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HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism

Title
HL271, a novel chemical compound derived from metformin, differs from metformin in its effects on the circadian clock and metabolism
Author(s)
Row, HansangJeong, JaekapCho, SehyungKim, SungwukKim, Kyungjin
Issued Date
2016-01-15
Citation
Biochemical and Biophysical Research Communications, v.469, no.3, pp.783 - 789
Type
Article
Author Keywords
AMPKCell metabolismCircadian clockGluconeogenesisLipid metabolitesMetformin
Keywords
Cell Cycle ProteinCell Cycle ProteinsCell LineCell MetabolismCircadian ClockCircadian ClocksCircadian RhythmControlled StudyCryptochrome 1DEGRADATIONDiet Induced ObesityDose ResponseDrug EffectDrug EffectsDrug MechanismembryoENERGYEnergy MetabolismEnzyme ActivationEnzyme PhosphorylationEnzyme RegulationGene ExpressionGluconeogenesisGlucoseGlucose 6 PhosphataseGlucose HomeostasisGlucose MetabolismHep G2 CellsHepg2 Cell LineHl 271HumanHumansHydroxymethylglutaryl Coenzyme A Reductase KinaseHypoglycemic AgentsInsulinInsulin SensitivityKINASELipid MetabolismLipid MetabolitesMetabolic RegulationMetabolismMetforminMiceMice, Inbred C57BLMOLECULAR-MECHANISMSMorning DosageMouseNIH 3T3 CellsNonhumanObesityPER2 ProteinPhosphoenolpyruvate Carboxykinase (GTP)PhosphorylationPhysiological ProcessPhysiologyPriority JournalProtein DegradationRHYTHMSStructure-Activity RelationshipStructure Activity RelationTranscription Factor CLOCKTreatment OutcomeUnclassified Drug3T3 Cell LineACTIVATIONAgents Affecting MetabolismAmp-Activated Protein KinasesAMPKAnalogs and DerivativesAnimalAnimal CellAnimal ExperimentAnimal ModelAnimal TissueAnimalsAntidiabetic ActivityAntidiabetic AgentArticleBody WeightC57BL MouseCANCER
ISSN
0006-291X
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/2737
DOI
10.1016/j.bbrc.2015.11.069
Publisher
Academic Press Inc.
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