Mechanism of action of Imeglimin: A novel therapeutic agent for type 2 diabetes.
Imeglimin, mechanism, mitochondria, therapeutic, type 2 diabetes
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
06
08
2020
revised:
15
11
2020
accepted:
28
11
2020
pubmed:
4
12
2020
medline:
9
7
2021
entrez:
3
12
2020
Statut:
ppublish
Résumé
Imeglimin is an investigational first-in-class novel oral agent for the treatment of type 2 diabetes (T2D). Several pivotal phase III trials have been completed with evidence of statistically significant glucose lowering and a generally favourable safety and tolerability profile, including the lack of severe hypoglycaemia. Imeglimin's mechanism of action involves dual effects: (a) amplification of glucose-stimulated insulin secretion (GSIS) and preservation of β-cell mass; and (b) enhanced insulin action, including the potential for inhibition of hepatic glucose output and improvement in insulin signalling in both liver and skeletal muscle. At a cellular and molecular level, Imeglimin's underlying mechanism may involve correction of mitochondrial dysfunction, a common underlying element of T2D pathogenesis. It has been observed to rebalance respiratory chain activity (partial inhibition of Complex I and correction of deficient Complex III activity), resulting in reduced reactive oxygen species formation (decreasing oxidative stress) and prevention of mitochondrial permeability transition pore opening (implicated in preventing cell death). In islets derived from diseased rodents with T2D, Imeglimin also enhances glucose-stimulated ATP generation and induces the synthesis of nicotinamide adenine dinucleotide (NAD
Identifiants
pubmed: 33269554
doi: 10.1111/dom.14277
pmc: PMC8049051
doi:
Substances chimiques
Hypoglycemic Agents
0
Insulin
0
Triazines
0
Glucose
IY9XDZ35W2
imeglimin
UU226QGU97
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
664-673Informations de copyright
© 2020 John Wiley & Sons Ltd.
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