Abstract
This study was initiated to develop an animal model of type 2 diabetes in a non-obese,
outbred rat strain that replicates the natural history and metabolic characteristics
of the human syndrome and is suitable for pharmaceutical research. Male Sprague-Dawley
rats (n = 31), 7 weeks old, were fed normal chow (12% of calories as fat), or high-fat
diet (40% of calories as fat) for 2 weeks and then injected with streptozotocin (STZ,
50 mg/kg intravenously). Before STZ injection, fat-fed rats had similar glucose concentrations
to chow-fed rats, but significantly higher insulin, free fatty acid (FFA), and triglyceride
(TG) concentrations (P < .01 to .0001). Plasma insulin concentrations in response
to oral glucose (2 g/kg) were increased 2-fold by fat feeding (P < .01), and adipocyte
glucose clearance under maximal insulin stimulation was significantly reduced (P <
.001), suggesting that fat feeding induced insulin resistance. STZ injection increased
glucose (P < .05), insulin (P < .05), FFA (P < .05), and TG (P < .0001) concentrations
in fat-fed rats (Fat-fed/STZ rats) compared with chow-fed, STZ-injected rats (Chow-fed/STZ
rats). Fat-fed/STZ rats were not insulin deficient compared with normal chow-fed rats,
but had hyperglycemia and a somewhat higher insulin response to an oral glucose challenge
(both P < .05). In addition, insulin-stimulated adipocyte glucose clearance was reduced
in Fat-fed/STZ rats compared with both chow-fed and Chow-fed/STZ rats (P < .001).
Finally, Fat-fed/STZ rats were sensitive to the glucose lowering effects of metformin
and troglitazone. In conclusion, Fat-fed/STZ rats provide a novel animal model for
type 2 diabetes, simulates the human syndrome, and is suitable for the testing of
antidiabetic compounds. Copyright © 2000 by W.B. Saunders Company
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Further reading
- Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus.N Engl J Med. 1993; 329: 1988-1992
- Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic patients.Ann Intern Med. 1990; 113: 909-915
- Plasma insulin, C-peptide, and proinsulin concentrations in obese and nonobese individuals with varying degrees of glucose tolerance.J Clin Endocrinol Metab. 1993; 76: 44-48
- Low-dose streptozotocin-induced diabetes in the spontaneously hypertensive rat.Metabolism. 1991; 40: 335-337
- Evidence of abnormalities of insulin metabolism in rats with spontaneous hypertension.Metabolism. 1988; 37: 303-305
- Resistance to insulin-stimulated glucose uptake in adipocytes isolated from spontaneously hypertensive rats.Diabetes. 1989; 38: 1155-1160
- In vivo insulin resistance in individual peripheral tissues of the high fat fed rat: Assessment by euglycemic clamp plus deoxyglucose administration.Diabetologia. 1986; 29: 192-198
- Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats.Diabetes. 1991; 40: 1397-1403
- Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure and obesity in the rat.Am J Physiol. 1986; 251: E576-E583
- Improvement in in vitro insulin action after one month of insulin therapy in obese noninsulin-dependent diabetics.J Clin Invest. 1983; 72: 1901-1909
- In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus.J Clin Invest. 1983; 72: 1246-1254
- Metabolism of isolated fat cells. 1. Effects of hormones on glucose metabolism and lipolysis.J Biol Chem. 1964; 239: 375-380
- Determination of adipose cell size and number in suspensions of isolated rat and human adipose cells.J Lipid Res. 1978; 19: 269-273
- Dietary and drug treatment of hyperlipidemia in diabetes.Diabetes. 1974; 23: 913-918
- Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities.J Clin Endocrinol Metab. 1991; 72: 934-944
- Relation of insulin deficiency to impaired insulin action in NIDDM adult rats given streptozocin as neonates.Diabetes. 1989; 38: 610-617
- Diabetogenic effect of streptozocin in the rat during the perinatal period.Diabetes. 1974; 23: 889-895
- Islet secretion in a new experimental model for non-insulin-dependent diabetes.Diabetes. 1981; 30: 590-595
- Inducement of basal hyperglycemia in rats with abnormal B-cell function by fat-feeding: Model for study of aetiology and pathogenesis of NIDDM.Diabetes. 1990; 39: 226-233
- Insulin action and determinants of glycaemia in a rat model of type 2 (non-insulin-dependent) diabetes mellitus.Diabetologia. 1992; 35: 208-215
- Zucker diabetic fatty rat as a model for non-insulin-dependent diabetes mellitus.Inst Lab Anim Resources News. 1990; 32: 16-19
Article info
Publication history
Accepted:
May 12,
2000
Received:
August 4,
1988
0026-0495/00/4911-0017$10.00/0Identification
Copyright
© 2000 W.B. Saunders Company. Published by Elsevier Inc. All rights reserved.
