Leptin Can Replace Insulin to Treat Type 1 Diabetes

Researchers have shown that leptin can replace insulin for treating terminally ill animals in a rodent model of type 1 diabetes.

Leptin is a 16-kDa-protein hormone that plays a key role in regulating energy intake and expenditure, including decreasing of appetite and increasing of metabolism. In the current study, investigators from the University of Texas Southwestern Medical Center (Dallas, TX, USA) used gene therapy techniques to overexpress leptin in a line of insulin-deficient mice. At the beginning of the study, the animals were terminally ill with uncontrolled diabetes due to autoimmune or chemical destruction of beta cells.

To render the animals hyperleptinemic they were injected with an adenovirus carrying the leptin gene. Results published in the September 8, 2008, online issue of the Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that within about 10 days the animals' severe hyperglycemia and ketosis were corrected. Despite the lack of insulin, the animals resumed linear growth and appeared normal. Untreated control animals died within two or three days, while the treated rodents were maintained for 25 weeks.

The mechanism of leptin's glucose-lowering action involved the suppression of glucagon, a hormone produced by the pancreas that raises glucose levels. Normally, glucagon is released when the glucose level in the blood is low. In insulin deficiency, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream.

"The fact that these animals do not die and are restored to normal health despite a total lack of insulin is hard for many researchers and clinicians to believe,” said senior author Dr. Roger Unger, professor of internal medicine at the University of Texas Southwestern Medical Center. "Many scientists, including us, thought it would be a waste of time to give leptin in the absence of insulin. We have been brainwashed into thinking that insulin is the only substance that can correct the consequences of insulin deficiency.”

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University of Texas Southwestern Medical Center