Study in PNAS reversed symptoms in terminally ill rodents with a single injection of the leptin gene.

Scientists working with terminally ill rodents with type 1 diabetes found that they can restore the rodents to full health with a single injection of leptin. They suggest that insulin isn’t the only agent that effectively lowers glucose levels and that leptin could do the same job and for longer periods of time.


The research team thinks that leptin combats diabetes not only by suppressing glucagon’s action on the liver but also by boosting the insulin-like actions of IGF-1 (insulin-like growth factor-1), a hormone that promotes growth and mimics insulin.
 
The investigators tested whether a single injection of the leptin gene given to insulin-deficient mice and rats on the verge of death from diabetic coma could reverse the condition. The researchers tracked the treated rodents for 25 weeks.


The animals that received the leptin gene reportedly began producing excessive amounts of leptin, which countered all the measurable consequences of type 1 diabetes, including weight loss, hyperglycemia, and ketoacidosis.


While the treated animals’ blood glucose levels inched back up over time, their hyperglycemia consistently remained well below the elevated pretreatment levels. The untreated rodents, on the other hand, died within two or three days.


The next step, according to Roger Unger, M.D., professor of internal medicine at UT Southwestern Medical Center and senior author of the article, is to study other potential glucagon suppressants and begin leptin clinical trials within the next year.


Dr. Unger notes that it’s premature to say that leptin may someday replace insulin as a treatment for diabetic patients. He points out that this study does demonstrate that leptin could at least handle some of insulin’s job requirements and do it for longer periods of time. Injected insulin is biologically active for only three to four hours.


“My hope is that you could give leptin for one type of action – glucagon’s suppression, for example – and insulin for another. Or perhaps give a substance other than insulin entirely,” says Dr. Unger.


The findings appear online and will be published in a future issue of the Proceedings of the National Academy of Sciences.

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