Leptin activates a brain mechanism that may be able to keep diabetics alive without insulin, according to a study published Tuesday in Cell Metabolism. The study can be found at this link when it is placed online.
If the findings in mice are confirmed, the research has solved a problem preventing wider use of leptin, a hormone known for its slimming effects. Efforts to develop leptin as a drug have failed because human trials failed to replicate animal findings.
The paper calls the idea that life requires insulin a "dogma," that is being refuted.
Leptin activates neurons in the hypothalamus that regulate blood glucose, the study found. Earlier studies by the researchers and others have found that rodents can survive without insulin if given leptin. However, the mechanism of action wasn't known. With knowledge of the pathway used by leptin, researchers can now look for ways to apply it to people, the paper stated.
The study's first author is Teppei Fujikawa of the University of Texas Southwestern Medical Center in Dallas. The senior author is Roberto Coppari of the medical center, University of California, Irvine and the University of Geneva in Geneva, Switzerland.
A second pathway other than insulin for lowering blood sugar would increase treatment options for insulin-dependent diabetics. An advantage of leptin therapy in the rodents is that it lowered blood glucose without producing hypoglycemia, the study found. Moreover, it caused fat to be burned.
The researchers also found which tissues are affected by leptin when insulin is absent. They are in the liver, the soleus muscle in the calf, and brown fat.
The study went to great lengths to ensure that its mice had no insulin at all. Earlier trials of insulin-free mice used animals injected with a chemical that kills the insulin-producing islet cells. However, the mice still make a minute amount of insulin, which might have been required for the leptin to work. So researchers used mice genetically engineered so they can be made virtually incapable of making any insulin at all.
Control mice died within 15 days of being treated to lack insulin. But when the insulin-lacking mice were given leptin, they became viable, and showed more normal levels of blood sugar.
"Collectively, our data elucidate a hypothalamic-dependent pathway enabling life without insulin and hence pave the way for developing better treatments for diseases of insulin deficiency," the study stated.