Interaction of a selective serotonin reuptake inhibitor with insulin in the control of hepatic glucose uptake in conscious dogs

Abstract

Whether hyperinsulinemia is required for stimulation of net hepatic glucose uptake (NHGU) by a selective serotonin reuptake inhibitor (SSRI) was examined in four groups of conscious 42-h-fasted dogs, using arteriovenous difference and tracer ([3-3H]glucose) techniques. Experiments consisted of equilibration (−120 to −30 min), basal (−30 to 0 min), and experimental periods (Exp; 0–240 min). During Exp, somatostatin, intraportal insulin [at basal (Ins groups) or 4-fold basal rates (INS groups)], basal intraportal glucagon, and peripheral glucose (to double hepatic glucose load) were infused. In the Fluv-Ins ( n = 7) and Fluv-INS groups ( n = 6), saline was infused intraportally from 0 to 90 min ( P1), and fluvoxamine was infused intraportally at 2 μg·kg−1·min−1from 90 to 240 min ( P2). Sal-Ins ( n = 9) and Sal-INS ( n = 8) received intraportal saline in P1 and P2. NHGU during P2 was 8.4 ± 1.4 and 6.9 ± 2.3 μmol·kg−1·min−1in Sal-Ins and Fluv-Ins, respectively (not significant), and 13.3 ± 2.2 and 20.9 ± 3.1 μmol·kg−1·min−1( P < 0.05) in Sal-INS and Fluv-INS. Unidirectional (tracer-determined) hepatic glucose uptake was twofold greater ( P < 0.05) in Fluv-INS than Sal-INS. Net hepatic carbon retention during P2 was significantly greater in Fluv-INS than Sal-INS (18.5 ± 2.7 vs. 12.2 ± 1.9 μmol·kg−1·min−1). Nonhepatic glucose uptake was reduced in Fluv-INS vs. Sal-INS (20.0 ± 1.3 vs. 38.4 ± 5.4 μmol·kg−1·min−1, P < 0.05). Intraportal fluvoxamine enhanced NHGU and net hepatic carbon retention in the presence of hyperinsulinemia but not euinsulinemia, suggesting that hepatocyte-targeted SSRIs may reduce postprandial hyperglycemia.