22275759 | Mgi Jnum | J:184635 |
| Mgi Id | MGI:5425197 | Doi | 10.1152/ajpendo.00198.2011 |
| Citation | Kusakabe T, et al. (2012) Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice. Am J Physiol Endocrinol Metab 302(8):E924-31 |
| abstractText | Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic beta-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 mug.kg(-)(1).day(-)(1)), amylin (A; 100 mug.kg(-)(1).day(-)(1)), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKalpha2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes. |
