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Experimental hypothalamic or genetic obesity in the non-insulin-dependent diabetic rat

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Non-insulin-dependent diabetes was obtained in adult rats by neonatal administration of streptozotocin (100 mg/kg). Obesity was obtained in the same animals either by a ventromedial hypothalamic lesion in adult non-insulindependent diabetic Wistar rats, or by using genetically obese Zucker rats. In diabetic rats, weight gain was similar to that in non-diabetic rats, whether hyperphagia was due to a ventromedial hypothalamic lesion or to a genetic factor. Glucose-induced insulin release in vivo was increased in obese diabetic rats compared with non-diabetic rats. Despite this enhanced insulin secretion, both diabetic ‘fatty’ Zucker rats and diabetic rats with hypothalamic obesity showed a deterioration of glucose tolerance. Moreover, about one-third developed overt diabetes with permanent or transient glycosuria. We conclude that when insulin-deficient rats are made hyperphagic, they are able to increase their insulin secretion and become obese. In some of these animals the occurrence of obesity aggravates the diabetes. The obese diabetic rat appears to be a suitable laboratory model for the study of the relationship between obesity and diabetes.


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Portha, B., Goursot, R., Giroix, M.H. et al. Experimental hypothalamic or genetic obesity in the non-insulin-dependent diabetic rat. Diabetologia 25, 51–55 (1983). https://doi.org/10.1007/BF00251897

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Key words

  • Non-insulin-dependent diabetes
  • obesity, ventromedial hypothalamic lesion
  • fatty Zucker rat
  • streptozotocin
  • insulin secretion
  • glucose tolerance