Long-term high-fat feeding leads to severe insulin resistance but not diabetes in Wistar rats.
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 +/- 0.1 vs. 7.2 +/- 0.1 mmol/l, P < 0.01). Insulin sensitivity was approximately 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.
Chalkley
Simon M
SM
Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia 2010.
Hettiarachchi
Manthinda
M
Chisholm
Donald J
DJ
Kraegen
Edward W
EW
D000214:Acyl Coenzyme A / Q000032:analysis; D000375:Aging; D000818:Animals; D001120:Arginine; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D003920:Diabetes Mellitus / Q000209:etiology* / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D005215:Fasting; D020022:Genetic Predisposition to Disease; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000209:etiology; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000032:analysis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000032:analysis; D015430:Weight Gain
D000214:Acyl Coenzyme A; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D006003:Glycogen; D001120:Arginine