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

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13 Scopus citations

Abstract

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 2H2O was administered and [3,4-13C2]glucose and [U-13C 3]propionate were infused into conscious active rats. 13C 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 2H in skeletal muscle glycogen suggested that at least a fraction of glucose molecules entering glycogen pass through phosphomannose isomerase.

Original languageEnglish (US)
Pages (from-to)777-785
Number of pages9
JournalDiabetes
Volume56
Issue number3
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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