Troglitazone (CS-045) inhibits beta-cell proliferation rate following stimulation of insulin secretion in HIT-T 15 cells

Endocrinology
K OhtaniM Mori

Abstract

Thiazolidinedione analogs are new antidiabetic agents that attenuate peripheral insulin resistance in noninsulin-dependent diabetic patients; however, the effects of these agents on insulin secretion are not known. We determined the short-term and long-term effects of troglitazone (CS-045) on insulin secretion in a Syrian hamster clonal beta-cell line, HIT-T 15 cells. The direct effect of troglitazone (CS-045: 10(-6)-10(-4) M) on insulin secretion was examined in F-12 K incubation medium containing 7 mM glucose. CS-045 significantly stimulated insulin secretion within 10 min at the concentration of 10(-4) M and dose dependently stimulated insulin secretion within 60 min at the concentration of 10(-6)-10(-4) M. The addition of 10(-5) M CS-045 showed an immediate increase of cytoplasmic free Ca2+ concentrations ([Ca2+]i). Removal of extracellular Ca2+ by the addition of 1.5 mM EGTA completely abolished the 10(-4) M CS-045-induced insulin secretion for 10-min. Long-term incubation (24 h) with 10(-4) M CS-045 significantly decreased beta-cell insulin content and inhibited insulin secretion. During a 5-day incubation, CS-045 showed a dose-dependent reduction of insulin secretion measured during the final 24 h. Long-term incubation w...Continue Reading

Citations

Jan 10, 2013·Diabetology & Metabolic Syndrome·Rodrigo N LamounierMaria Lúcia Corrêa-Giannella
Apr 19, 2002·Biochemical Pharmacology·Miriam CnopDaniel G Pipeleers
Jul 9, 2004·British Journal of Pharmacology·Hannah J WeltersNoel G Morgan
Apr 17, 2007·FEBS Letters·R Paul Robertson, Jamie S Harmon
Apr 5, 2003·American Journal of Physiology. Endocrinology and Metabolism·Ken YajimaTakao Saruta
Oct 14, 2004·American Journal of Physiology. Endocrinology and Metabolism·Melanie J LutherPeter M Jones
Nov 19, 2003·Metabolism: Clinical and Experimental·Walter S ZawalichKathleen C Zawalich

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