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Am J Physiol Endocrinol Metab 248: E500-E506, 1985;
0193-1849/85 $5.00
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AJP - Endocrinology and Metabolism, Vol 248, Issue 5 500-E506, Copyright © 1985 by American Physiological Society

ARTICLES

Abnormal oral glucose tolerance in genetically obese (fa/fa) rats

E. Ionescu, J. F. Sauter and B. Jeanrenaud

The effect of intravenous glucose or tolbutamide administration on plasma glucose and insulin levels was compared with that following spontaneous ingestion of glucose in freely moving 6- to 7-wk- and 13- to 14-wk-old lean and obese (fa/fa) rats. Irrespective of age, the obese rats had a normal blood glucose tolerance when glucose or tolbutamide load was given intravenously, whereas the glucose ingestion [oral glucose tolerance test (OGTT) caused a marked glucose intolerance that became more pronounced with the duration of the syndrome. This suggests that factors other than insulin resistance could play a role in the occurrence of abnormal OGTT in obese rats. When blood insulin levels were expressed as percent change over base line and when compared with age-matched normal rats, the 6- to 7-wk obese rats showed a normal and even higher beta-cell responsiveness to intravenous or oral glucose as well as to tolbutamide. In contrast, the 13- to 14-wk obese rats presented a decreased beta-cell responsiveness to all such stimuli. Thus the beta-cell function of obese rats worsens with time. Inasmuch as 13- to 14-wk-old obese fa/fa rats have insulin resistance, high basal glycemia, and abnormal oral glucose tolerance, they can be viewed as a potential model of type II diabetes.


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