Decrease of Hyperglycemia by Syringaldehyde in Diabetic Rats

Abstract

Syringaldehyde is one of the active principles from the stems of Hibiscus taiwanensis (Malvaceae) that has been mentioned to lower hyperglycemia. However, the potential mechanisms for this action of syringaldehyde remain obscure. In the present study, we used streptozotocin to induce diabetic rats (STZ-diabetic rats) as type 1-like diabetic rats and fed fructose-rich chow to rats as type 2-like diabetic rats. Then, we performed the postprandial glucose test and applied the hyperinsulinemic euglycemic clamp to investigate the actions of syringaldehyde. Also, the changes of gene expressions of enzyme relating to glucose homeostasis in muscle and liver were characterized. Syringaldehyde significantly decreased the postprandial plasma glucose in rats, while the plasma insulin was not modified by syringaldehyde. The glucose infusion rate (GIR) in fructose chow-fed rats using hyperinsulinemic euglycemic clamp was markedly improved by syringaldehyde. Additionally, repeated administration of syringaldehyde for 3 days in STZ-diabetic rats resulted in a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Our results suggest that syringaldehyde may increase glucose utilization to lower hyperglycemia in diabetic rats.

Key words

diabetes - glucose infusion rate - hyperinsulinemic euglycemic clamp - postprandial glucose - syringaldehyde

• References

• 1 Jeffcoate SL. Diabetes control and complications: the role of glycated haemoglobin, 25 years on. Diabet Med 2004; 21: 657-665
• 2 Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414: 782-787
• 3 Avitabile NA, Banka A, Fonseca VA. Glucose control and cardiovascular outcomes in individuals with diabetes mellitus: lessons learned from the megatrials. Heart Fail Clin 2012; 8: 513-522
• 4 Jarab AS, Alqudah SG, Mukattash TL, Shattat G, Al-Qirim T. Randomized controlled trial of clinical pharmacy management of patients with type 2 diabetes in an outpatient diabetes clinic in jordan. J Manag Care Pharm 2012; 18: 516-526
• 5 Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012; 5: 313-327
• 6 Lindström J, Louheranta A, Mannelin M, Rastas M, Salminen V, Eriksson J, Uusitupa M, Tuomilehto J. The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity. Diabetes Care 2003; 26: 3230-3236
• 7 Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012; 379: 2243-2251
• 8 El-Sayed MI. Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus patients as adjunctive and alternative therapy. J Ethnopharmacol 2011; 137: 643-651
• 9 Liao Z, Chen X, Wu M. Antidiabetic effect of flavones from Cirsium japonicum DC in diabetic rats. Arch Pharm Res 2010; 33: 353-362
• 10 Lee S, Monnappa AK, Mitchell RJ. Biological activities of lignin hydrolysate-related compounds. BMB Rep 2012; 45: 265-274
• 11 Shen CC, Ni CL, Shen YC, Huang YL, Kuo CH, Wu TS, Chen CC. Phenolic constituents from the stem bark of Magnolia officinalis. J Nat Prod 2009; 72: 168-171
• 12 Michalska K, Kisiel W. The first guaian-12-oic acid glucopyranosyl ester and other constituents from Picris rhagadioloides (L.) Desf. (Asteraceae). Molecules 2008; 13: 444-451
• 13 Guchu E, Diaz-Maroto MC, Diaz-Maroto IJ, Vila-Lameiro P, Perez-Coello MS. Influence of the species and geographical location on volatile composition of Spanish oak wood (Quercus petraea Liebl. and Quercus robur L.). J Agric Food Chem 2006; 54: 3062-3066
• 14 Huang CH, Chen MF, Chung HH, Cheng JT. Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats. J Nat Prod 2012; 75: 1465-1468
• 15 Liu IM, Chang CK, Juang SW, Kou DH, Tong YC, Cheng KC, Cheng JT. Role of hyperglycaemia in the pathogenesis of hypotension observed in type-1 diabetic rats. Int J Exp Pathol 2008; 89: 292-300
• 16 Chen YW, Hsieh PL, Chen YC, Hung CH, Cheng JT. Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats. Anesth Analg 2013; 116: 482-490
• 17 Chiu YJ, Chung HH, Yeh CH, Cheng JT, Lo SH. Improvement of Insulin Resistance by Chlorella in Fructose-rich Chow-fed Rats. Phytother Res 2011; 25: 1306-1312
• 18 Lai DM, Tu YK, Liu IM, Chen PF, Cheng JT. Mediation of beta-endorphin by ginsenoside Rh2 to lower plasma glucose in streptozotocin-induced diabetic rats. Planta Med 2006; 72: 9-13
• 19 Matsuo T, Odaka H, Ikeda H. Effect of an intestinal disaccharidase inhibitor (AO-128) on obesity and diabetes. Am J Clin Nutr 1992; 55 (1 Suppl) 314S-317S
• 20 Kim SH, Jo SH, Kwon YI, Hwang JK. Effects of Onion (Allium cepa L.) Extract Administration on Intestinal alpha-Glucosidases Activities and Spikes in Postprandial Blood Glucose Levels in SD Rats Model. Int J Mol Sci 2011; 12: 3757-3769
• 21 Su CH, Liu IM, Chung HH, Cheng JT. Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats. Neurosci Lett 2009; 457: 125-128
• 22 Steele R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci 1959; 82: 420-430
• 23 Hwang SL, Liu IM, Tzeng TF, Cheng JT. Activation of imidazoline receptors in adrenal gland to lower plasma glucose in streptozotocin-induced diabetic rats. Diabetologia 2005; 48: 767-775
• 24 Luo X, Zhang Y, Ruan X, Jiang X, Zhu L, Wang X, Ding Q, Liu W, Pan Y, Wang Z, Chen Y. Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis. Diabetes 2011; 60: 1435-1445
• 25 Giugliano D, Ceriello A, Esposito K. Glucose metabolism and hyperglycemia. Am J Clin Nutr 2008; 87: 217S-222S
• 26 Woerle HJ, Albrecht M, Linke R, Zschau S, Neumann C, Nicolaus M, Gerich J, Göke B, Schirra J. Importance of changes in gastric emptying for postprandial plasma glucose fluxes in healthy humans. Am J Physiol Endocrinol Metab 2008; 294: E103-E109
• 27 Maggs D, MacDonald I, Nauck MA. Glucose homeostasis and the gastrointestinal tract: insights into the treatment of diabetes. Diabetes Obes Metab 2008; 10: 18-33
• 28 Mitrakou A. Kidney: its impact on glucose homeostasis and hormonal regulation. Diabetes Res Clin Pract 2011; 93 (Suppl. 01) S66-S72
• 29 Kowluru RA, Odenbach S. Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes 2004; 53: 3233-3238
• 30 Mah E, Bruno RS. Postprandial hyperglycemia on vascular endothelial function: mechanisms and consequences. Nutr Res 2012; 32: 727-740
• 31 Klosterbuer AS, Thomas W, Slavin JL. Resistant starch and pullulan reduce postprandial glucose, insulin, and GLP-1, but have no effect on satiety in healthy humans. J Agric Food Chem 2012; 60: 11928-11934
• 32 Hsu CH. Different impacts of metabolic syndrome components on insulin resistance in type 2 diabetes. Int J Endocrinol 2013; 2013: 740419
• 33 Konstantopoulos N, Molero JC, McGee SL, Spolding B, Connor T, de Vries M, Wanyonyi S, Fahey R, Morrison S, Swinton C, Jones S, Cooper A, Garcia-Guerra L, Foletta VC, Krippner G, Andrikopoulos S, Walder KR. Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo. Diabetes 2012; 61: 2146-2154
• 34 Li Y, Chen M, Xuan H, Hu F. Effects of encapsulated propolis on blood glycemic control, lipid metabolism, and insulin resistance in type 2 diabetes mellitus rats. Evid Based Complement Alternat Med 2012; 2012: 981896
• 35 Gan KX, Wang C, Chen JH, Zhu CJ, Song GY. Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats. World J Gastroenterol 2013; 19: 1572-1581
• 36 Ko WC, Liu IM, Chung HH, Cheng JT. Activation of I(2)-imidazoline receptors may ameliorate insulin resistance in fructose-rich chow-fed rats. Neurosci Lett 2008; 448: 90-93
• 37 Consoli A, Nurjhan N, Capani F, Gerich J. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes 1989; 38: 550-557
• 38 Friedrichsen M, Mortensen B, Pehmoller C, Birk JB, Wojtaszewski JF. Exercise-induced AMPK activity in skeletal muscle: Role in glucose uptake and insulin sensitivity. Mol Cell Endocrinol 2013; 366: 204-214
• 39 Kaidanovich-Beilin O, Eldar-Finkelman H. Long-term treatment with novel glycogen synthase kinase-3 inhibitor improves glucose homeostasis in ob/ob mice: molecular characterization in liver and muscle. J Pharmacol Exp Ther 2006; 316: 17-24
• 40 Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005; 436: 356-362
• 41 Bi Y, Sun WP, Chen X, Li M, Liang H, Cai MY, Zhu YH, He XY, Xu F, Weng JP. Effect of early insulin therapy on nuclear factor kappaB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats. Acta Diabetol 2008; 45: 167-178
• 42 Berger J, Biswas C, Vicario PP, Strout HV, Saperstein R, Pilch PF. Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting. Nature 1989; 340: 70-72
• 43 Shieh JP, Cheng KC, Chung HH, Kerh YF, Yeh CH, Cheng JT. Plasma glucose lowering mechanisms of catalpol, an active principle from roots of Rehmannia glutinosa, in streptozotocin-induced diabetic rats. J Agric Food Chem 2011; 59: 3747-3753
• 44 Cheng JT, Huang CC, Liu IM, Tzeng TF, Chang CJ. Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats. Diabetes 2006; 55: 819-825
• 45 Zhang Y, Wang Z, Zhao Y, Zhao M, Wang S, Hua Z, Zhang J. The plasma 5′-AMP acts as a potential upstream regulator of hyperglycemia in type 2 diabetic mice. Am J Physiol Endocrinol Metab 2012; 302: E325-E333