Leptin produced by fat cells aids in treating diabetes

Leptin produced by fat cells aids in treating diabetes

UC Davis researchers looking for alternatives to insulin

Story by Hudson Lofchie
Image from Wikipedia Commons

Published in The California Aggie (theaggie.org) on September 28, 2011

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Researchers at UC Davis recently published a paper detailing new treatments that use the hormone leptin, instead of insulin, to treat patients with Type 1 and Type 2 diabetes (juvenile onset and adult onset, respectively).

The research came from multiple sources including the School of Veterinary Medicine, the Department of Nutrition and the University of Washington School of Medicine.

“Leptin improves blood sugar control by increasing sensitivity to insulin,” said Bethany Cummings, a veterinary molecular physiologist at UC Davis and co-author of the paper. Leptin is produced by the bodies’ fat cells and regulates appetite and fat metabolism.

Leptin decreases appetite by signaling the brain to stop food intake. When it was discovered in the 1990s, it was used as a diet drug and appetite suppressant.

Aside from the health benefits of decreasing appetite, the research team was focused on leptin’s other beneficial effects – reducing circulating triglycerides and lowering blood sugar levels. Triglycerides, or fatty acids, circulate in the body and at high levels can cause heart disease. Leptin also works to increase sensitivity by reducing stress in the endoplasmic reticulum (ER) – the part of the cell where proteins are made.

“Leptin can reduce ER stress, which causes insulin resistance, by lowering glucagon, a hormone that causes the liver to release sugar into the blood,” said Peter Havel, a veterinary endocrinologist at UC Davis and lead author of the paper.

To conduct the necessary experiments, the researchers used a special breed of rat called the UCD-T2DM, or UC Davis Type 2 Diabetes Mellitus rat. This breed of rat was created at UC Davis to simulate as closely as possible the physiological conditions of diabetes in humans. The T2DM rat is a cross of the Sprague Dawley rat (the standard laboratory rat) bred for obesity, and lean Zucker Diabetic Fatty rats. Neither of these rats get diabetes on their own, but when their traits are combined, it creates a high susceptibility to Type 2 diabetes.

One group of rats was treated with twice-daily injections of leptin, while a control group received no injections. The leptin-treated group was able to survive without any insulin treatment, showing that leptin may prove to be a viable alternative to insulin.

Unfortunately, leptin is far more expensive than insulin, even though both are made from the same recombinant DNA process. According to a sales representative at Abcam, a recombinant protein manufacturer, leptin costs $325 for just one milligram. Insulin costs $90 for about a 10-day supply for a Type 1 diabetic.

Even with the higher cost, leptin is a potential treatment for insulin-resistant Type 2 diabetics who are at risk for transitioning to insulin-deficient Type 1 diabetes. By creating alternative treatments for diabetes, patients can avoid many of the unpleasant complications arising from poor diabetes control.

Diabetes affects 25.8 million people in the United States, 8.3 percent of the total population. According to the U.S. Department of Health and Human Services, diabetes costs the U.S. $58 billion per year in work loss, premature mortality and disability. Health complications related to diabetes – such as heart disease, stroke, hypertension, blindness and amputations – result from fluctuating and heightened blood sugar levels.

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