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

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.

Comprehensive Metabolomic Analysis in Blood, Urine, Fat, and Muscle in Men with Metabolic Syndrome: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Resveratrol after Four Months’ Treatment

“…Stimulation of the PPP pathway is associated with increased insulin resistance, increased NADPH production, and thus, increased production of free fatty acids [31]. Hence, our metabolomics findings may indicate increased glucose availability and utilization through glycolysis and the pentose phosphate pathway, owing to decreased insulin sensitivity in the males receiving resveratrol.…”

Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle

“…Furthermore, we did not observe this phenomenon in response to hu-nNOSμ, despite the fact that hu-nNOSμ and 6-AN produced similar results with regards to suppression of G6PDH and increases in insulin-independent glucose uptake. In individuals with T2D, infusion of a NO donor increases basal rates of leg glucose uptake [39]. Studies in isolated muscle strips have shown that this increased glucose uptake occurs through an insulin-independent signaling mechanism(s) [40].…”

Advanced glycation end products in the pathogenesis of chronic kidney disease

“…14,15 Plasma protein AGEs, such as MG-H1 and 3DG-H, may be increased by dicarbonyl stress; 13 CML and glucosepane may be increased by elevated FL residue precursor and/or decreased FL metabolism; [16][17][18] and pentosidine residue content may be increased by elevated pentosephosphate pathway activity providing increased level of the pentose precursor. 19 AGE residue content of plasma protein is also influenced by decreased residence time of albumin in the vascular compartment by albuminuria, 20 increased transcapillary escape rateinfluenced by hypertension and atherosclerosis; 21 and also by decreased albumin synthesis and catabolism. 22 These confounders suggest AGE residue content of plasma protein has a complex relationship with clinical outcomes in CKD.…”