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New mouse model sheds light on lipoatrophic diabetes

A collaboration of scientists from Harvard Medical School and Dartmouth Medical School has developed a new mouse model of lipoatrophic diabetes, and highlighted leptin therapy as a successful tool to combat this rare form of type II diabetes.

Lipoatrophic diabetes mellitus is characterized by a lack of subcutaneous fat (lipoatrophy), high blood sugar (hyperglycemia), and high blood insulin (hyperinsulinemia). Because patients with lipoatrophic diabetes are insulin-resistant, although high levels of insulin accumulate in their bloodstream, glucose is not efficiently delivered to their body's cells, eventually resulting in severe eye, kidney, nerve and cardiovascular problems. A relatively rare disease in humans, lipoatrophic diabetes is thought to have a strong genetic component.

With the new model of lipoatrophic diabetes that Dr. Ronald Kahn and colleagues have developed, scientists are gaining valuable insight into the genetic pathway of this disease. "This model also points out how two genetic traits, neither of which alone can produce diabetes, can interact to produce a very severe diabetic state," states Dr. Kahn.

Dr. Kahn and colleagues were interested in elucidating the roles of the four insulin receptor substrate protein family members (IRS-1, -2, -3, and 4; the substrates for the insulin and insulin-like growth factor receptors) in insulin signal transduction and metabolism. IRS single knock-out mice had been previously made, and although the IRS-3-deficient mice showed no abnormalities, and the IRS-4-deficient mice showed only slight growth retardation and glucose intolerance, mice deficient in IRS-1 or IRS-2 displayed severe (but different) phenotypes.

Dr. Kahn and colleagues suspected that in IRS single knock-out mice the presence of the remaining three functional IRS genes could possibly compensate for the loss of one IRS gene and thereby obscure its true physiological function. Thus, the researchers generated two diffe
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
14-Dec-2002


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