title: Administration of Melatonin and Metformin Prevents Deleterious Effects of Circadian Disruption and Obesity in Male Rats.
abstract: Circadian disruption and obesity synergize to predispose to development of type 2 diabetes mellitus (T2DM), signifying that therapeutic targeting of both circadian and metabolic dysfunctions should be considered as a potential treatment approach. To address this hypothesis, we studied rats concomitantly exposed to circadian disruption and diet-induced obesity (CDO), a rat model recently shown to recapitulate phenotypical aspects of obese T2DM (eg, circadian disruption, obesity, insulin resistance, and islet failure). CDO rats were subsequently treated daily (for 12 wk) by timed oral gavage with vehicle, melatonin (a known chronobiotic), metformin, or combination treatment of both therapeutics. Melatonin treatment alone improved circadian activity rhythms, attenuated induction of β-cell failure, and enhanced glucose tolerance. Metformin alone did not modify circadian activity but enhanced insulin sensitivity and glucose tolerance. Importantly, the combination of melatonin and metformin had synergistic actions to modify progression of metabolic dysfunction in CDO rats through improved adiposity, circadian activity, insulin sensitivity, and islet cell failure. This study suggests that management of both circadian and metabolic dysfunctions should be considered as a potential preventative and therapeutic option for treatment of obesity and T2DM.
authors.affiliation: Department of Physiology and Biomedical Engineering (K.R., A.V.M.), Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (A.P.T., J.H., K.V., A.N., A.V.M.), University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Thomas
authors.affiliation: Department of Physiology and Biomedical Engineering (K.R., A.V.M.), Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (A.P.T., J.H., K.V., A.N., A.V.M.), University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hoang
authors.affiliation: Department of Physiology and Biomedical Engineering (K.R., A.V.M.), Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (A.P.T., J.H., K.V., A.N., A.V.M.), University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Kenny
authors.initials: K
authors.lastname: Vongbunyong
authors.affiliation: Department of Physiology and Biomedical Engineering (K.R., A.V.M.), Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (A.P.T., J.H., K.V., A.N., A.V.M.), University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Andrew
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Physiology and Biomedical Engineering (K.R., A.V.M.), Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (A.P.T., J.H., K.V., A.N., A.V.M.), University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Kuntol
authors.initials: K
authors.lastname: Rakshit
authors.affiliation: Department of Physiology and Biomedical Engineering (K.R., A.V.M.), Mayo Clinic School of Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Department of Medicine (A.P.T., J.H., K.V., A.N., A.V.M.), University of California Los Angeles, Los Angeles, California 90095.
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Matveyenko
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000187:drug effects*; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats
chemical_list: D002492:Central Nervous System Depressants; D007004:Hypoglycemic Agents; D008687:Metformin; D008550:Melatonin