Role of Excess Glycogenolysis in Fasting Hyperglycemia Among Pre-Diabetic and Diabetic Zucker (fa/fa) Rats
Sources of plasma glucose and glucose turnover were investigated in 8-week-old (pre-diabetic) and 13-week-old (diabetic) Zucker (fa/fa) rats after a 24-h fast. Intraperitoneal 2 H 2 O was administered and [3,4-13 C 2 ]glucose and [U-13 C 3 ]propionate were infused into conscious active rats. 13 C nuclear magnetic resonance analysis of monoacetone glucose derived from blood glucose indicated that glucose production was increased significantly in 8-and 13-weekold fa/fa rats compared with
... pared with age-matched Zucker (؉/؉) rats, and hepatic glycogen was dramatically higher among fa/fa animals regardless of age. Glycogenolysis, essentially 0 in ؉/؉ rats after a 24-h fast, was significant in fa/fa rats (11 ؎ 6 and 17 ؎ 7% of glucose production in 8-and 13-week-old rats, respectively), even after a 24-h fast. Tricarboxylic acid (TCA) cycle flux and efflux of carbon skeletons from the cycle (cataplerosis) were both significantly higher in fa/fa rats compared with controls, but net gluconeogenesis from the TCA cycle was not higher because products leaving the cycle were returned to the cycle via a pyruvate cycling pathway. Thus, pyruvate cycling flux increased in proportion to TCA cycle flux, leaving net gluconeogenesis unchanged in fa/fa animals compared with control animals. The distribution of 2 H in skeletal muscle glycogen suggested that at least a fraction of glucose molecules entering glycogen pass through phosphomannose isomerase.