PMID- 38028990
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 1178-7007 (Print)
IS  - 1178-7007 (Electronic)
IS  - 1178-7007 (Linking)
VI  - 16
DP  - 2023
TI  - Roux-en-Y Gastric Bypass Improves Insulin Sensitivity in Obese Rats with Type 2 
      Diabetes Mellitus by Regulating the Grin3a/AMPK Signal Axis in Hypothalamic 
      Arcuate Nucleus.
PG  - 3617-3629
LID - 10.2147/DMSO.S430445 [doi]
AB  - OBJECTIVE: The objective of this study was to explore the effects and related 
      mechanisms of Roux-en-Y gastric bypass (RYGB) on insulin sensitivity in obese 
      rats with type 2 diabetes mellitus (T2DM). METHODS: The obese T2DM rat model was 
      constructed by feeding a high-fat diet and injecting streptozotocin (STZ), and 
      treated with RYGB. Grin3a shRNA was injected into the bilateral hypothalamic 
      arcuate nucleus (ARC) to knockdown the Grin3a expression on T2DM rats. Eight 
      weeks after operation, the body weight, fasting blood glucose (FBG), fasting 
      serum insulin (FSI), homeostatic model assessment of insulin resistance 
      (HOMA-IR), and plasma triglyceride (TG) levels were assessed. Hematoxylin & eosin 
      (H&E) staining was adopted to observe the white adipose tissue (WAT) of rats. 
      Western blot and qRT-PCR were used to detect the expression of Grin3a, adenosine 
      5' monophosphate-activated protein kinase (AMPK) and p-AMPK in ARC of rats. 
      Later, the plasmid over-expressing or knocking down Grin3a was transfected into 
      differentiated 3T3-L1 adipocytes, and the TG level and the formation of lipid 
      droplets in adipocyte were assessed by TG kit and oil red O staining. The 
      expression of lipogenic transcription factors in cells was detected by qRT-PCR. 
      RESULTS: RYGB reduced FBG, FSI, HOMA-IR and plasma TG levels in T2DM rats while 
      increasing Grin3a expression and p-AMPK/AMPK ratio in ARC. Knockdown of Grin3a 
      not only reversed the decrease of FBG, FSI, HOMA-IR and plasma TG levels in T2DM 
      rats induced by RYGB, but also reversed the up-regulation of p-AMPK/AMPK ratio in 
      ARC affected by RYGB. Moreover, knocking down Grin3a significantly increased the 
      TG level, promoted the formation of lipid droplets and up-regulated the 
      expressions of lipogenic transcription factors in adipocytes. CONCLUSION: RYGB 
      improved the insulin sensitivity, reduced the plasma TG level and lessens the fat 
      accumulation in obese T2DM rats by regulating the Grin3a/AMPK signal in ARC.
CI  - (c) 2023 Zhang et al.
FAU - Zhang, Li-Hai
AU  - Zhang LH
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an, People's Republic of China.
AD  - Six Wards of General Surgery, The First Affiliated Hospital of Jiamusi 
      University, Jiamusi, People's Republic of China.
FAU - Wang, Jiao
AU  - Wang J
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an, People's Republic of China.
AD  - Six Wards of General Surgery, The First Affiliated Hospital of Jiamusi 
      University, Jiamusi, People's Republic of China.
FAU - Tan, Bai-Hong
AU  - Tan BH
AD  - Six Wards of General Surgery, The First Affiliated Hospital of Jiamusi 
      University, Jiamusi, People's Republic of China.
FAU - Yin, Yan-Bin
AU  - Yin YB
AD  - Six Wards of General Surgery, The First Affiliated Hospital of Jiamusi 
      University, Jiamusi, People's Republic of China.
FAU - Kang, Yu-Ming
AU  - Kang YM
AD  - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of 
      Basic Medical Sciences, Xi'an, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20231110
PL  - New Zealand
TA  - Diabetes Metab Syndr Obes
JT  - Diabetes, metabolic syndrome and obesity : targets and therapy
JID - 101515585
PMC - PMC10644885
OTO - NOTNLM
OT  - Grin3a/AMPK
OT  - RYGB
OT  - Roux-en-Y gastric bypass
OT  - obesity
OT  - type 2 diabetes mellitus
COIS- The authors declare that they have no competing interests.
EDAT- 2023/11/29 18:42
MHDA- 2023/11/29 18:43
PMCR- 2023/11/10
CRDT- 2023/11/29 17:20
PHST- 2023/08/10 00:00 [received]
PHST- 2023/10/21 00:00 [accepted]
PHST- 2023/11/29 18:43 [medline]
PHST- 2023/11/29 18:42 [pubmed]
PHST- 2023/11/29 17:20 [entrez]
PHST- 2023/11/10 00:00 [pmc-release]
AID - 430445 [pii]
AID - 10.2147/DMSO.S430445 [doi]
PST - epublish
SO  - Diabetes Metab Syndr Obes. 2023 Nov 10;16:3617-3629. doi: 10.2147/DMSO.S430445. 
      eCollection 2023.