Abstract
Melatonin plays a protective role in type 2 diabetes (T2D) through regulation of glucose metabolism. Whether transcutaneous vagus nerve stimulation (taVNS) is antidiabetic and whether a modulated melatonin production is involved in the antidiabetic mechanism of taVNS is unknown. In this study, once daily 30min noninvasive taVNS was administered in Zucker diabetic fatty (ZDF, fa/fa) and Zucker lean (ZL, +/fa) littermates under anesthesia for 5 consecutive weeks. The acute and chronic influences of taVNS on the secretion of melatonin were studied as well as the effects of taVNS on blood glucose metabolism. We found that naïve ZDF rats develop hyperglycemia naturally with age. Each taVNS session would trigger a tidal secretion of melatonin both during and after the taVNS procedure and induce an acute two-phase glycemic change, a steep increase followed by a gradual decrease. Once daily taVNS sessions eventually reduced the glucose concentration to a normal level in seven days and effectively maintained the normal glycemic and plasma glycosylated hemoglobin (HbAlc) levels when applied for five consecutive weeks. These beneficial effects of taVNS also exist in pinealectomized rats, which otherwise would show overt and continuous hyperglycemia, hyperinsulinemia, and high HbAlc levels. We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin. This finding may have potential importance in developing new approaches to the treatment of T2D, which is highly prevalent, incurable with any current approaches, and very costly to the world.
Highlights
Type 2 diabetes (T2D) is a metabolic disorder characterized by high blood sugar levels due to increased insulin resistance, in which the body’s cells have lost the ability to respond adequately to relatively normal levels of insulin [1]
In this study we found that transcutaneous vagus nerve stimulation (taVNS) triggers melatonin release in a tidal manner and inhibits the progression of T2D
The pineal melatonin is secreted in the night while the extrapineal melatonin secretion, as induced by taVNS, may be different from pineal melatonin secretion
Summary
Type 2 diabetes (T2D) is a metabolic disorder characterized by high blood sugar levels due to increased insulin resistance, in which the body’s cells have lost the ability to respond adequately to relatively normal levels of insulin [1]. The metabolism of blood glucose is mainly and directly regulated by glucagon secreted from pancreatic α-cells in response to low glucose levels and insulin from β-cells to high glucose levels. Insulin secretion is regulated by growth hormone, glucagon like peptide-1, and other hormones and substances [1]. Melatonin (N-acetyl-5-methoxytryptamine) is the hormone that functions as the mediator of photoperiodic information to the central nervous system in vertebrates and allows central circadian regulation of numerous physiological homeostatic mechanisms [3,4,5,6]. It was recently discovered that melatonin plays a protective role against T2D through regulation of glucose metabolism in animals [3,5] and patients [4] via changes in insulin secretion and leptin production [2]
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