{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:36:29Z","timestamp":1791329789100,"version":"4.3.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:p>\n                    Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic \u03b2-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 \u03bcg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), amylin (A; 100 \u03bcg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), 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 AMPK\u03b12 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.\n                  <\/jats:p>","DOI":"10.1152\/ajpendo.00198.2011","type":"journal-article","created":{"date-parts":[[2012,1,25]],"date-time":"2012-01-25T01:42:57Z","timestamp":1327455777000},"page":"E924-E931","source":"Crossref","is-referenced-by-count":26,"title":["Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice"],"prefix":"10.1152","volume":"302","author":[{"given":"Toru","family":"Kusakabe","sequence":"first","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Ebihara","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine; 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