Role of excess glycogenolysis in fasting hyperglycemia among pre-diabetic and diabetic Zucker (fa/fa) rats

Diabetes. 2007 Mar;56(3):777-85. doi: 10.2337/db06-0717.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Animals
  • Blood Glucose / chemistry
  • Blood Glucose / metabolism
  • Citric Acid Cycle / physiology
  • Diabetes Mellitus / metabolism*
  • Glucose / metabolism
  • Glycogenolysis / physiology*
  • Hyperglycemia / metabolism*
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / metabolism
  • Prediabetic State / metabolism*
  • Rats
  • Rats, Zucker


  • Blood Glucose
  • Glucose