Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes

Clinical Science

Volumn 129, Issue 10, 2015, Pages 839-850

  Liu, Tong Yan ^a   Shi, Chang Xiang ^a   Gao, Run ^a   Sun, Hai Jian ^a   Xiong, Xiao Qing ^a   Ding, Lei ^a   Chen, Qi ^a   Li, Yue Hua ^a   Wang, Jue Jin ^a   Kang, Yu Ming ^b   Zhu, Guo Qing ^a  

^a NANJING MEDICAL UNIVERSITY   (China)

^b MEDICAL SCHOOL OF XI AN JIAOTONG UNIVERSITY   (China)

Author keywords

Diabetes; Gluconeogenesis; Glycogenesis; Insulin resistance; Irisin; Liver

Indexed keywords

GLUCOSAMINE; GLUCOSE; GLUCOSE 6 PHOSPHATASE; GLYCOGEN; INSULIN; IRISIN; PALMITIC ACID; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE P110ALPHA; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); PHOSPHOTRANSFERASE; PROTEIN KINASE B; STREPTOZOCIN; TRANSCRIPTION FACTOR FKHR; UNCLASSIFIED DRUG; 2-(4-MORPHOLINYL)-8-PHENYL-4H-1-BENZOPYRAN-4-ONE; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; CHROMONE DERIVATIVE; FIBRONECTIN; FNDC5 PROTEIN, MOUSE; FUSED HETEROCYCLIC RINGS; GLYCOGEN SYNTHASE; MORPHOLINE DERIVATIVE; PHOSPHOENOLPYRUVATE CARBOXYKINASE (ATP); PIK3CA PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DIET RESTRICTION; DRUG EFFICACY; DRUG MECHANISM; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCOGEN ANALYSIS; GLYCOGEN SYNTHESIS; HEPG2 CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; LIVER; LIVER CELL; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PERFUSION; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RECEPTOR DOWN REGULATION; SIGNAL TRANSDUCTION; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; BLOOD; C57BL MOUSE; CELL CULTURE; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; GENETICS; METABOLISM; PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; CELLS, CULTURED; CHROMONES; DIABETES MELLITUS, TYPE 2; FIBRONECTINS; GLUCONEOGENESIS; GLUCOSE; GLUCOSE-6-PHOSPHATASE; GLYCOGEN; GLYCOGEN SYNTHASE; HEP G2 CELLS; HEPATOCYTES; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; INSULIN RESISTANCE; LIVER; MALE; MICE, INBRED C57BL; MORPHOLINES; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHOENOLPYRUVATE CARBOXYKINASE (ATP); PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

EID: 84947339480     PISSN: 01435221     EISSN: 14708736     Source Type: Journal    
DOI: 10.1042/CS20150009     Document Type: Article

References (47)

1. Nordlie, R.C., Foster, J.D. and Lange, A.J. (1999) Regulation of glucose production by the liver. Annu. Rev. Nutr. 19, 379-406
2. Wu, C., Okar, D.A., Kang, J. and Lange, A.J. (2005) Reduction of hepatic glucose production as a therapeutic target in the treatment of diabetes. Curr. Drug Targets Immune Endocr. Metabol. Disord. 5, 51-59
3. Barthel, A. and Schmoll, D. (2003) Novel concepts in insulin regulation of hepatic gluconeogenesis. Am. J. Physiol. Endocrinol. Metab. 285, E685-E692
4. Tsintzas, K., Norton, L., Chokkalingam, K., Nizamani, N., Cooper, S., Stephens, F., Billeter, R. and Bennett, A. (2013) Independent and combined effects of acute physiological hyperglycaemia and hyperinsulinaemia on metabolic gene expression in human skeletal muscle. Clin. Sci. (Lond.) 124, 675-684
5. Yoon, J.C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C.R., Granner, D.K. et al. (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413, 131-138
6. Biddinger, S.B. and Kahn, C.R. (2006) From mice to men: insights into the insulin resistance syndromes. Annu. Rev. Physiol. 68, 123-158
7. Bostrom, P., Wu, J., Jedrychowski, M.P., Korde, A., Ye, L., Lo, J.C., Rasbach, K.A., Bostrom, E.A., Choi, J.H., Long, J.Z. et al. (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463-468
8. Al-Daghri, N.M., Al-Attas, O.S., Alokail, M.S., Alkharfy, K.M., Yousef, M., Vinodson, B., Amer, O.E., Alnaami, A.M., Sabico, S., Tripathi, G. et al. (2014) Maternal inheritance of circulating irisin in humans. Clin. Sci. (Lond.) 126, 837-844
9. Hojlund, K. and Bostrom, P. (2013) Irisin in obesity and type 2 diabetes. J. Diabetes Complications 27, 303-304
10. Piya, M.K., Harte, A.L., Sivakumar, K., Tripathi, G., Voyias, P.D., James, S., Sabico, S., Al-Daghri, N.M., Saravanan, P., Barber, T.M. et al. (2014) The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes. Am. J. Physiol. Endocrinol. Metab. 306, E512-E518
11. Al-Daghri, N.M., Alkharfy, K.M., Rahman, S., Amer, O.E., Vinodson, B., Sabico, S., Piya, M.K., Harte, A.L., McTernan, P.G., Alokail, M.S. et al. (2014) Irisin as a predictor of glucose metabolism in children: sexually dimorphic effects. Eur. J. Clin. Invest. 44, 119-124
12. Choi, Y.K., Kim, M.K., Bae, K.H., Seo, H.A., Jeong, J.Y., Lee, W.K., Kim, J.G., Lee, I.K. and Park, K.G. (2013) Serum irisin levels in new-onset type 2 diabetes. Diabetes Res. Clin. Pract. 100, 96-101
13. Liu, J.J., Wong, M.D., Toy, W.C., Tan, C.S., Liu, S., Ng, X.W., Tavintharan, S., Sum, C.F. and Lim, S.C. (2013) Lower circulating irisin is associated with type 2 diabetes mellitus. J. Diabetes Complications 27, 365-369
14. Kurdiova, T., Balaz, M., Vician, M., Maderova, D., Vlcek, M., Valkovic, L., Srbecky, M., Imrich, R., Kyselovicova, O., Belan, V. et al. (2014) Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J. Physiol. 592, 1091-1107
15. Zhang, C., Ding, Z., Lv, G., Li, J., Zhou, P. and Zhang, J. (2015) Lower irisin level in patients with type 2 diabetes mellitus: a case-control study and meta-analysis. J. Diabetes
16. Aydin, S., Kuloglu, T., Aydin, S., Eren, M.N., Celik, A., Yilmaz, M., Kalayci, M., Sahin, I., Gungor, O., Gurel, A. et al. (2014) Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle. Peptides 52, 68-73
17. Zhang, H.J., Zhang, X.F., Ma, Z.M., Pan, L.L., Chen, Z., Han, H.W., Han, C.K., Zhuang, X.J., Lu, Y., Li, X.J. et al. (2013) Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J. Hepatol. 59, 557-562
18. Basu, R., Chandramouli, V., Dicke, B., Landau, B. and Rizza, R. (2005) Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis. Diabetes 54, 1942-1948
19. Boden, G. (2004) Gluconeogenesis and glycogenolysis in health and diabetes. J. Investig. Med. 52, 375-378
20. Sun, C., Zhang, F., Ge, X., Yan, T., Chen, X., Shi, X. and Zhai, Q. (2007) SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 6, 307-319
21. Gao, D., Nong, S., Huang, X., Lu, Y., Zhao, H., Lin, Y., Man, Y., Wang, S., Yang, J. and Li, J. (2010) The effects of palmitate on hepatic insulin resistance are mediated by NADPH Oxidase 3-derived reactive oxygen species through JNK and p38MAPK pathways. J. Biol. Chem. 285, 29965-29973
22. Lin, Y.Y., Lu, J.Y., Zhang, J., Walter, W., Dang, W., Wan, J., Tao, S.C., Qian, J., Zhao, Y., Boeke, J.D. et al. (2009) Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell 136, 1073-1084
23. Favaro, E., Bensaad, K., Chong, M.G., Tennant, D.A., Ferguson, D.J., Snell, C., Steers, G., Turley, H., Li, J.L., Gunther, U.L. et al. (2012) Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells. Cell Metab. 16, 751-764
24. Perez-Mendoza, M., Rivera-Zavala, J.B. and Díaz-Munoz, M. (2014) Daytime restricted feeding modifies the daily variations of liver gluconeogenesis: adaptations in biochemical and endocrine regulators. Chronobiol. Int. 31, 815-828
25. Reed, M.J., Meszaros, K., Entes, L.J., Claypool, M.D., Pinkett, J.G., Gadbois, T.M. and Reaven, G.M. (2000) A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 49, 1390-1394
26. Zhang, M., Lv, X.Y., Li, J., Xu, Z.G. and Chen, L. (2008) The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp. Diabetes Res. 2008, 704045
27. Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C.L. and Ramarao, P. (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol. Res. 52, 313-320
28. Aydin, S., Ogeturk, M., Kuloglu, T., Kavakli, A. and Aydin, S. (2015) Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation. Peptides 64, 14-23
29. Miyamoto-Mikami, E., Sato, K., Kurihara, T., Hasegawa, N., Fujie, S., Fujita, S., Sanada, K., Hamaoka, T., Tabata, I. and Iemitsu, M. (2015) Endurance training-induced increase in circulating irisin levels is associated with reduction of abdominal visceral fat in middle-aged and older adults. PLoS ONE 10, e0120354
30. Mansuy-Aubert, V., Zhou, Q.L., Xie, X., Gong, Z., Huang, J.Y., Khan, A.R., Aubert, G., Candelaria, K., Thomas, S., Shin, D.J. et al. (2013) Imbalance between neutrophil elastase and its inhibitor alpha1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 17, 534-548
31. Lee, J. and Kim, M.S. (2007) The role of GSK3 in glucose homeostasis and the development of insulin resistance. Diabetes Res. Clin. Pract. 77 (Suppl. 1), S49-S57
32. Cohen, P. and Frame, S. (2001) The renaissance of GSK3. Nat. Rev. Mol. Cell Biol. 2, 769-776
33. Hawkins, P. T., Anderson, K.E., Davidson, K. and Stephens, L.R. (2006) Signalling through class I PI3Ks in mammalian cells. Biochem. Soc. Trans. 34, 647-662
34. Cheng, Z. and White, M.F. (2011) Targeting Forkhead box O1 from the concept to metabolic diseases: lessons from mouse models. Antioxid. Redox Signal. 14, 649-661
35. Kousteni, S. (2012) FoxO1, the transcriptional chief of staffof energy metabolism. Bone 50, 437-443
36. Barthel, A. and Schmoll, D. (2003) Novel concepts in insulin regulation of hepatic gluconeogenesis. Am. J. Physiol. Endocrinol. Metab. 285, E685-E692
37. Henriksen, E.J. and Dokken, B.B. (2006) Role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Curr. Drug Targets 7, 1435-1441
38. Lee, J. and Kim, M.S. (2007) The role of GSK3 in glucose homeostasis and the development of insulin resistance. Diabetes Res. Clin. Pract. 77 (Suppl. 1), S49-S57
39. Nakae, J., Biggs, W.H., III, Kitamura, T., Cavenee, W.K., Wright, C.V., Arden, K.C. and Accili, D. (2002) Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat. Genet. 32, 245-253
40. Wang, Q., Wang, N., Dong, M., Chen, F., Li, Z. and Chen, Y. (2014) GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice. Clin. Sci. (Lond.) 127, 91-100
41. MacAulay, K. and Woodgett, J.R. (2008) Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of Type 2 diabetes. Expert Opin. Ther. Targets 12, 1265-1274
42. Perry, R.J., Samuel, V.T., Petersen, K.F. and Shulman, G.I. (2014) The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510, 84-91
43. Liu, J.J., Wong, M.D., Toy, W.C., Tan, C.S., Liu, S., Ng, X.W., Tavintharan, S., Sum, C.F. and Lim, S.C. (2013) Lower circulating irisin is associated with type 2 diabetes mellitus. J. Diabetes Complications 27, 365-369
44. Huh, J.Y., Panagiotou, G., Mougios, V., Brinkoetter, M., Vamvini, M.T., Schneider, B.E. and Mantzoros, C.S. (2012) FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 61, 1725-1738
45. Stengel, A., Hofmann, T., Goebel-Stengel, M., Elbelt, U., Kobelt, P. and Klapp, B.F. (2013) Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity-Correlation with body mass index. Peptides 39, 125-130
46. Hojlund, K. and Bostrom, P. (2013) Irisin in obesity and type 2 diabetes. J. Diabetes Complications 27, 303-304
47. Albrecht, E., Norheim, F., Thiede, B., Holen, T., Ohashi, T., Schering, L., Lee, S., Brenmoehl, J., Thomas, S., Drevon, C.A. et al. (2015) Irisin-a myth rather than an exercise-inducible myokine. Sci. Rep. 5, 8889