PMID- 29908010
OWN - NLM
STAT- MEDLINE
DCOM- 20181030
LR  - 20181030
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 42
IP  - 10
DP  - 2018 Sep
TI  - Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes 
      rats through activation of autophagy.
PG  - 1282-1291
LID - 10.1002/cbin.11015 [doi]
AB  - Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (T2DM). This 
      study aimed to explore the effects of rapamycin, a specific inhibitor of kinase 
      mammalian target of rapamycin (mTOR), on IR in T2DM rats, and to validate whether 
      the underlying mechanism was associated with autophagy. In this study, the model 
      of T2DM rats was established by feeding the animals with a high-fat diet (HFD) 
      and intraperitoneal injection of streptozotocin (STZ). Diabetic rats were 
      randomly divided into model of T2DM control group (DM-C, n = 15), metformin group 
      (DM-M, n = 15), rapamycin group (DM-Rapa, n = 15), 3-methyladenine (3-MA) group 
      (DM-3-MA, n = 15), and rapamycin + 3-MA group (DM-Rapa-3-MA, n = 15). Rats in 
      different treatment groups were given by corresponding therapy from gastric tube. 
      Meanwhile, normal control group was established (n = 10). As expected, HFD- and 
      STZ- induced T2DM rats exhibited significantly impaired glucose tolerance, 
      reduced insulin sensitivity, dysglycemia and dyslipidemia, aggravated hepatic 
      steatosis, enhanced hepatic inflammation, elevated p-mTOR, and suppressed hepatic 
      autophagy. Importantly, rapamycin and metformin significantly ameliorated IR, 
      relieved disorders of glucose and lipid metabolism, reduced inflammatory level, 
      inhibited mTOR, and promoted autophagy. Importantly, the autophagy inhibitor 3-MA 
      significantly reversed the effects exerted by rapamycin. Collectively, our study 
      suggests that rapamycin improved IR and hepatic steatosis in T2DM rats via 
      activation of autophagy.
CI  - (c) 2018 International Federation for Cell Biology.
FAU - Zhou, Wan
AU  - Zhou W
AD  - Department of Endocrinology, Anhui Provincial Hospital, The First Affiliated 
      Hospital of USTC, Division of Life Sciences and Medicine, University of Science 
      and Technology of China, No. 17 Lujiang Road, Hefei, Anhui 230001, China.
FAU - Ye, Shandong
AU  - Ye S
AD  - Department of Endocrinology, Anhui Provincial Hospital, The First Affiliated 
      Hospital of USTC, Division of Life Sciences and Medicine, University of Science 
      and Technology of China, No. 17 Lujiang Road, Hefei, Anhui 230001, China.
LA  - eng
PT  - Journal Article
DEP - 20180708
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Diabetes Mellitus, Type 2/complications/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Disease Models, Animal
MH  - Fatty Liver/*drug therapy/physiopathology
MH  - Glucose/metabolism
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin/metabolism
MH  - Insulin Resistance/physiology
MH  - Lipid Metabolism/drug effects
MH  - Liver/drug effects
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sirolimus/metabolism/*pharmacology
OTO - NOTNLM
OT  - IR
OT  - T2DM
OT  - autophagy
OT  - rapamycin
EDAT- 2018/06/17 06:00
MHDA- 2018/10/31 06:00
CRDT- 2018/06/17 06:00
PHST- 2017/12/13 00:00 [received]
PHST- 2018/05/27 00:00 [accepted]
PHST- 2018/06/17 06:00 [pubmed]
PHST- 2018/10/31 06:00 [medline]
PHST- 2018/06/17 06:00 [entrez]
AID - 10.1002/cbin.11015 [doi]
PST - ppublish
SO  - Cell Biol Int. 2018 Sep;42(10):1282-1291. doi: 10.1002/cbin.11015. Epub 2018 Jul 
      8.