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-week-old fa/fa rats compared 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.
Jin
Eunsook S
ES
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8568, USA. eunsook.jin@utsouthwestern.edu
Park
Byung-Hyun
BH
Sherry
A Dean
AD
Malloy
Craig R
CR
D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000737:chemistry / Q000378:metabolism; D002952:Citric Acid Cycle / Q000502:physiology; D003920:Diabetes Mellitus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D050261:Glycogenolysis / Q000502:physiology*; D006943:Hyperglycemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D011236:Prediabetic State / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose; D005947:Glucose