Activated Glucose-6-phosphate Dehydrogenase is Associated with Insulin Resistance by Upregulating Pentose and Pentosidine in Diet-induced Obesity of Rats

F. Wang; Y. Zhao; Y. Niu; C. Wang; M. Wang; Y. Li; C. Sun

doi:10.1055/s-0032-1323727

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2012; 44(13): 938-942
DOI: 10.1055/s-0032-1323727

Original Basic

Activated Glucose-6-phosphate Dehydrogenase is Associated with Insulin Resistance by Upregulating Pentose and Pentosidine in Diet-induced Obesity of Rats

Authors

F. Wang

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China
Y. Zhao

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China
Y. Niu

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China
C. Wang

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China
M. Wang

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China
Y. Li

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China
C. Sun

¹Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China

Abstract

Recent studies have shown that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme for the pentose phosphate pathway, was involved in insulin resistance via reduced nicotinamide adenine dinucleotide phosphate, while the roles of pentose were not examined. In the present study, the association of G6PD, pentose, and pentosidine with insulin resistance was investigated in diet-induced obesity of rats. Male Wistar rats were fed a high-fat diet for 6 weeks to generate obesity-prone (OP, n=14) and obesity-resistant (OR, n=14) rats. The levels of G6PD, pentose, and pentosidine, and oxidative stress were analyzed in serum and tissues. The OP rats, compared to the OR and control rats, had a significant increase in body weight (16.2% and 12.8%), serum triglyceride (43.4% and 12.3), and free fatty acids (49.5% and 23.6%), and developed marked insulin resistance. G6PD activities were increased in the pancreas and liver with upregulated pentose levels in serum, pancreas, and liver of OP rats. Pentosidine levels were increased only under the condition of high pentose levels and oxidative stress status in serum and pancreas of OP rats. G6PD activities in pancreas and liver, pentose levels in serum, pancreas, and liver, and pentosidine levels in serum and pancreas were positively correlated with homeostasis model of assessment-insulin resistance. Our results suggest that the upregulation of G6PD causes an increase in the accumulation of pentose and pentosidine, which might be associated with insulin resistance in the condition of obesity.

Key words

pentose phosphate pathway - oxidative stress - advanced glycation end products

Full Text

References

References
1 McGarry JD. Disordered metabolism in diabetes: have we underemphasized the fat component?. J Cell Biochem 1994; 55 (Suppl) 29-38
2 Boden G. Free fatty acids – the link between obesity and insulin resistance. Endocr Pract 2001; 7: 44-51
3 Fasshauer M, Paschke R, Stumvoll M. Adiponectin, obesity, and cardiovascular disease. Biochimie 2004; 86: 779-784
4 Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 2011; 50: 567-575
5 Misra A. C-reactive protein in young individuals: problems and implications for Asian Indians. Nutrition 2004; 20: 478-481
6 Park J, Rho HK, Kim KH, Choe SS, Lee YS, Kim JB. Overexpression of glucose-6-phosphate dehydrogenase is associated with lipid dysregulation and insulin resistance in obesity. Mol Cell Biol 2005; 25: 5146-5157
7 Park J, Choe SS, Choi AH, Kim KH, Yoon MJ, Suganami T, Ogawa Y, Kim JB. Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals. Diabetes 2006; 55: 2939-2949
8 Kletzien RF, Harris PK, Foellmi LA. Glucose-6-phosphate dehydrogenase: a “housekeeping” enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. FASEB J 1994; 8: 174-181
9 Gupte RS, Floyd BC, Kozicky M, Georg S, Ungvari ZI, Neito V, Wolin MS, Gupte SA. Synergistic activation of glucose-6-phosphate dehydrogenase and NAD(P)H oxidase by Src kinase elevates superoxide in type 2 diabetic, Zucker fa/fa, rat liver. Free Radic Biol Med 2009; 47: 219-228
10 Serpillon S, Floyd BC, Gupte RS, Georg S, Kozicky M, Neito V, Rechia F, Stanley W, Wolin MS, Gupte SA. Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH. Am J Physiol Heart Circ Physiol 2009; 297: H153-H162
11 Tan KC, Shiu SW, Wong Y, Tam X. Serum advanced glycation end products is associated with insulin resistance. Diabetes Metab Res Rev 2011; 27: 488-492
12 Tahara N, Yamagishi S, Matsui T, Takeuchi M, Nitta Y, Kodama N, Mizoguchi M, Imaizumi T. Serum levels of advanced glycation end products (AGEs) are independent correlates of insulin resistance in nondiabetic subjects. Cardiovasc Ther 2012; 30: 42-48
13 Unoki H, Bujo H, Yamagishi S, Takeuchi M, Imaizumi T, Saito Y. Advanced glycation end products attenuate cellular insulin sensitivity by increasing the generation of intracellular reactive oxygen species in adipocytes. Diabetes Res Clin Pract 2007; 76: 236-244
14 Sell DR, Monnier VM. Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. J Biol Chem 1989; 264: 21597-21602
15 Sugiyama S, Miyata T, Ueda Y, Tanaka H, Maeda K, Kawashima S, Van Yperscle de Strihou C, Kurokawa K. Plasma levels of pentosidine in diabetic patients: an advanced glycation end product. J Am Soc Nephrol 1998; 9: 1681-1688
16 Makita Z, Radoff S, Rayfield EJ, Yang Z, Skolnik E, Delaney V, Friedman EA, Cerami A, Vlassara H. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991; 325: 836-842
17 Miyata T, Ueda Y, Shinzato T, Iida Y, Tanaka S, Kurokawa K, van Ypersele de Strihou C, Maeda K. Accumulation of albumin-linked and free-form pentosidine in the circulation of uremic patients with end-stage renal failure: renal implications in the pathophysiology of pentosidine. J Am Soc Nephrol 1996; 7: 1198-1206
18 Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis. Br J Rheumatol 1997; 36: 637-642
19 Hein G, Wiegand R, Lehmann G, Stein G, Franke S. Advanced glycation end-products pentosidine and N epsilon-carboxymethyllysine are elevated in serum of patients with osteoporosis. Rheumatology (Oxford) 2003; 42: 1242-1246
20 Liu L, Li Y, Guan C, Li K, Wang C, Feng R, Sun C. Free fatty acid metabolic profile and biomarkers of isolated post-challenge diabetes and type 2 diabetes mellitus based on GC-MS and multivariate statistical analysis. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878: 2817-2825
21 Pickavance LC, Buckingham RE, Wilding JP. Insulin-sensitizing action of rosiglitazone is enhanced by preventing hyperphagia. Diabetes Obes Metab 2001; 3: 171-180
22 Umeda M, Kanda T, Murakami M. Effects of angiotensin II receptor antagonists on insulin resistance syndrome and leptin in sucrose-fed spontaneously hypertensive rats. Hypertens Res 2003; 26: 485-492
23 Bolognani L, Coppi G, Zambotti V. Determination of pentoses. Cellular and Molecular Life Sciences 1961; 17: 67-68
24 Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 1978; 186: 189-195
25 Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588-590
26 Bessman JD, Gardner FH. Platelet size in thrombocytopenia due to sepsis. Surg Gynecol Obstet 1983; 156: 177-180
27 Dyer DG, Blackledge JA, Thorpe SR, Baynes JW. Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J Biol Chem 1991; 266: 11654-11660
28 Grandhee SK, Monnier VM. Mechanism of formation of the Maillard protein cross-link pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. J Biol Chem 1991; 266: 11649-11653
29 Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 2008; 57: 1446-1454