Differential effect of hyperglycemia and hyperinsulinemia on pathways of hepatic glycogen repletion

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Abstract
To delineate the roles of hyperglycemia and insulin on the direct vs. indirect pathways of liver glycogen synthesis, we performed euglycemic (group I; n = 8), hyperglycemic (group II; n = 9), and euglycemic pharmacological hyperinsulinemic clamp studies (120 min) with an infusion of [1-13C]glucose in chronically catheterized conscious rats after a 24-h fast. Portal vein plasma glucose concentrations and portal vein plasma insulin concentrations, respectively, obtained at the end of the study in groups I-III were as follows: group I 110 +/- 4 mg/dl, 29 +/- 7 ng/ml; group II 219 +/- 7 mg/dl, 24 +/- 7 ng/ml; and group III 112 +/- 9 mg/dl, 174 +/- 25 ng/ml. Mean liver glycogen concentrations at the end of the three studies were 0.68 +/- 0.07, 1.22 +/- 0.08 (P less than 0.001 compared with groups I and III), and 0.60 +/- 0.17 g/100 g wet wt liver in groups I-III respectively, which yielded hepatic glycogen synthetic rates of 0.16 +/- 0.03, 0.41 +/- 0.04 (P less than 0.001 compared with groups I and III), and 0.13 +/- 0.08 mumol glucosyl U.g liver-1.min-1 in groups I-III, respectively. From the enrichments of 13C in the C-1 and C-6 positions of the glucosyl unit in glycogen compared with the enrichment in the C-1 position in portal vein glucose as determined by 13C- and 1H-NMR, the amount of glycogen synthesized by the direct pathway was calculated to be 18 +/- 2, 41 +/- 3 (P less than 0.0001 compared with groups I and III), and 17 +/- 3% in groups I-III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)