Joslin researchers uncover potential role of leptin i...( BOSTONOctober 1 2007A new Joslin-le...)

BOSTONOctober 1, 2007A new Joslin-led study has shown that leptin, a hormone known mainly for regulating appetite control and energy metabolism, plays a major role in islet cell growth and insulin secretion. This finding opens up new avenues for studying leptin and its role in islet cell biology, which may lead to new treatments for diabetes. This study appears in the October 2007 issue of The Journal of Clinical Investigation.

Previous in vitro studies suggested that leptin receptors, which are found in tissues throughout the body including the pancreas as well as the brain, mediate leptin-induced inhibition of insulin secretion in islet cells, also known as beta cells. We wanted to further our understanding of leptin and its role in beta cells independent of its effects in the brain, said Rohit N. Kulkarni, M.D., Ph.D., principal investigator at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School, who led this study. It is currently not known why obese individuals exhibit a high incidence of diabetes despite high levels of both insulin and leptin circulating in the bloodstream.

To understand the role of leptin in the islets, researchers developed a mouse model (known as a knock out or KO mouse) genetically engineered not to produce leptin receptors in the pancreas, while maintaining the receptors in the brain and the rest of the body. Researchers found that the mice lacking leptin receptors in the pancreas showed improved glucose tolerance and greater insulin secretion and beta cell growth. Since the normal function of leptin is to keep insulin levels from getting too high, the lack of leptin enhances insulin action in the beta cells and promotes insulin secretion, which was the result we expected, said Dr. Kulkarni.

In the second part of the study, the KO mice and a control group of mice with intact leptin receptors were placed on a high-fat diet. Although both the control and KO mice becam
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