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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

Chronic effects of taVNS in rats.Comparing blood glucose concentrations in naïve and taVNS treated ZDF rats (a, n = 6 each), in pinealectomized ZDF rats (immediately after pinealectomy operation) with or without taVNS treatment (b, n = 5 each), and in naïve, taVNS, and AMEA treated ZL rats (c, n = 4 each). ZL, ZDF, naïve ZL or ZDF rats; taVNS, taVNS treated rats; AMEA, auricular margin electroacupuncture treated rats; Px, pinealectomized rats; Px/VS, taVNS treated pinealectomized rats; Mel, daily melatonin injected rats. Bas, baseline (before taVNS); W1–W5, 1–5 weeks after consecutive taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. Bas of the same group; #,##,### P<0.05, 0.01, 0.001 vs. naïve at the same time point, respectively. Concentrations of plasma HbA1c (d, e) and insulin (f, g) upon sampling were compared in naïve ZDF and ZL rats (d, f) and in ZDF rats subjected to different treatments (e, g). *, *** P<0.05, 0.001 vs. ZDF, respectively; ### P<0.001 vs. remaining groups. Sample size estimated based on power level of 0.8.
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pone.0124195.g003: Chronic effects of taVNS in rats.Comparing blood glucose concentrations in naïve and taVNS treated ZDF rats (a, n = 6 each), in pinealectomized ZDF rats (immediately after pinealectomy operation) with or without taVNS treatment (b, n = 5 each), and in naïve, taVNS, and AMEA treated ZL rats (c, n = 4 each). ZL, ZDF, naïve ZL or ZDF rats; taVNS, taVNS treated rats; AMEA, auricular margin electroacupuncture treated rats; Px, pinealectomized rats; Px/VS, taVNS treated pinealectomized rats; Mel, daily melatonin injected rats. Bas, baseline (before taVNS); W1–W5, 1–5 weeks after consecutive taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. Bas of the same group; #,##,### P<0.05, 0.01, 0.001 vs. naïve at the same time point, respectively. Concentrations of plasma HbA1c (d, e) and insulin (f, g) upon sampling were compared in naïve ZDF and ZL rats (d, f) and in ZDF rats subjected to different treatments (e, g). *, *** P<0.05, 0.001 vs. ZDF, respectively; ### P<0.001 vs. remaining groups. Sample size estimated based on power level of 0.8.

Mentions: At 8 weeks of age, the glycemic level in naive ZDF rats was 19.793±7.158 mmol/L (mean ± SD, n = 14; 95% CL, 15.661–23.925). ZDF rats develop hyperglycemia naturally with age but the procession could be broken/reversed by taVNS (Fig 3a). Although each taVNS session produced immediate multiple, fluctuating waves of melatonin, glucagon, and insulin, the wave for blood glucose level shifted downward day by day, such that the glucose concentration was significantly lower on day 5 than that on day 1, both before and 2h after taVNS session, and in both intact and pinealectomized ZDF rats (Fig 2g and 2h).


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)

Chronic effects of taVNS in rats.Comparing blood glucose concentrations in naïve and taVNS treated ZDF rats (a, n = 6 each), in pinealectomized ZDF rats (immediately after pinealectomy operation) with or without taVNS treatment (b, n = 5 each), and in naïve, taVNS, and AMEA treated ZL rats (c, n = 4 each). ZL, ZDF, naïve ZL or ZDF rats; taVNS, taVNS treated rats; AMEA, auricular margin electroacupuncture treated rats; Px, pinealectomized rats; Px/VS, taVNS treated pinealectomized rats; Mel, daily melatonin injected rats. Bas, baseline (before taVNS); W1–W5, 1–5 weeks after consecutive taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. Bas of the same group; #,##,### P<0.05, 0.01, 0.001 vs. naïve at the same time point, respectively. Concentrations of plasma HbA1c (d, e) and insulin (f, g) upon sampling were compared in naïve ZDF and ZL rats (d, f) and in ZDF rats subjected to different treatments (e, g). *, *** P<0.05, 0.001 vs. ZDF, respectively; ### P<0.001 vs. remaining groups. Sample size estimated based on power level of 0.8.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4400163&req=5

pone.0124195.g003: Chronic effects of taVNS in rats.Comparing blood glucose concentrations in naïve and taVNS treated ZDF rats (a, n = 6 each), in pinealectomized ZDF rats (immediately after pinealectomy operation) with or without taVNS treatment (b, n = 5 each), and in naïve, taVNS, and AMEA treated ZL rats (c, n = 4 each). ZL, ZDF, naïve ZL or ZDF rats; taVNS, taVNS treated rats; AMEA, auricular margin electroacupuncture treated rats; Px, pinealectomized rats; Px/VS, taVNS treated pinealectomized rats; Mel, daily melatonin injected rats. Bas, baseline (before taVNS); W1–W5, 1–5 weeks after consecutive taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. Bas of the same group; #,##,### P<0.05, 0.01, 0.001 vs. naïve at the same time point, respectively. Concentrations of plasma HbA1c (d, e) and insulin (f, g) upon sampling were compared in naïve ZDF and ZL rats (d, f) and in ZDF rats subjected to different treatments (e, g). *, *** P<0.05, 0.001 vs. ZDF, respectively; ### P<0.001 vs. remaining groups. Sample size estimated based on power level of 0.8.
Mentions: At 8 weeks of age, the glycemic level in naive ZDF rats was 19.793±7.158 mmol/L (mean ± SD, n = 14; 95% CL, 15.661–23.925). ZDF rats develop hyperglycemia naturally with age but the procession could be broken/reversed by taVNS (Fig 3a). Although each taVNS session produced immediate multiple, fluctuating waves of melatonin, glucagon, and insulin, the wave for blood glucose level shifted downward day by day, such that the glucose concentration was significantly lower on day 5 than that on day 1, both before and 2h after taVNS session, and in both intact and pinealectomized ZDF rats (Fig 2g and 2h).

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