NUTRITIONAL AND METABOLIC CHARACTERIZATION OF A THIAMINE-DEFICIENT RAT MODEL

The effects of a thiamine-deficient diet on plasma and -tissue vitamin concentrations and on whole-body glucose metabolism were assessed. Male Sprague-Dawley rats (175 to 200 g body weight) fed a thiamine-deficient (TD) or nutritionally complete purified diet were used for plasma thiamine mononitrate and monophosphate and for red blood cell and tissue thiamine pyrophosphate (TPP) determinations weekly for up to 5 weeks. Additional rats were used for assessment of basal glucose kinetics by using a primed constant infusion of [3-H-3H]glucose. Plasma thiamine mononitrate levels decreased 60% at 1 week and were undetectable after 5 weeks on the diet. Plasma thiamine monophosphate decreased 80% after 1 week on the TD diet, and levels were undetectable after 4 weeks on the diet. Red blood cell TPP in the TD group decreased progressively with time: 54% at 1 week, 86% at 3 weeks, and 92% at 5 weeks. At 1 and 4 weeks, the decrease in tissue TPP was significant in the liver (65% and 89%, respectively), gut (52% and 94%, respectively), spleen (40% and 60%, respectively), and skeletal muscle (37% and 76%, respectively), with the brain (7% and 84%, respectively) showing the slowest initial rate of depletion. The TD diet did not alter plasma glucose concentrations, but it increased plasma lactate by 75% and plasma pyruvate by 50% to 75%. Rates of hepatic glucose production and peripheral glucose utilization were not different between the control and TD rats at 2 weeks, but they were 25% higher in the TD rats after 6 weeks on the diet. Plasma hormone concentrations were not different between the control and TD animals at 2 weeks. However, after 6 weeks on the diet, plasma insulin levels were 37% lower in the TD group, and glucagon and corticosterone levels were 85% to 97% higher than in the control animals. In general, these changes in whole-body glucose flux induced by the TD diet could not be explained simply by the reduction in food consumption in the deficient animals. In summary, TD resulted in (1) marked reductions in plasma thiamine levels, (2) a progressive decrease in red blood cell TPP content that paralleled that seen for both thiamine monophosphate and TPP in most peripheral tissues, and (3) multiple changes in whole-body carbohydrate metabolism and glucoregulatory hormone concentrations. These changes were documented before any neurologic manifestations of a TD state.