Leptin Resurrected: Leptin Therapy in Type I Diabetes

An online science news item jumped out at me the other day, news about leptin and it’s potential use in type I diabetes. While leptin was certainly familiar, it’s recollection brought vague feelings of disappointment. Wasn’t leptin the naturally occurring fat burning compound that was going to make us all thin?

In case you too are wondering what became of leptin, here’s a brief look backward, and then forward, at the leptin story.

Rockefeller University’s Jeffrey Friedman, in 1994, announced the discovery of a protein that controlled appetite. Friedman named the protein “leptin” from the Greek root “leptos”, meaning “thin”. Fat cells secrete leptin, which travels through the bloodstream to the hypothalamus region of the brain. The hypothalamus is the control center for thirst, hunger, sex drive and other hormone-fueled functions. When the body has stored enough fat, the hypothalamus is saturated with leptin, triggering an all-full signal and appetite suppression.

Friedman’s research showed that obese mice lost weight when given leptin. However, in clinical trials, obese humans treated with leptin frequently became resistant to the protein. An excellent review of some of the leptin and obesity work, written by Friedman, was published in Nature, in October of 1998 (1).

Since the mid-90s endocrinologists have worked to understand and overcome leptin resistance and in the past year there’s been exciting news in the leptin-weight loss story (2), but that’s another blog.

You don’t have to have a primary family member with type 1 diabetes to know that this is a very difficult disease to live with. Therapy with injected insulin, while life saving, is a far-cry from the desired “metabolic homeostasis” of insulin produced by a person’s pancreatic islet cells (3). Imagine the body’s multiple insulin requirements; those of the upstream targets like alpha cells and hepatocytes as well as those of the downstream targets like skeletal muscle cells and fat cells (3).

Adequate insulin levels are difficult to regulate by injection and unregulated insulin and blood glucose levels can both have serious, even fatal consequences. But there are more insidious problems for those taking insulin. Insulin is lipogenic, meaning that it can result in increased blood levels of triacylglycerols, LDL and eventually other cardiotoxic lipid compounds. Chronic hyperinsulinemia is suspected of causing cholesterol formation and thus contributes to a relatively high incidence of coronary artery disease in type I diabetics.

As if that weren’t enough, patients with type I diabetes and normal plasma lipid and lipoprotein levels frequently have apoB-lipoproteins that are ester-enriched and potentially more atherogenic (3).

In this recently published study, Wang et al. compared therapeutic actions of insulin and leptin in a nonobese mouse model of T1DM (type I diabetes mellitus). They found that both hormones prevented ketoacidosis (4) (high blood sugar levels resulting in fat breaking down into toxic ketones), cachexia (muscle wasting) and death in a mouse model. And both insulin and leptin restored hemoglobin Alc to normal levels.

However, there were dramatic differences as well. For example, leptin suppressed lipogenesis, while insulin promoted factors involved in lipid, as well as cholesterol formation in the blood stream.

Leptin, either alone or with low-dose insulin therapy, provided equal or better glycemic stability without increased body fat and without increasing enzymes linked to cholesterol and lipid production, problems observed with insulin therapy alone.

The study’s authors thus propose the possibility of a role for the hormone leptin as a supplement in the treatment of human T1DM.

As for an association of leptin with improved health, it seems that things are once again looking up. Leptin, resurrected.

References

  1. Friedman, J. and Halaas, J.L. (1998) Leptin and the regulation of body weight in mammals. Nature 395 763–70. PMID: 9796811
  2. Funato, H. et al. (2009) Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metabolism 9, 64–76. PMID: 19117547
  3. Wang MY, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, Wenner BR, Bain JR, Charron MJ, Newgard CB, & Unger RH (2010). Feature Article: Leptin therapy in insulin-deficient type I diabetes. Proceedings of the National Academy of Sciences of the United States of America PMID: 20194735
  4. Mayo Clinic Online Health Information:Ketoacidosis.
  5. ResearchBlogging.org

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Kari Kenefick

Kari has been a science writer/editor for Promega since 1996. Prior to that she enjoyed working in veterinary microbiology/immunology, and has an M.S. in Bacteriology, U of WI-Madison. Favorite topics include infectious disease, inflammation, aging, exercise, nutrition and personality traits. When not writing, she enjoys training her dogs in agility and obedience. About the practice of writing, as we say in DNA purification, spin, rinse and repeat.

9 thoughts on “Leptin Resurrected: Leptin Therapy in Type I Diabetes

  1. Homeopathy isn’t my area of expertise but our readers may be interested in learning more about it. Thanks for your comment!

  2. It is the common myth that if you suffer from diabetes, you have to eat special food that is often very expensive. In reality the diet works for the best if the food consists of proteins, carbohydrates and fats, but in right combination.

    • Thanks for your comment, Elliot. I agree that diet is a very important focus for diabetics, and that the counsel of a registered dietician should be arranged for those with diabetes.

  3. This is an interesting breakthrough and it certainly looks like Leptin has got a place under controlled measures.

    I can however see that it could be abused by some just wanting to lose weight for vanity reasons so it would be wise to consult a medical professional.

    • Thanks for your comment, Nicola. And I agree, one’s personal physician is the best place to go to learn more about any sort of drug therapy or diet, be it for weight loss or diabetes. I’m a big fan of exercise and good nutrition where weight loss is concerned.

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