Interaction of a selective serotonin reuptake inhibitor with insulin in the control of hepatic glucose uptake in conscious dogs.
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 microg x kg(-1) x min(-1) from 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 micromol x kg(-1) x min(-1) in Sal-Ins and Fluv-Ins, respectively (not significant), and 13.3 +/- 2.2 and 20.9 +/- 3.1 micromol x kg(-1) x 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 micromol x kg(-1) x min(-1)). Nonhepatic glucose uptake was reduced in Fluv-INS vs. Sal-INS (20.0 +/- 1.3 vs. 38.4 +/- 5.4 micromol x kg(-1) x 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.
Moore
Mary Courtney
MC
Dept of Molecular Physiology & Biophysics, Vanderbilt Univ. School of Medicine, Nashville, TN 37232-0615, USA. genie.moore@vanderbilt.edu
DiCostanzo
Catherine A
CA
Dardevet
Dominique
D
Lautz
Margaret
M
Farmer
Ben
B
Cherrington
Alan D
AD
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D003243:Consciousness; D004285:Dogs; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D012701:Serotonin / Q000097:blood; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D002244:Carbon; D005230:Fatty Acids, Nonesterified; D016666:Fluvoxamine; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D006003:Glycogen; D007328:Insulin; D019344:Lactic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013004:Somatostatin