Leptin, sometimes called the “satiety hormone” because it suppresses eating behavior, has long been known to play a role in preventing the development of diabetes. Unfortunately, its exact mechanism of action has remained unclear. Recent research, however, suggests that leptin signaling in the brain and elsewhere relies heavily on melanocortin receptor signaling. Additional research based on this original finding, has revealed that melanotan-2 (MT-2) may have the potential to circumvent leptin signaling and directly stimulate melanocortin receptors to fight obesity and prevent the onset of diabetes.
Leptin and Melanotan-2 Signaling Pathway
Leptin and melanotan-2 have effects in the GI system (stomach and intestines) as well as in the brain. It is the effects on the brain that determine satiety and mediate glucose uptake in peripheral tissues. The normal action of leptin on the brain is to increase glucose uptake in skeletal muscle tissue, brown adipose tissue (BAT), and the heart. It also suppresses glucagon production, a hormone that normally raises blood sugar levels. These effects directly reduce blood sugar and thus impacts an individual’s risk of developing diabetes.
Previous research has also indicated that leptin infusion cannot override uncontrolled diabetes or prevent the development of diabetes in animal models. Even though leptin plays a role in modifying peripheral glucose uptake, it does not seem to be potent enough to produce effects in rats that are already diabetic or that are becoming diabetic. At least part of the failed response of leptin in diabetic rats appears to be due to changes in how the hormone crosses from the blood into the brain where it has its effects.
Research from 2009, studying the link between leptin and melanocortin, found that the effects of leptin are mediated by melanocortin. In particular, melanotan-2 produces some of the same actions as leptin, particularly with regard to glucagon suppression1. As an added bonus, melanotan-2 seems to have an easier time crossing from the blood to the brain, suggesting that it may be more potent than leptin as a diabetes treatment. The benefits do not end there, however. Checkout latest information at http://www.renalandurologynews.com/secondary-hyperparathyroidism/leptin-a-potential-target-to-reduce-cvd-risk-in-ckd-mbd/article/525643/
Melanotan-2 research shows Diabetes Fighting Properties
Two of the primary problems of diabetes involve hypersecretion of glucagon into the blood stream (hyperglucogonemia) and the formation of ketone bodies (a process called ketosis). Glucagon has the opposite effects of insulin, acting to raise blood sugar levels and pushing the body toward ketosis.
Research into the effects of melanotan-2 on mice with uncontrolled diabetes have revealed that melanocortin receptors likely play a strong role in preventing the formation of ketone bodies by suppressing glucagon secretion. This may have important consequences for two reasons. First, these findings indicate that melanotan-2 or a derivative may play a role in the treatment of diabetic ketoacidosis in the future. Diabetic ketoacidosis is a serious condition, mediated by glucagon secretion, that requires treatment in an intensive care unit2.
The second reason that these findings are critical is that glucagon is now recognized as a key factor in the development of diabetes. In the past, diabetes was thought to result primarily from insulin dysregulation, but it is now known that insulin administration does not cure diabetes or allow for glucose homeostasis to be achieved. New research shows that beta cell (the cells that produce insulin) destruction does not lead to diabetes in mouse models, further confirming the suspicion that insulin deficiency alone is not enough to cause diabetes. In fact, glucagon overabundance is necessary for diabetes to develop. Treating diabetes via glucagon suppression can actually normalize glucose levels and HBA1c (a measure of long-term blood sugar levels) while improving insulin sensitivity and glucose tolerance3. In other words, our focus on insulin may be misguided. A shift to focusing on glucagon may yield better results.
These research findings suggest that the use of melanotan-2 in conjunction with insulin may one day serve as a means of preventing some of the complications of diabetes by allowing for better control of the disease. More importantly, these findings suggest that it may be possible to ward off diabetes, particularly type II diabetes, through the use of melanotan-2 or other melanocortin receptor agonists.
This peptide is still undergoing scientific research and is not yet approved for human use by the FDA.
3. Lee, Y. H., Wang, M.-Y., Yu, X.-X. & Unger, R. H. Glucagon is the key factor in the development of diabetes. Diabetologia 59, 1372–1375 (2016).