Figure 1. Induction of hyperglycemia by a high-fat (48%) diet followed by spontaneous return to toward normoglycemia after switching to regular (17% fat) diets.

(A–D) The durations of exposure to high-fat diets were 1, 2, 4, 7, 9, 18, and 28 days prior to a return to regular diets. The degrees of hyperglycemia were progressively worse and the returns toward normoglycemia were progressively slower as the length of exposure to high-fat diets was increased. All glucose levels were obtained under nonfasting conditions. (E) Insulin levels at the end of the studies were lowest in the ZDF rats fed 45% fat diet exclusively and highest in the animals fed 17% fat diets exclusively. Insulin levels in the 3 groups of animals fed high-fat diets for variable time periods followed by a return to regular diets had intermediate plasma insulin levels. The highest insulin levels during the return to regular diets were in animals with the shortest exposure (9 days) to the high-fat diets, while longer exposures to high-fat diet (18 and 28 days) were associated with increasingly lower insulin levels after return to low-fat diets. However, even in the 9-day reversal study, insulin levels failed to reach the levels observed in the control animals fed 17% fat standard chow diets. Two-tailed Student t tests with Bonferroni correction for multiple comparison testing; **P < 0.01.