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

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.