Leptin-Linked Gene Reverses Diabetes in Mice (CME/CE): “The hunger hormone leptin can reverse diabetes (MedPage Today) — at least in mice — without causing weight loss, researchers have discovered.”
Antidiabetic Effects of IGFBP2, a Leptin-Regulated Gene
Cell Metabolism, Volume 11, Issue 1, 11-22, 6 January 2010
Kristina Hedbacker1, Kıvanç Birsoy1, Robert W. Wysocki1, 2, Esra Asilmaz1, Rexford S. Ahima3, 4, I. Sadaf Farooqi5 and Jeffrey M. Friedman1, 2, ,
Summary
We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma glucose and insulin concentration.
We found that a leptin dose of 12.5 ng/hr significantly lowers blood glucose and that 25 ng/hr of leptin normalizes plasma glucose and insulin without significantly reducing body weight, establishing that leptin exerts its most potent effects on glucose metabolism.
To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 (IGFBP2) as being regulated by leptin with a similarly high potency.
Overexpression of IGFBP2 by an adenovirus reversed diabetes in insulin-resistant ob/ob, Ay/a, and diet-induced obese mice, as well as insulin-deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a 3-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment of ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.