PMID- 31672472
OWN - NLM
STAT- MEDLINE
DCOM- 20210310
LR  - 20210310
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1727
DP  - 2020 Jan 15
TI  - Isoflurane aggravates peripheral and central insulin resistance in high-fat 
      diet/streptozocin-induced type 2 diabetic mice.
PG  - 146511
LID - S0006-8993(19)30565-7 [pii]
LID - 10.1016/j.brainres.2019.146511 [doi]
AB  - Isoflurane anesthesia is reported to induce insulin resistance (IR) in the 
      peripheral tissues. However, researches on the impact of isoflurane on 
      insulin-related metabolism in the central nervous system, especially in type 2 
      diabetes mellitus (T2DM), are scarce. This study sought to explore whether 
      isoflurane anesthesia had a negative effect on insulin sensitivity both in 
      peripheral and central tissues. Moreover, the possible role of isoflurane 
      anesthesia in T2DM mice with pre-existing IR was analyzed. T2DM model in C57BL/6J 
      mice was established by high fat diet (HFD) and single intraperitoneal injection 
      of streptozotocin (STZ, 60 mg/kg). Both HFD/STZ-induced T2DM mice and normal mice 
      received 6 h isoflurane exposure. Blood glucose level and serum insulin 
      concentration were detected and the homeostasis model assessment of IR (HOMA-IR) 
      index was calculated to estimate peripheral IR. Relative levels of genes and 
      proteins in the insulin-dependent signaling pathway in mouse prefrontal cortex 
      and hippocampus were determined to measure central IR. Results indicated that 6 h 
      isoflurane exposure induced hyperglycemia, hyperinsulinemia and raised HOMA-IR 
      index. Meanwhile, phosphorylated insulin receptor substrate-1 (pIRS1) (Ser639) 
      and phosphorylated insulin receptor substrate-2 (pIRS2) (Ser731) were 
      upregulated, while phosphorylated protein kinase B (pAKT) (Ser473) and 
      phosphorylated glycogen synthase kinase-3 beta (pGSK3beta) (Ser9) were downregulated 
      in the prefrontal cortex and hippocampus of anesthetized mice. Notably, 
      isoflurane anesthesia significantly aggravated the degree of central IR in the 
      aspects of gene transcriptions and protein expressions in HFD/STZ-induced T2DM 
      mice with pre-existing IR. This study suggested that isoflurane anesthesia 
      induced peripheral and central IR and aggravated pre-existing insulin resistance 
      in T2DM mice.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Fang, Xin
AU  - Fang X
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China.
FAU - Xia, Tianjiao
AU  - Xia T
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China; Jiangsu Key 
      Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China.
FAU - Xu, Fangxia
AU  - Xu F
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China.
FAU - Ma, Zhengliang
AU  - Ma Z
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China.
FAU - Zhao, Xin
AU  - Zhao X
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China. Electronic 
      address: zhaoxin@nju.edu.cn.
FAU - Gu, Xiaoping
AU  - Gu X
AD  - Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical 
      Department of Nanjing University, Nanjing, Jiangsu 210008, China. Electronic 
      address: xiaopinggu@nju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191028
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Anesthetics, Inhalation)
RN  - 5W494URQ81 (Streptozocin)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Anesthetics, Inhalation/*adverse effects
MH  - Animals
MH  - Diabetes Mellitus, Experimental/*chemically induced
MH  - Diabetes Mellitus, Type 2/*chemically induced
MH  - Diet, High-Fat/adverse effects
MH  - Hippocampus/drug effects
MH  - Hyperglycemia/chemically induced
MH  - Hyperinsulinism/chemically induced
MH  - *Insulin Resistance
MH  - Isoflurane/*adverse effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Prefrontal Cortex/drug effects
MH  - Streptozocin
OTO - NOTNLM
OT  - Central nervous system
OT  - Cognition
OT  - Insulin resistance
OT  - Isoflurane
OT  - Type 2 diabetes mellitus
EDAT- 2019/11/02 06:00
MHDA- 2021/03/11 06:00
CRDT- 2019/11/02 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/09/18 00:00 [revised]
PHST- 2019/10/15 00:00 [accepted]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2021/03/11 06:00 [medline]
PHST- 2019/11/02 06:00 [entrez]
AID - S0006-8993(19)30565-7 [pii]
AID - 10.1016/j.brainres.2019.146511 [doi]
PST - ppublish
SO  - Brain Res. 2020 Jan 15;1727:146511. doi: 10.1016/j.brainres.2019.146511. Epub 
      2019 Oct 28.