MONDAY, Aug. 8 (HealthDay News) -- Leptin is associated with therapeutic benefits in the long-term treatment of mice with insulin-deficient nonobese diabetes, with a reduction in the onset and progression of glucose intolerance and diabetes complications, and an improvement in longevity, according to an experimental study published online Aug. 1 in Diabetes.
Masaki Naito, from the Kyoto University Graduate School of Medicine in Japan, and colleagues investigated the long-term effects of leptin on glucose metabolism, diabetes complications, and longevity in an insulin-dependent Akita mice diabetes model. Akita mice with physiological hyperleptinemia (LepTg:Akita) were produced by cross-mating Akita mice with leptin-expressing transgenic (LepTg) mice. Glucose and insulin tolerance tests and pair-fed studies were performed, and metabolic parameters were monitored for 10 months. Histological studies of the pancreata and kidneys were performed. The plasma levels and pancreatic contents of insulin and glucagon, plasma levels of lipids and plasma glucagon, and urinary albumin excretion were estimated, and survival rates calculated.
The investigators identified severe hyperglycemia in Akita mice, and hyperphagia from weaning stage, but normoglycemia was identified after an extended fast in LepTg:Akita mice even at 10 months of age. Throughout the study, the LepTg:Akita mice had half the six-hour fasting blood glucose level of Akita mice. LepTg:Akita mice's food intake was suppressed to a level comparable to wild type mice, but the blood glucose levels in Akita mice remained unaffected by pair feeding. Throughout the follow-up, LepTg:Akita mice exhibited better glucose tolerance and insulin hypersensitivity than Akita mice. LepTg:Akita mice had normal plasma glucagon levels and urinary albumin excretion rates. The median mortality time for Akita mice was 12 months, and all LepTg:Akita mice survived longer than that.
"The current study demonstrates that leptin has a therapeutic impact on the onset and progression of glucose intolerance, diabetes complications, and longevity in a mouse model of insulin-deficient nonobese diabetes," the authors write.
The study was partially funded by Lilly and Novo Nordisk.
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