PMID- 34360682
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210823
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 15
DP  - 2021 Jul 24
TI  - Favorable Effects of GLP-1 Receptor Agonist against Pancreatic beta-Cell Glucose 
      Toxicity and the Development of Arteriosclerosis: "The Earlier, the Better" in 
      Therapy with Incretin-Based Medicine.
LID - 10.3390/ijms22157917 [doi]
LID - 7917
AB  - Fundamental pancreatic beta-cell function is to produce and secrete insulin in 
      response to blood glucose levels. However, when beta-cells are chronically exposed 
      to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and 
      secretion are decreased together with reduced expression of insulin transcription 
      factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic 
      beta-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the beta-cell membrane and 
      thereby enhances insulin secretion, suppresses apoptotic cell death and increase 
      proliferation of beta-cells. However, GLP-1R expression in beta-cells is reduced under 
      diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable 
      effects on beta-cells at an early stage of T2DM compared to an advanced stage. On 
      the other hand, it has been drawing much attention to the idea that GLP-1 
      signaling is important in arterial cells; GLP-1 increases nitric oxide, which 
      leads to facilitation of vascular relaxation and suppression of arteriosclerosis. 
      However, GLP-1R expression in arterial cells is also reduced under diabetic 
      conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at 
      an early stage of T2DM. Furthermore, it has been reported recently that 
      administration of GLP-1RA leads to the reduction of cardiovascular events in 
      various large-scale clinical trials. Therefore, we think that it would be better 
      to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis 
      and protection of beta-cells against glucose toxicity in routine medical care.
FAU - Kaneto, Hideaki
AU  - Kaneto H
AUID- ORCID: 0000-0001-7898-1943
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Kimura, Tomohiko
AU  - Kimura T
AUID- ORCID: 0000-0003-3986-9494
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Shimoda, Masashi
AU  - Shimoda M
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Obata, Atsushi
AU  - Obata A
AUID- ORCID: 0000-0003-4984-4098
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Sanada, Junpei
AU  - Sanada J
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Fushimi, Yoshiro
AU  - Fushimi Y
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Nakanishi, Shuhei
AU  - Nakanishi S
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Mune, Tomoatsu
AU  - Mune T
AD  - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 
      Kurashiki 701-0192, Japan.
FAU - Kaku, Kohei
AU  - Kaku K
AD  - General Medical Center, Kawasaki Medical School, Kurashiki 701-0192, Japan.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210724
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Incretins)
SB  - IM
MH  - Arteriosclerosis/*drug therapy/etiology/prevention & control
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Humans
MH  - Hyperglycemia/*complications
MH  - Incretins/pharmacology/*therapeutic use
MH  - Insulin-Secreting Cells/*drug effects/physiology
PMC - PMC8348147
OTO - NOTNLM
OT  - GLP-1 receptor agonist
OT  - arteriosclerosis
OT  - glucose toxicity
OT  - incretin-based medicine
OT  - pancreatic beta-cells
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/08 06:00
MHDA- 2021/08/24 06:00
PMCR- 2021/07/24
CRDT- 2021/08/07 01:07
PHST- 2021/06/22 00:00 [received]
PHST- 2021/07/21 00:00 [revised]
PHST- 2021/07/22 00:00 [accepted]
PHST- 2021/08/07 01:07 [entrez]
PHST- 2021/08/08 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2021/07/24 00:00 [pmc-release]
AID - ijms22157917 [pii]
AID - ijms-22-07917 [pii]
AID - 10.3390/ijms22157917 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 24;22(15):7917. doi: 10.3390/ijms22157917.