Inducement by fat feeding of basal hyperglycemia in rats with abnormal beta-cell function. Model for study of etiology and pathogenesis of NIDDM.
Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogenous disorder characterized by defects in insulin action and secretion. This study was aimed at developing a rat model in which these pathogenic factors might be studied. Male Wistar rats were injected at 2 days of age with 45 or 30 mg/kg streptozocin (STZ) or vehicle (control). Fasting plasma glucose and insulin levels were not significantly different between the two groups between 5 and 8 wk of age. At 8 wk, half of each group was randomly assigned to isocaloric diets high in either fat (59% of calories) or starch (70% of calories). After 1 wk on the diets, 45-mg/kg-STZ-administered fat-fed animals displayed significant fasting hyperglycemia (8.6 +/- 0.2 mM; P less than 0.01), which was exacerbated by the stress of anesthesia and/or cannulation, whereas no changes were observed in any of the other groups before (STZ starch fed, 6.7 +/- 0.1 mM; control fat fed, 6.8 +/- 0.1 mM; control starch fed; 6.4 +/- 0.1 mM) or after anesthesia and/or cannulation. In the 30-mg/kg-STZ animals, fat feeding did not significantly elevate plasma glucose concentration, but a significant hyperglycemic response was seen with anesthesia and/or cannulation. In all STZ groups, substantial impairment of glucose-induced insulin secretion was observed, particularly early-phase insulin secretion. Further studies indicated that STZ animals on a diet conferring normal insulin sensitivity (starch) maintained basal normoglycemia and mildly impaired (i.v.) glucose tolerance despite this gross insulin secretory defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Pascoe
W S
WS
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia.
Storlien
L H
LH
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D013311:Streptozocin; D005947:Glucose