A new study finds strong support for role of melatonin and one of its receptor MTNR1B in the development of Type 2 Diabetes. One of the variants of this receptor which is common in many individuals, was associated with increase in fasting glucose over time and predicted future chances of increased risk for Type 2 Diabetes, as a result of impairment of insulin secretion from pancreatic beta cell function. Notably, this effect was more pronounced with increasing age and increased demands imposed by increased age-related insulin resistance.
How is this possible and can this reduce the efficacy of GLP-1 medications? When melatonin binds to the MTNR1B on pancreatic beta cells, it blocks the activation of incretin hormones, namely, GLP-1 and GIP both of which are the components of success behind brand names such as Tirzepatide and Ozempic. It was also observed that although, glucose leads to activation of pancreatic Beta cells to produce insulin, the addition of melatonin blocked this activation and therefore lead to lack of activation with low levels of insulin. In human where variants of MTNR1B receptors are increased, will naturally lead to reduced insulin secretion via the action of melatonin. Studies do show that the circadian rhythm is off in Type 2 Diabetes leading to increased melatonin secretion. This hormone has been shown to be higher during the day in such individuals when normally during the day, the levels are lower. Hence, elevated levels of melatonin in people with increased MTNR1B receptors on pancreatic beta cells can lead to decreased insulin secretion and therefore elevate fasting blood glucose.
How does this apply in future? Development to blockers of melatonin particularly on beta cells can have an impact on increasing insulin release in response to glucose for prevention of development to Type 2 Diabetes. Individuals who fit the risk profile of having increased MTNR1B receptors for melatonin on Beta cells may be less responsive to GLP-1 medications such as Victoza or Ozempic. Identifying such individuals in the future can provide more tailored approach to obesity treatment.
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