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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/E556    most recent 00405.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Moore, M. C. Articles by Cherrington, A. D. Search for Related Content PubMed PubMed Citation Articles by Moore, M. C. Articles by Cherrington, A. D.

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

¹Department of Molecular Physiology and Biophysics and ²Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 27 August 2004 ; accepted in final form 29 October 2004

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^–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 µmol·kg^–1·min^–1 in 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.

glycemia; liver; fluvoxamine