Neonatal streptozotocin-induced diabetes mellitus: a model of insulin resistance associated with loss of adipose mass.
The use of experimental models of diabetes mellitus (DM) has been useful in understanding the complex pathogenesis of DM. Streptozotocin (STZ) injected in rats during the neonatal period has usually led to the major features described in diabetic patients (hyperglycemia, polyphagia, polydipsia, polyuria, and abnormal glucose tolerance) in a short period. Diabetes mellitus is a product of low insulin sensibility and pancreatic beta-cell dysfunction. Its process is characterized by a symptomless prediabetic phase before the development of the disease. In this study, we investigated the long-term effects of diabetes induction regarding the cellular metabolic aspects of this model and its similarities with diabetes found in humans. Male Wistar rats (5-day old) were intraperitoneally injected with STZ (150 mg/kg) and followed up for 12 weeks. On the 12th week, animals were decapitated and peri-epididymal fat pads were excised for adipocyte isolation. The following studies were performed: insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake; incorporation of d-[U-(14)C]-glucose into lipids and conversion into (14)CO(2); and insulin binding. The weight gain rate of the STZ-treated group became significantly lower by the eighth week. These rats developed polyphagia, polydipsia, polyuria, and glycosuria, and impaired glucose tolerance. Biological tests with isolated adipocytes revealed a reduction in the insulin receptor number and an impairment in their ability to oxidize glucose as well as to incorporate it into lipids. Interestingly, parallel to reduced body weight, the adipocyte size of STZ rats was significantly small. We concluded that apart of a decrease in pancreatic insulin content, this experimental model of DM promotes a remarkable and sustained picture of insulin resistance in adulthood that is strongly related to a loss in adipose mass.
Takada
Julie
J
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900, Sao Paulo, Brazil.
Machado
Magaly A
MA
Peres
Sidney B
SB
Brito
Luciana C
LC
Borges-Silva
Cristina N
CN
Costa
Cecília E M
CE
Fonseca-Alaniz
Miriam H
MH
Andreotti
Sandra
S
Lima
Fabio Bessa
FB
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D005947:Glucose