Low-Frequency Electroacupuncture Improves Insulin Sensitivity in Obese Diabetic Mice Through Activation of SIRT1/PGC-1α in Skeletal Muscle

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2010 Oct 29

PMID 20981161

Citations 29

Authors

Fengxia Liang

Rui Chen

Atsushi Nakagawa

Makoto Nishizawa

Shinichi Tsuda

Hua Wang

Daisuke Koya

Affiliations

Soon will be listed here.

Abstract

Electroacupuncture (EA) has been observed to reduce insulin resistance in obesity and diabetes. However, the biochemical mechanism underlying this effect remains unclear. This study investigated the effects of low-frequency EA on metabolic action in genetically obese and type 2 diabetic db/db mice. Nine-week-old db/m and db/db mice were randomly divided into four groups, namely, db/m, db/m + EA, db/db, and db/db + EA. db/m + EA and db/db + EA mice received 3-Hz electroacupuncture five times weekly for eight consecutive weeks. In db/db mice, EA tempered the increase in fasting blood glucose, food intake, and body mass and maintained insulin levels. In EA-treated db/db mice, improved insulin sensitivity was established through intraperitoneal insulin tolerance test. EA was likewise observed to decrease free fatty acid levels in db/db mice; it increased protein expression in skeletal muscle Sirtuin 1 (SIRT1) and induced gene expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and acyl-CoA oxidase (ACOX). These results indicated that EA offers a beneficial effect on insulin resistance in obese and diabetic db/db mice, at least partly, via stimulation of SIRT1/PGC-1α, thus resulting in improved insulin signal.

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References

Milne J, Lambert P, Schenk S, Carney D, Smith J, Gagne D . Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007; 450(7170):712-6. PMC: 2753457. DOI: 10.1038/nature06261. View

Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F . Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006; 127(6):1109-22. DOI: 10.1016/j.cell.2006.11.013. View

Chang S, Lin J, CHI T, Liu I, Cheng J . An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats. Diabetologia. 1999; 42(2):250-5. DOI: 10.1007/s001250051146. View

Stener-Victorin E, Jedel E, Janson P, Sverrisdottir Y . Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Regul Integr Comp Physiol. 2009; 297(2):R387-95. DOI: 10.1152/ajpregu.00197.2009. View

Kelly T, Yang W, Chen C, Reynolds K, He J . Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008; 32(9):1431-7. DOI: 10.1038/ijo.2008.102. View

Sugimachi M, Kawada T, Kamiya A, Li M, Zheng C, Sunagawa K . Electrical acupuncture modifies autonomic balance by resetting the neural arc of arterial baroreflex system. Annu Int Conf IEEE Eng Med Biol Soc. 2007; 2007:5334-7. DOI: 10.1109/IEMBS.2007.4353546. View

Pagel-Langenickel I, Bao J, Joseph J, Schwartz D, Mantell B, Xu X . PGC-1alpha integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle. J Biol Chem. 2008; 283(33):22464-72. PMC: 2504883. DOI: 10.1074/jbc.M800842200. View

Puigserver P, Rhee J, Lin J, Wu Z, Yoon J, Zhang C . Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell. 2001; 8(5):971-82. DOI: 10.1016/s1097-2765(01)00390-2. View

Ishizaki N, Okushi N, Yano T, Yamamura Y . Improvement in glucose tolerance as a result of enhanced insulin sensitivity during electroacupuncture in spontaneously diabetic Goto-Kakizaki rats. Metabolism. 2009; 58(10):1372-8. DOI: 10.1016/j.metabol.2009.05.001. View

10.

Greenfield J, Campbell L . Role of the autonomic nervous system and neuropeptides in the development of obesity in humans: targets for therapy?. Curr Pharm Des. 2008; 14(18):1815-20. DOI: 10.2174/138161208784746716. View

11.

Turner N, Bruce C, Beale S, Hoehn K, So T, Rolph M . Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes. 2007; 56(8):2085-92. DOI: 10.2337/db07-0093. View

12.

Liang F, Kume S, Koya D . SIRT1 and insulin resistance. Nat Rev Endocrinol. 2009; 5(7):367-73. DOI: 10.1038/nrendo.2009.101. View

13.

Lin T, Fu T, Chen C, Lin Y, Chien C . Low and high frequency electroacupuncture at Hoku elicits a distinct mechanism to activate sympathetic nervous system in anesthetized rats. Neurosci Lett. 1998; 247(2-3):155-8. DOI: 10.1016/s0304-3940(98)00298-5. View

14.

Fulco M, Sartorelli V . Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues. Cell Cycle. 2008; 7(23):3669-79. PMC: 2607479. DOI: 10.4161/cc.7.23.7164. View

15.

Lee Y, Li T, Tzeng C, Chen Y, Ho W, Lin J . Electroacupuncture at the Zusanli (ST-36) Acupoint Induces a Hypoglycemic Effect by Stimulating the Cholinergic Nerve in a Rat Model of Streptozotocine-Induced Insulin-Dependent Diabetes Mellitus. Evid Based Complement Alternat Med. 2011; 2011:650263. PMC: 3136799. DOI: 10.1093/ecam/neq068. View

16.

Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X . SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007; 6(4):307-19. DOI: 10.1016/j.cmet.2007.08.014. View

17.

Heilbronn L, Gan S, Turner N, Campbell L, Chisholm D . Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects. J Clin Endocrinol Metab. 2007; 92(4):1467-73. DOI: 10.1210/jc.2006-2210. View

18.

Ikarashi N, Toda T, Okaniwa T, Ito K, Ochiai W, Sugiyama K . Anti-Obesity and Anti-Diabetic Effects of Acacia Polyphenol in Obese Diabetic KKAy Mice Fed High-Fat Diet. Evid Based Complement Alternat Med. 2011; 2011:952031. PMC: 3137845. DOI: 10.1093/ecam/nep241. View

19.

Zhang J . The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation. J Biol Chem. 2007; 282(47):34356-64. DOI: 10.1074/jbc.M706644200. View

20.

Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V . Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999; 98(1):115-24. DOI: 10.1016/S0092-8674(00)80611-X. View