Involvement of liver and skeletal muscle in sucrose-induced insulin resistance: dose-response studies.
The ability of dietary sucrose to induce insulin resistance independent of changes in body weight is controversial. In the present study male rats were fed a high-starch (ST) diet (starch 68% of total kcal) ad libitum for 2 wk and then were fed equicalorically either the ST diet or a high-sucrose (SU) diet (sucrose 68% of total kcal) for 8 wk. Euglycemic, hyperinsulinemic (0, 1.2, 4.1, 8, 15 mU.kg-1.min-1, n = 6-8/group per dose) clamps were then used to establish dose-response relationships for glucose kinetics and metabolism. Body weight (513 +/- 3 g) and composition were similar between groups after the 8-wk dietary period. Glucose infusion rates (GIR; mg.kg-1.min-1) were significantly less in SU (0.9 +/- 5.8 +/- 0.6, 14.8 +/- 1.3, and 18 +/- 1.1) than in ST rats (4.1 +/- 0.9, 12.3 +/- 1.2, 22.6 +/- 1.5, and 25.9 +/- 1.8) at 1.2, 4.1, 8, and 15 mU.kg-1.min-1, respectively. Impaired suppression of endogenous glucose production accounted for 46, 43, 23, and 0% of the reduction in GIR in SU rats at 1.2, 4.1, 8, and 15 mU.kg-1.min-1, respectively. Despite basal hyperinsulinemia (38 +/- 2 microU/ml in SU vs. 26 +/- 2 microU/ml in ST rats), liver phosphoenolpyruvate carboxykinase (PEPCK) activity was 50% higher in SU than in ST rats and remained elevated in SU rats (by 30-40%) at the two lower insulin doses. No skeletal muscle glycogen accumulation occurred in SU rats at any of the insulin doses, and glycogen synthase I activity was significantly lower in SU rats at the two highest insulin doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Pagliassotti
M J
MJ
Department of Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Shahrokhi
K A
KA
Moscarello
M
M
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D004040:Dietary Carbohydrates; D004305:Dose-Response Relationship, Drug; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000494:pharmacology*
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D008112:Liver Glycogen; D013395:Sucrose; D006003:Glycogen