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HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism
- HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism
- Row, H[Row, Hansang]; Jeong, J[Jeong, Jaekap]; Cho, S[Cho, Sehyung]; Kim, S[Kim, Sungwuk]; Kim, K[Kim, Kyungjin]
- DGIST Authors
- Row, H[Row, Hansang]; Kim, K[Kim, Kyungjin]
- Issue Date
- Biochemical and Biophysical Research Communications, 469(3), 783-789
- Article Type
- 3T3 Cell Line; Agents Affecting Metabolism; AMP-Activated Protein Kinases; AMPK; Analogs and Derivatives; Animal; Animal Cell; Animal Experiment; Animal Model; Animal Tissue; Animals; Antidiabetic Activity; Antidiabetic Agent; Body Weight; C57Bl Mouse; Cell Cycle Protein; Cell Cycle Proteins; Cell Line; Cell Metabolism; Circadian Clock; Circadian Clocks; Circadian Rhythm; Controlled Study; Cryptochrome 1; Diet Induced Obesity; Dose-Response; Drug Effect; Drug Effects; Drug Mechanism; Embryo; Energy Metabolism; Enzyme Activation; Enzyme Phosphorylation; Enzyme Regulation; Gene Expression; Gluconeogenesis; Glucose; Glucose 6 Phosphatase; Glucose Homeostasis; Glucose Metabolism; Hep G2 Cell Line; Hep G2 Cells; HL 271; Human; Humans; Hydroxymethylglutaryl Coenzyme A Reductase Kinase; Hypoglycemic Agents; Insulin; Insulin Sensitivity; Lipid Metabolism; Lipid Metabolites; Metabolic Regulation; Metabolism; Metformin; Mice; Mice, Inbred C57BL; Morning Dosage; Mouse; NIH 3T3 Cells; Non-Human; Obesity; PER2 Protein; Phosphoenolpyruvate Carboxykinase (GTP); Physiological Process; Physiology; Priority Journal; Protein Degradation; Structure-Activity Relationship; Structure Activity Relation; Transcription Factor Clock; Treatment Outcome; Unclassified Drug
- Metformin is a treatment of choice for patients with type 2 diabetes. Its action involves the phosphorylation of 5'-adenosine monophosphate activated protein kinase (AMPK), leading to inhibition of liver gluconeogenesis. The effects of a novel chemical compound derived from metformin, HL271, on molecular and physiological actions involving AMPK and rhythmically-expressed circadian clock genes were investigated. HL271 potently activated AMPK in a dose-dependent manner, and produced shortening of the circadian period and enhanced degradation of the clock genes PER2 and CRY1. Although the molecular effects of HL271 resembled those of metformin, it produced different physiological effects in mice with diet-induced obesity. HL271 did not elicit glucose-lowering or insulin-sensitizing effects, possibly because of altered regulation of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1. This indicated that, although HL271 acted on circadian clock machinery through a similar molecular mechanism to metformin, it differed in its systemic effect on glucose and lipid metabolite regulations. © 2015 Elsevier Inc. All rights reserved.
- Academic Press Inc.
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