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

• Published in: American journal of physiology: endocrinology and metabolism 2005-03, Vol.51 (3), p.E556-E563
• Main Authors: MOORE, Mary Courtney, DICOSTANZO, Catherine A, DARDEVET, Dominique, LAUTZ, Margaret, FARMER, Ben, CHERRINGTON, Alan D
• Format: Article
• Language: English
• Subjects: Antidepressants; Biological and medical sciences; Dogs; Endocrine system; Fundamental and applied biological sciences. Psychology; Hypoglycemia; Insulin; Liver; Vertebrates: endocrinology
• ISSN: 0193-1849; 1522-1555

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(symbol)kg-1(symbol)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(symbol)kg-1(symbol)min-1 in Sal-Ins and Fluv-Ins, respectively (not significant), and 13.3 +/- 2.2 and 20.9 +/- 3.1 micromol(symbol)kg-1(symbol)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(symbol)kg-1(symbol)min-1). Nonhepatic glucose uptake was reduced in Fluv-INS vs. Sal-INS (20.0 +/- 1.3 vs. 38.4 +/- 5.4 micromol(symbol)kg-1(symbol)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. [PUBLICATION ABSTRACT]