Leptin revives mice dying of type-1 diabetes

WASHINGTON - For the first time, terminally ill rodents with type-1 diabetes have been restored to complete health with a single injection of a substance other than insulin.

University of Texas Southwestern (UTS) researchers tested for the first time whether an injection of leptin gene given to insulin-deficient mice dying of diabetic coma could reverse their terminal condition.

After the injection, the animals began producing excessive amounts of leptin, which reversed consequences of type-1 diabetes including weight loss, hyperglycemia and ketoacidosis, a potentially fatal condition that develops when the body doesn’t have enough insulin to meet basic metabolic requirements.

Much of the effect was mediated by complete suppression of the high glucagon levels, said Xinxin Yu, assistant instructor of UTS internal medicine and co-author of the study.

‘These animals were actually dying,’ Yu said. ‘But if we gave them the leptin gene, within two weeks, the terminally ill rodents were restored to full health without any other treatment.’

Since the discovery of insulin in 1922, type-1 diabetes (insulin-dependent diabetes) in humans has been treated by injecting insulin to lower high blood sugar levels and prevent diabetic coma.

‘The fact that these animals don’t die and are restored to normal health despite a total lack of insulin is hard for many researchers and clinicians to believe,’ said Roger Unger, professor of internal medicine and senior study co-author.

‘Many scientists, including us, thought it would be a waste of time to give leptin in the absence of insulin. We’ve been brainwashed into thinking that insulin is the only substance that can correct the consequences of insulin deficiency.’

The mechanism of leptin’s glucose-lowering action appears to involve the suppression of glucagon, a hormone produced by the pancreas that raises glucose levels.

The next step is to study other potential glucagon suppressants and begin leptin clinical trials within the next year, said an UTS release.

These findings appear in the Proceedings of the National Academy of Sciences.

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