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Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.

Wang S, Zhai X, Li S, McCabe MF, Wang X, Rong P - PLoS ONE (2015)

Bottom Line: We found that naïve ZDF rats develop hyperglycemia naturally with age.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.We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Xinxiang Medical University, Xinxiang, Henan Province, China; Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China; MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Guangdong Landau Biotechnology Inc. Ltd., Guangzhou, Guangdong, China.

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 30 min 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.

No MeSH data available.


Related in: MedlinePlus

Schematic depiction of the modulation of glucose metabolism following taVNS in T2D.See Discussion for interpretation.
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pone.0124195.g004: Schematic depiction of the modulation of glucose metabolism following taVNS in T2D.See Discussion for interpretation.

Mentions: A theoretic cascade in T2D following taVNS is shown in Fig 4. Briefly, (i) taVNS stimulates the auricular vagal branches, increases the parasympathetic tone, and triggers initial melatonin releases; (ii) melatonin activates α-cells to release glucagon and thus elevates glycemic level; (iii) the released glucagon and the elevated glucose level trigger an instant insulin release from β-cells to reduce the glycemic level and simultaneously inhibit glucagon release; meanwhile, melatonin combines with MT2 receptors on β-cells and inhibits insulin production, thus a delayed but sustained insulin release follows the initial surge; (iv) at a low enough point, the glucose concentration activates epinephrine secretion to trigger melatonin production [34] thus another circle begins. Considering the half-lives of around 10–15 min for insulin [35] and 20 min for melatonin [36], the delayed reaction time of β-cells upon MT2 activation, and the response time of blood glucose, each cycle may take hours.


Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.

Wang S, Zhai X, Li S, McCabe MF, Wang X, Rong P - PLoS ONE (2015)

Schematic depiction of the modulation of glucose metabolism following taVNS in T2D.See Discussion for interpretation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400163&req=5

pone.0124195.g004: Schematic depiction of the modulation of glucose metabolism following taVNS in T2D.See Discussion for interpretation.
Mentions: A theoretic cascade in T2D following taVNS is shown in Fig 4. Briefly, (i) taVNS stimulates the auricular vagal branches, increases the parasympathetic tone, and triggers initial melatonin releases; (ii) melatonin activates α-cells to release glucagon and thus elevates glycemic level; (iii) the released glucagon and the elevated glucose level trigger an instant insulin release from β-cells to reduce the glycemic level and simultaneously inhibit glucagon release; meanwhile, melatonin combines with MT2 receptors on β-cells and inhibits insulin production, thus a delayed but sustained insulin release follows the initial surge; (iv) at a low enough point, the glucose concentration activates epinephrine secretion to trigger melatonin production [34] thus another circle begins. Considering the half-lives of around 10–15 min for insulin [35] and 20 min for melatonin [36], the delayed reaction time of β-cells upon MT2 activation, and the response time of blood glucose, each cycle may take hours.

Bottom Line: We found that naïve ZDF rats develop hyperglycemia naturally with age.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.We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Xinxiang Medical University, Xinxiang, Henan Province, China; Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China; MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Guangdong Landau Biotechnology Inc. Ltd., Guangzhou, Guangdong, China.

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 30 min 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.

No MeSH data available.


Related in: MedlinePlus