Troglitazone acutely activates AMP-activated protein kinase and inhibits insulin secretion from beta cells. 2007

Xiao Wang, and Libin Zhou, and Li Shao, and Lei Qian, and Xuelian Fu, and Guo Li, and Tianhong Luo, and Yanyun Gu, and Fengying Li, and Jiping Li, and Sheng Zheng, and Min Luo
Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Changes in AMP-activated protein kinase (AMPK) activity contribute to the regulation of insulin secretion. Troglitazone has been shown to lower serum insulin levels and protect beta cell function. The aim of the present study was to examine the effects of troglitazone on AMPK activity and insulin secretion in beta cells. Isolated rat islets and MIN6 cells were treated for a short (1 h) or a long time (20 h) with troglitazone. One-hour troglitazone treatment activated AMPK and inhibited both glucose-stimulated insulin secretion (GSIS) and the response of insulin secretion to combined stimuli of glucose and palmitate. Long (20 h) treatment with troglitazone caused a sustained phosphorylation of AMPK and acetyl-CoA carboxylase, and increased GSIS after withdrawal of the drug. This study provided evidence that troglitazone activated AMPK in beta cells. In addition to the insulin-sensitizing effects in peripheral tissues, troglitazone also directly inhibits insulin hypersecretion by the elevated glucose and fatty acids, and thus protects beta cells from glucolipotoxicity.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007202 Indicators and Reagents Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499) Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297 Male Males
D010168 Palmitates Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid. Hexadecanoates,Palmitate
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002839 Chromans Benzopyrans saturated in the 2 and 3 positions. Dihydrobenzopyrans
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000077288 Troglitazone A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity. 5-(4-((6-Hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benzyl)-2,4-thiazolidinedione) - T,CS 045,CS-045,Prelay,Rezulin,CS045

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