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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

Acute effects of taVNS in ZDF rats.Comparison between naïve ZDF rats (left column, n = 5) and pinealectomized ZDF rats (two weeks after pinealectomy operation) (right column, n = 5), as well as among day 1, 3, and 5 of the consecutive once-daily-30min-taVNS treatment (shadow area), changes in plasma concentration of melatonin (a, b), glucagon (c, d), and insulin (e, f), and blood glucose levels (g, h). 0.0–3.0, elapsed time in hour beginning from the start of the taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. baseline (0.0) of the same day; #, ### P<0.05, 0.001 vs. day 1 at the same abscissa point, respectively. Sample size estimated based on power level of 0.8.
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pone.0124195.g002: Acute effects of taVNS in ZDF rats.Comparison between naïve ZDF rats (left column, n = 5) and pinealectomized ZDF rats (two weeks after pinealectomy operation) (right column, n = 5), as well as among day 1, 3, and 5 of the consecutive once-daily-30min-taVNS treatment (shadow area), changes in plasma concentration of melatonin (a, b), glucagon (c, d), and insulin (e, f), and blood glucose levels (g, h). 0.0–3.0, elapsed time in hour beginning from the start of the taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. baseline (0.0) of the same day; #, ### P<0.05, 0.001 vs. day 1 at the same abscissa point, respectively. Sample size estimated based on power level of 0.8.

Mentions: As detected from samples taken on day 1, 3, and 5, each taVNS session would induce tidal melatonin release with multiple parabolic waves. The waves existed both during and after the taVNS session (Fig 2a). A comparison between the during- and after-taVNS waves shows the latter as having a longer period and lower frequency, while retaining amplitude. As compared between days, the melatonin waves tend to be higher or more frequent as the rats participated in more sessions (Fig 2a and 2b). The taVNS triggered acute, tidal, and rhythmic melatonin secretions existed in intact (Fig 2a) as well as in pinealectomized ZDF rats (Fig 2b), indicating that taVNS triggers extrapineal melatonin secretion.


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)

Acute effects of taVNS in ZDF rats.Comparison between naïve ZDF rats (left column, n = 5) and pinealectomized ZDF rats (two weeks after pinealectomy operation) (right column, n = 5), as well as among day 1, 3, and 5 of the consecutive once-daily-30min-taVNS treatment (shadow area), changes in plasma concentration of melatonin (a, b), glucagon (c, d), and insulin (e, f), and blood glucose levels (g, h). 0.0–3.0, elapsed time in hour beginning from the start of the taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. baseline (0.0) of the same day; #, ### P<0.05, 0.001 vs. day 1 at the same abscissa point, respectively. Sample size estimated based on power level of 0.8.
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Related In: Results  -  Collection

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

pone.0124195.g002: Acute effects of taVNS in ZDF rats.Comparison between naïve ZDF rats (left column, n = 5) and pinealectomized ZDF rats (two weeks after pinealectomy operation) (right column, n = 5), as well as among day 1, 3, and 5 of the consecutive once-daily-30min-taVNS treatment (shadow area), changes in plasma concentration of melatonin (a, b), glucagon (c, d), and insulin (e, f), and blood glucose levels (g, h). 0.0–3.0, elapsed time in hour beginning from the start of the taVNS treatment. *, **, *** P<0.05, 0.01, 0.001 vs. baseline (0.0) of the same day; #, ### P<0.05, 0.001 vs. day 1 at the same abscissa point, respectively. Sample size estimated based on power level of 0.8.
Mentions: As detected from samples taken on day 1, 3, and 5, each taVNS session would induce tidal melatonin release with multiple parabolic waves. The waves existed both during and after the taVNS session (Fig 2a). A comparison between the during- and after-taVNS waves shows the latter as having a longer period and lower frequency, while retaining amplitude. As compared between days, the melatonin waves tend to be higher or more frequent as the rats participated in more sessions (Fig 2a and 2b). The taVNS triggered acute, tidal, and rhythmic melatonin secretions existed in intact (Fig 2a) as well as in pinealectomized ZDF rats (Fig 2b), indicating that taVNS triggers extrapineal melatonin secretion.

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