Effect of High Fat Feeding on Glucose Tolerance in Neonatally Streptozotocin‐Treated Rats at 3 and 6 Months of Age

: In the rat, a high fat intake is believed to be associated with an increased risk for the development of glucose intolerance by inducing insulin resistance. The aim of this study was to investigate whether reduced insulin production may also play a role. Rats were treated with 0, 30, 60, and 90 mg of streptozotocin (STZ)/kg of body weight on the day of birth (0, 30, 60, and 90 nSTZ rats). At 3 or 6 months of age, glucose tolerance was assessed by the intravenous glucose tolerance test (IVGTT). STZ dose-dependently decreased first- and second-phase insulin responses and correspondingly impaired glucose tolerance. Following a 3-week high fat diet (HFD: 60% of calories as corn oil), insulin responses were higher in control as well as in STZ-treated rats both at 3 and 6 months of age. In 3-month-old rats this was accompanied by unchanged or increased glucose levels following the glucose load, whereas in 6-month-old 0 and 30 nSTZ rats glucose tolerance was slightly improved. After 6 weeks of HFD in 6-month-old rats, glucose tolerance was impaired compared to that after 3 weeks of HFD despite higher insulin responses. Continuing the HFD for up to 12 weeks further impaired glucose tolerance, but insulin responses were decreased compared to those after 6 weeks of HFD. These results indicate that very low dose neonatal STZ administration impairs glucose tolerance through decreased overall insulin responses. This may possibly be due to a reduction of B-cell number rather than an alteration of B-cell function. No clear evidence exists that a high fat intake per se negatively influences glucose-induced insulin responses, but this may become apparent after longer periods of high fat feeding.