Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes.

Glucokinase diabetes therapy. glucokinase regulator glucokinase regulatory protein glucose homeostasis

Journal

Mini reviews in medicinal chemistry
ISSN: 1875-5607
Titre abrégé: Mini Rev Med Chem
Pays: Netherlands
ID NLM: 101094212

Informations de publication

Date de publication:
23 Aug 2023
Historique:
received: 29 01 2023
revised: 19 06 2023
accepted: 13 07 2023
medline: 24 8 2023
pubmed: 24 8 2023
entrez: 24 8 2023
Statut: aheadofprint

Résumé

The glucokinase regulator (GCKR) gene encodes an inhibitor of the glucokinase enzyme (GCK), found only in hepatocytes and responsible for glucose metabolism. A common GCKR coding variation has been linked to various metabolic traits in genome-wide association studies. Rare GCKR polymorphisms influence GKRP activity, expression, and localization. Despite not being the cause, these variations are linked to hypertriglyceridemia. Because of their crystal structures, we now better understand the molecular interactions between GKRP and the GCK. Finally, small molecules that specifically bind to GKRP and decrease blood sugar levels in diabetic models have been identified. GCKR allelic spectrum changes affect lipid and glucose homeostasis. GKRP dysfunction has been linked to a variety of molecular causes, according to functional analysis. Numerous studies have shown that GKRP dysfunction is not the only cause of hypertriglyceridemia, implying that type 2 diabetes could be treated by activating liver-specific GCK via small molecule GKRP inhibition. The review emphasizes current discoveries concerning the characteristic roles of glucokinase and GKRP in hepatic glucose metabolism and diabetes. This information has influenced the growth of directed molecular therapies for diabetes, which has improved our understanding of lipid and glucose physiology.

Identifiants

pubmed: 37612862
pii: MRMC-EPUB-133998
doi: 10.2174/1389557523666230823151927
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Ajita Paliwal (A)

Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.

Vartika Paliwal (V)

Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.

Smita Jain (S)

Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.

Sarvesh Paliwal (S)

Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.

Swapnil Sharma (S)

Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.

Classifications MeSH