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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
Authors
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
2016-01-15
Citation
Biochemical and Biophysical Research Communications, 469(3), 783-789
Type
Article
Article Type
Article
Keywords
3T3 Cell LineAgents Affecting MetabolismAMP-Activated Protein KinasesAMPKAnalogs and DerivativesAnimalAnimal CellAnimal ExperimentAnimal ModelAnimal TissueAnimalsAntidiabetic ActivityAntidiabetic AgentBody WeightC57Bl MouseCell Cycle ProteinCell Cycle ProteinsCell LineCell MetabolismCircadian ClockCircadian ClocksCircadian RhythmControlled StudyCryptochrome 1Diet Induced ObesityDose-ResponseDrug EffectDrug EffectsDrug MechanismEmbryoEnergy MetabolismEnzyme ActivationEnzyme PhosphorylationEnzyme RegulationGene ExpressionGluconeogenesisGlucoseGlucose 6 PhosphataseGlucose HomeostasisGlucose MetabolismHep G2 Cell LineHep G2 CellsHL 271HumanHumansHydroxymethylglutaryl Coenzyme A Reductase KinaseHypoglycemic AgentsInsulinInsulin SensitivityLipid MetabolismLipid MetabolitesMetabolic RegulationMetabolismMetforminMiceMice, Inbred C57BLMorning DosageMouseNIH 3T3 CellsNon-HumanObesityPER2 ProteinPhosphoenolpyruvate Carboxykinase (GTP)Physiological ProcessPhysiologyPriority JournalProtein DegradationStructure-Activity RelationshipStructure Activity RelationTranscription Factor ClockTreatment OutcomeUnclassified Drug
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.
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesETC1. Journal Articles


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