Insulin-like growth factor-I improves glucose utilization in tumor necrosis factor-treated rats under hyperinsulinemic-euglycemic conditions.
The purpose of this study was to determine the effects of insulin-like growth factor-I (IGF-I) on glucose metabolism in normal and tumor necrosis factor (TNF)-treated rats under euglycemic and hyperinsulinemic conditions. During a hyperinsulinemic clamp (10 mU/kg.min), rats further received either saline or IGF-I (3.33 micrograms/kg.min) infusion for 2 hours. Glucose kinetics were determined with [3H-3]-glucose. Glucose utilization in peripheral tissues was examined by glucose uptake using [14C-2]-deoxyglucose (14C-DG) and by glycogen content in select tissues. The results showed that TNF infusion significantly decreased the rate of glucose infusion required to maintain euglycemia. TNF decreased glycogen content significantly in liver and marginally in abdominis muscle. TNF also decreased glucose uptake in muscle, although the decrease was only statistically significant compared with IGF-I infusion. In addition, TNF significantly reduced plasma IGF-I concentration. However, during hyperinsulinemic and euglycemic conditions, exogenous IGF-I significantly increased glucose uptake in muscle and glycogen storage in the liver and abdominis muscle in both saline- and TNF-treated groups. IGF-I normalized each of the effects of TNF in the rats, including those on plasma IGF-I, glucose uptake in muscle, and glycogen content in liver and abdominis muscle. These data suggest that under hyperinsulinemic and euglycemic conditions, TNF-treated rats, although resistant to insulin, have a normal response to IGF-I, indicating that the TNF-induced defect in the insulin pathway may not be a step in the IGF-I pathway.
Ling
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Laboratory of Nutrition/Infection, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Sierra
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Bistrian
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BR
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D005947:Glucose