PMID- 30907023
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20211204
IS  - 1099-0844 (Electronic)
IS  - 0263-6484 (Linking)
VI  - 37
IP  - 3
DP  - 2019 Apr
TI  - Telmisartan protects against high glucose/high lipid-induced apoptosis and 
      insulin secretion by reducing the oxidative and ER stress.
PG  - 161-168
LID - 10.1002/cbf.3383 [doi]
AB  - Telmisartan, an angiotensin II receptor blocker, has been widely used for 
      hypertension. It has also been reported to improve insulin sensitivity in animal 
      models of obesity and diabetic patients by targeting to the peroxisome 
      proliferator-activated receptor (PPAR)-gamma. High glucose/high lipid (HG/HL)-induced 
      apoptosis of pancreatic beta-cells impairs its function of insulin secretion and is 
      generally believed to be the key factor in the development of diabetes. In this 
      study, we investigated whether telmisartan exerted a protective effect against 
      HG/HL-induced apoptosis and insulin secretion in vitro as well as in vivo; 10-muM 
      telmisartan treatment significantly reduced HG (25 mM) or/and HL (0.4 mM palmitic 
      acid) induced-cell apoptosis and greatly improved insulin secretion in INS-1 
      pancreatic beta-cells, which is consistent in an obesity rat model induced by HG/HL 
      diets. Furthermore, telmisartan treatment markedly reduced the protein level of 
      GRP78, CHOP, and caspase 12, while increasing anti-apoptotic Bcl-2 protein 
      expression. Moreover, telmisartan treatment significantly reduced intracellular 
      ROS levels. Mechanistically, we demonstrated that PPARgamma signaling pathway may be 
      involved in the telmisartan protective effects, which were blocked by a PPARgamma 
      blocker, GW9662. In conclusion, the protective effect of telmisartan was mediated 
      by an anti-ER stress-induced apoptotic and anti-oxidative pathway. SIGNIFICANCE 
      OF THIS STUDY: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder 
      worldwide pathologically characterized by hyperglycemia and insulin resistance. 
      Long-term high glucose in the blood has been proposed to induce pancreatic beta-cell 
      loss and is generally believed to be the key factor in the development of 
      diabetes. In the present study, we demonstrated that telmisartan, a common drug 
      used for hypertension treatment, has a protective effect against high 
      glucose/high lipid-induced cell apoptosis and greatly improves the insulin 
      secretion function by inhibiting the oxidative stress and ER stress. Furthermore, 
      this protective effect of telmisartan is mediated by the PPAR-gamma signal pathway, 
      which may provide a potential strategy against T2DM.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Wang, Yan
AU  - Wang Y
AUID- ORCID: 0000-0002-1916-0958
AD  - Department of Endocrinology, The First Hospital of Shanxi Medical University, 
      Taiyuan, Shan Xi, China.
FAU - Xue, Jingjing
AU  - Xue J
AUID- ORCID: 0000-0002-7327-2352
AD  - Department of Endocrinology, The First Hospital of Shanxi Medical University, 
      Taiyuan, Shan Xi, China.
FAU - Li, Yan
AU  - Li Y
AUID- ORCID: 0000-0003-3781-5396
AD  - Department of Endocrinology, The First Hospital of Shanxi Medical University, 
      Taiyuan, Shan Xi, China.
FAU - Zhou, Xin
AU  - Zhou X
AUID- ORCID: 0000-0002-2940-1356
AD  - Department of Pathophysiology, Shanxi Medical University, Taiyuan, Shan Xi, 
      China.
FAU - Qiao, Shun
AU  - Qiao S
AUID- ORCID: 0000-0003-1121-4170
AD  - Department of Endocrinology, The First Hospital of Shanxi Medical University, 
      Taiyuan, Shan Xi, China.
FAU - Han, Dewu
AU  - Han D
AUID- ORCID: 0000-0002-2497-7495
AD  - Department of Pathophysiology, Shanxi Medical University, Taiyuan, Shan Xi, 
      China.
LA  - eng
GR  - 2017037/Health Commission of Shanxi Province, China/
PT  - Journal Article
DEP - 20190325
PL  - England
TA  - Cell Biochem Funct
JT  - Cell biochemistry and function
JID - 8305874
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Anilides)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Lipids)
RN  - 0 (PPAR gamma)
RN  - 0 (Reactive Oxygen Species)
RN  - IY9XDZ35W2 (Glucose)
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - Anilides/pharmacology
MH  - Antihypertensive Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Glucose/*antagonists & inhibitors/pharmacology
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin-Secreting Cells/drug effects/metabolism
MH  - Lipids/*antagonists & inhibitors/pharmacology
MH  - Oxidative Stress/*drug effects
MH  - PPAR gamma/antagonists & inhibitors/metabolism
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Structure-Activity Relationship
MH  - Telmisartan/antagonists & inhibitors/*pharmacology
OTO - NOTNLM
OT  - ER stress
OT  - apoptosis
OT  - high glucose/high lipid
OT  - insulin secretion
OT  - oxidative stress
OT  - telmisartan
EDAT- 2019/03/25 06:00
MHDA- 2019/05/09 06:00
CRDT- 2019/03/26 06:00
PHST- 2018/04/10 00:00 [received]
PHST- 2019/01/14 00:00 [revised]
PHST- 2019/01/29 00:00 [accepted]
PHST- 2019/03/25 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2019/03/26 06:00 [entrez]
AID - 10.1002/cbf.3383 [doi]
PST - ppublish
SO  - Cell Biochem Funct. 2019 Apr;37(3):161-168. doi: 10.1002/cbf.3383. Epub 2019 Mar 
      25.