Editors' ChoiceType 1 Diabetes

Could Leptin Be Used to Treat Type 1 Diabetes?

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Science Translational Medicine  24 Mar 2010:
Vol. 2, Issue 24, pp. 24ec47
DOI: 10.1126/scitranslmed.3001076

Leptin—a hormone secreted by fat cells at levels that correlate with the amount of adipose tissue in the body—plays a key role in energy metabolism. Leptin deficiency leads to obesity, excess levels of circulating insulin, and insulin resistance, all of which are hallmarks of type 2 diabetes. Initially, much hope was pinned on the idea of leptin being a cure for obesity and type 2 diabetes, but that hope has not been realized because these conditions are associated with leptin resistance. Type 1 diabetes, which is caused by absolute insulin deficiency rooted in the autoimmune destruction of insulin-producing pancreatic beta cells, is not associated with leptin deficiency or obesity per se. Indeed, in some respects the metabolic effects of leptin and insulin oppose each other. For example, insulin suppresses lipid breakdown and induces lipid synthesis, whereas leptin does the reverse. Thus, the idea of treating type I diabetes with leptin seems astonishing, but Wang et al. now confirm earlier studies that show leptin is as effective as insulin in controlling type 1 diabetes in a mouse model of this disease.

These researchers show that leptin does not reverse insulin deficiency but instead corrects high blood sugar in the absence of insulin. Like insulin, leptin normalizes levels of glucagon (a hormone involved in carbohydrate metabolism), ketone bodies (by-products of fatty acid breakdown and a potential sign of diabetes), and blood lipids and increases lean body mass. Leptin’s negative effects on lipid synthesis may be the key to its metabolic benefits and its advantages as compared with insulin. Although many questions remain about how leptin replaces insulin action in absolute insulin deficiency, these results suggest that leptin might be combined with insulin as a therapy for type 1 diabetes.

M.-Y. Wang et al., Leptin therapy in insulin-deficient type I diabetes. Proc. Natl. Acad. Sci. U.S.A. 1 March 2010 (10.1073/pnas.0909422107). [Full Text]

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