PMID- 27653034
OWN - NLM
STAT- MEDLINE
DCOM- 20170526
LR  - 20220410
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 157
IP  - 12
DP  - 2016 Dec
TI  - Administration of Melatonin and Metformin Prevents Deleterious Effects of 
      Circadian Disruption and Obesity in Male Rats.
PG  - 4720-4731
AB  - 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 beta-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.
FAU - Thomas, Anthony P
AU  - Thomas AP
AD  - 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.
FAU - Hoang, Jonathan
AU  - Hoang J
AD  - 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.
FAU - Vongbunyong, Kenny
AU  - Vongbunyong K
AD  - 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.
FAU - Nguyen, Andrew
AU  - Nguyen A
AD  - 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.
FAU - Rakshit, Kuntol
AU  - Rakshit K
AD  - 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.
FAU - Matveyenko, Aleksey V
AU  - Matveyenko AV
AD  - 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.
LA  - eng
GR  - R01 DK098468/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20160921
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
CIN - Endocrinology. 2016 Dec;157(12 ):4545-4549. PMID: 27911146
MH  - Adiposity/*drug effects
MH  - Animals
MH  - Central Nervous System Depressants/pharmacology/therapeutic use
MH  - Circadian Rhythm/*drug effects
MH  - Glucose Intolerance/*drug therapy/metabolism
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Insulin Resistance/physiology
MH  - Male
MH  - Melatonin/*pharmacology/therapeutic use
MH  - Metformin/*pharmacology/therapeutic use
MH  - Obesity/*drug therapy/metabolism
MH  - Rats
PMC - PMC5133345
EDAT- 2016/09/23 06:00
MHDA- 2017/05/27 06:00
PMCR- 2017/12/01
CRDT- 2016/09/23 06:00
PHST- 2016/09/23 06:00 [pubmed]
PHST- 2017/05/27 06:00 [medline]
PHST- 2016/09/23 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - EN-16-1309 [pii]
AID - 10.1210/en.2016-1309 [doi]
PST - ppublish
SO  - Endocrinology. 2016 Dec;157(12):4720-4731. doi: 10.1210/en.2016-1309. Epub 2016 
      Sep 21.