BACKGROUND - Combination immunosuppressive therapy, that often includes prednisone and cyclosporine A (CyA), is commonly used in the treatment of organ transplant patients. We hypothesized that CyA and prednisone treatment would alter the roles of the liver and peripheral tissues in the disposal of carbohydrates from a meal.
METHODS - Using the arteriovenous difference technique, we examined the disposition of an intragastrically delivered mixed meal in eight 24-hour fasted conscious dogs that had received CyA 15 mg x kg(-1) daily and prednisone 5 mg twice daily for 7 consecutive days before study (CyA-prednisone group). The results were compared with those from a group of 13 dogs (control group) receiving the same meal but no drugs.
RESULTS - Neither arterial blood glucose concentrations nor arterial plasma insulin or glucagon concentrations differed significantly between the groups at any time. Cumulative net gut glucose output was equivalent to 43 +/- 9 vs 57% +/- 7% of the glucose in the meal in CyA-prednisone vs control (p = .12). The CyA-prednisone group exhibited greater (p < .05) mean net hepatic glucose uptakes (15.4 +/- 4.6 vs 4.3 +/- 2.2 micromol x kg(-1) x min(-1) and net hepatic fractional extractions of glucose (7.8 +/- 1.6 and 1.5% +/- 1.0%) than the control group. Arterial blood lactate concentrations and net hepatic lactate output were greater in the CyA-prednisone group than the control group (p < .05). Hepatic glycogen content at the end of the study was 2.5-fold greater in the CyA-prednisone group than in the control group (p < .05). The nonhepatic tissues disposed of approximately 91% of the absorbed glucose in the control group but only approximately 26% in the CyA-prednisone group (p < .05).
CONCLUSIONS - CyA-prednisone treatment caused a marked shift in the carbohydrate disposal from a meal, enhancing the hepatic glucose uptake and decreasing peripheral glucose disposal.