Effect of resveratrol on SNARE proteins expression and insulin resistance in skeletal muscle of diabetic rats

Document Type : Original Article

Authors

1 Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

2 Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

3 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

4 Department of Molecular Medicine and Genetics, Medical School, Hamadan University of Medical Sciences, Hamadan, Iran

5 Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

6 Department of Clinical Biochemistry, Facultyl of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Objective(s): Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex proteins are involved in membrane trafficking. The expression of isoforms of SNAP-23, syntaxin-4, and VAMP-2 is significantly done in skeletal muscles; they control GLUT4 trafficking. It is believed that type 2 diabetes could be caused by the modifications in the expression of SNARE complex proteins. The purpose of this study was to evaluate the effect of resveratrol on the expression of these proteins in type 2 diabetes.
Materials and Methods: Forty male Wistar rats were selected. Streptozotocin and nicotinamide were applied for the induction of type 2 diabetes. The animals were divided into five groups. Healthy and diabetic groups were set as control; resveratrol (1, 5, and 10 mg/kg body weight) was applied to treat the three groups of diabetic rats for 30 days. Real-time qRT-PCR was applied to evaluate the expression of SNARE complex proteins.
Results: There is a link between diabetes and insulin resistance and up-regulation of SNARE proteins expression. Resveratrol improved hyperglycemia and insulin resistance along with a non-significant reduction in the expression of SNARE proteins.
Conclusion: Increased expression of SNARE proteins was possibly a compensatory mechanism in response to insulin resistance in the skeletal muscles of diabetic rats. Resveratrol non-significantly reduced the expression of SNARE proteins by enhancing insulin sensitivity, where this effect was dose-dependent. Thus, higher doses of resveratrol and longer intervention periods could probably be more effective. Another molecular mechanism of the anti-diabetic properties of resveratrol was identified with an effect on the expression of SNARE proteins.

Keywords


1. Hameed I, Masoodi SR, Mir SA, Nabi M, Ghazanfar K, Ganai BA. Type 2 diabetes mellitus: from a metabolic disorder to an inflammatory condition. World J Diabetes 2015; 6: 598-612.
2. Huang S, Czech MP. The GLUT4 glucose transporter. Cell Metab 2007; 5: 237-252.
3. Rea S, James DE. Moving GLUT4: the biogenesis and trafficking of GLUT4 storage vesicles. Diabetes 1997; 46: 1667-1677.
4. Stöckli J, Fazakerley DJ, James DE. GLUT4 exocytosis. J Cell Sci 2011; 124: 4147-4159.
5. Duman JG, Forte JG. What is the role of SNARE proteins in membrane fusion? Am J Physiol Cell Physiol 2003; 285: C237-C249.
6. Foster LJ, Klip A. Mechanism and regulation of GLUT-4 vesicle fusion in muscle and fat cells. Am J Physiol Cell Physiol 2000; 279: C877-C890.
7. Wang T, Li L, Hong W. SNARE proteins in membrane trafficking. Traffic 2017;18:767-775.
8. Pessin JE, Thurmond DC, Elmendorf JS, Coker KJ, Okada S. Molecular basis of insulin-stimulated GLUT4 vesicle trafficking Location! Location! Location! J Biol Chem 1999; 274: 2593-2596.
9. Chamberlain LH, Gould GW. The vesicle-and target-SNARE proteins that mediate Glut4 vesicle fusion are localized in detergent-insoluble lipid rafts present on distinct intracellular membranes. J Biol Chem 2002; 277: 49750-49754.
10. Garvey WT, Maianu L, Zhu JH, Brechtel-Hook G, Wallace P, Baron AD. Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. J Clin Invest 1998; 101: 2377-2386.
11. Chan CB, MacPhail RM, Sheu L, Wheeler MB, Gaisano HY. Beta-cell hypertrophy in fa/fa rats is associated with basal glucose hypersensitivity and reduced SNARE protein expression. Diabetes 1999; 48: 997-1005.
12. Maier VH, Melvin DR, Lister CA, Chapman H, Gould GW, Murphy GJ. v-and t-SNARE protein expression in models of insulin resistance: normalization of glycemia by rosiglitazone treatment corrects overexpression of cellubrevin, vesicle-associated membrane protein-2, and syntaxin 4 in skeletal muscle of Zucker diabetic fatty rats. Diabetes 2000; 49: 618-625.
13. Abbasi Oshaghi E, Goodarzi MT, Higgins V, Adeli K. Role of resveratrol in the management of insulin resistance and related conditions: mechanism of action. Crit Rev Clin Lab Sci 2017; 54: 267-293.
14. Burgess TA, Robich MP, Chu LM, Bianchi C, Sellke FW. Improving glucose metabolism with resveratrol in a swine model of metabolic syndrome through alteration of signaling pathways in the liver and skeletal muscle. Arch Surg 2011; 146: 556-564.
15. Szkudelski T, Szkudelska K. Resveratrol and diabetes: from animal to human studies. Biochim Biophys Acta Mol Basis Dis 2015; 1852: 1145-1154.
16. Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, et al. Resveratrol enhances GLUT‐4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. J Cell Mol Med 2008; 12: 2350-2361.
17. Szkudelska K, Szkudelski T. Resveratrol, obesity and diabetes. Eur J Pharmacol 2010; 635: 1-8.
18. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998; 47: 224-229.
19. Sheela N, Jose MA, Sathyamurthy D, Kumar BN. Effect of silymarin on streptozotocin-nicotinamide-induced type 2 diabetic nephropathy in rats. Iran J Kidney Dis 2013; 7: 117-123.
20. Hasanvand A, Amini-Khoei H, Hadian MR, Abdollahi A, Tavangar SM, Dehpour AR, et al . Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy. Inflammopharmacology 2016; 24:207-219.
21. Su H-C, Hung L-M, Chen J-K. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 2006; 290: E1339-E1346.
22. Kohn DF, Wixson SK, White WJ, Benson GJ, editors. Anesthesia and analgesia in laboratory animals: Elsevier; 1997.
23. Rio DC, Ares M, Hannon GJ, Nilsen TW. Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb Protoc 2010; 2010: pdb. prot5439.
24. Bas A, Forsberg G, Hammarström S, Hammarström ML. Utility of the housekeeping genes 18S rRNA, β‐actin and glyceraldehyde‐3‐phosphate‐dehydrogenase for normalization in real‐time quantitative reverse transcriptase‐polymerase chain reaction analysis of gene expression in human T lymphocytes. Scand J Immunol 2004; 59: 566-573.
25. Katsuki A, Sumida Y, Gabazza EC, Murashima S, Furuta M, Araki-Sasaki R, et al. Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes care 2001; 24: 362-365.
26. Williams D, Pessin JE. Mapping of R-SNARE function at distinct intracellular GLUT4 trafficking steps in adipocytes. J Cell Biol 2008; 180: 375-387.
27. Cheatham B. GLUT4 and company: SNAREing roles in insulin-regulated glucose uptake. Trends Endocrinol Metab 2000; 11: 356-361.
28. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res 2007; 125: 451-472.
29. Chi TC, Chen WP, Chi TL, Kuo TF, Lee SS, Cheng JT, et al. Phosphatidylinositol-3-kinase is involved in the antihyperglycemic effect induced by resveratrol in streptozotocin-induced diabetic rats. Life Sci 2007; 80: 1713-1720.
30. Hambrock A, de Oliveira Franz CB, Hiller S, Grenz A, Ackermann S, Schulze DU, et al. Resveratrol binds to the sulfonylurea receptor (SUR) and induces apoptosis in a SUR subtype-specific manner. J Biol Chem 2007; 282: 3347-3356.
31. Boden MJ, Brandon AE, Tid-Ang JD, Preston E, Wilks D, Stuart E, et al. Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle. Am J Physiol Endocrinol Metab 2012; 303: E798.
32. Östenson CG, Khan A, Abdel-Halim SM, Guenifi A, Suzuki K, Goto Y, et al. Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat. Diabetologia 1993; 36: 3-8.
33. Boström P, Andersson L, Vind B, Håversen L, Rutberg M, Wickström Y, et al. The SNARE protein SNAP23 and the SNARE-interacting protein Munc18c in human skeletal muscle are implicated in insulin resistance/type 2 diabetes. Diabetes 2017; 66:1426.
34. Schlaepfer IR, Pulawa LK, Ferreira LD, James DE, Capell WH, Eckel RH. Increased expression of the SNARE accessory protein Munc18c in lipid-mediated insulin resistance. J Lipid Res 2003; 44: 1174-1181.
35. Greenbaum CJ, Kahn SE, Palmer JP. Nicotinamide’s effects on glucose metabolism in subjects at risk for IDDM. Diabetes 1996; 45: 1631-1634.
36. Farimani AR, Saidijam M, Goodarzi MT, Azari RY, Asadi S, Zarei S, et al. Effect of resveratrol supplementation on the SNARE proteins expression in adipose tissue of stroptozotocin-nicotinamide induced type 2 diabetic rats. Iran J Med Sci 2015; 40: 248-255.
37. Asadi S, Goodarzi MT, Saidijam M, Karimi J, Azari RY, Farimani AR, et al. Resveratrol attenuates visfatin and vaspin genes expression in adipose tissue of rats with type 2 diabetes. Iran J Basic Med Sci 2015; 18: 537-543.
38.  Zarei S, Saidijam M, Karimi J, Yadegarazari R, Farimani AR, Hosseini-Zijood SM, et al. Effect of resveratrol on resistin and apelin gene expressions in adipose tissue of diabetic rats. Turk J Med Sci 2016; 46: 1561-1567.