1. Long-term high-fat feeding leads to severe insulin resistance but not diabetes in Wistar rats
- Author
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Chalkley, Simon M., Hettiarachchi, Manthinda, Chisholm, Donald J., and Kraegen, Edward W.
- Subjects
Insulin resistance -- Risk factors ,Unsaturated fatty acids -- Physiological aspects ,Food habits -- Physiological aspects ,Body composition -- Analysis ,Biological sciences - Abstract
Although lipid excess can impair [beta]-cell function in vitro, short-term high-fat feeding in normal rats produces insulin resistance but not hyperglycemia. This study examines the effect of long-term (10-mo) high polyunsaturated fat feeding on glucose tolerance in Wistar rats. The high fat-fed compared with the chow-fed group was 30% heavier and 60% fatter, with approximately doubled fasting hyperinsulinemia (P < 0.001) but only marginal fasting hyperglycemia (7.5 [+ or -] 0.1 vs. 7.2 [+ or -] 0.1 mmol/l, P < 0.01). Insulin sensitivity was ~67% lower in the high-fat group (P < 0.01). The acute insulin response to intravenous arginine was approximately double in the insulin-resistant high-fat group (P < 0.001), but that to intravenous glucose was similar in the two groups. After the intravenous glucose bolus, plasma glucose decline was slower in the high fat-fed group, confirming mild glucose intolerance. Therefore, despite severe insulin resistance, there was only a mildly elevated fasting glucose level and a relative deficiency in glucose-stimulated insulin secretion; this suggests that a genetic or congenital susceptibility to [beta]-cell impairment is required for overt hyperglycemia to develop in the presence of severe insulin resistance. insulin secretion; arginine; long-chain acyl-coenzyme A; body composition; glucose tolerance
- Published
- 2002