Revisiting the concept of incretin and enteroendocrine L-cells as type 2 diabetes mellitus treatment.

Autor: Lok KH; School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia. Electronic address: Lok.KokHou@monash.edu., Wareham NJ; School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia; MRC Epidemiology Unit, University of Cambridge, Institute of Metabolic Science, Cambridge, UK. Electronic address: Nick.wareham@mrc-epid.cam.ac.uk., Nair RS; School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia. Electronic address: RajeshSreedharan.Nair@monash.edu., How CW; School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia. Electronic address: How.CheeWun@monash.edu., Chuah LH; School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia. Electronic address: alice.chuah@monash.edu.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2022 Jun; Vol. 180, pp. 106237. Date of Electronic Publication: 2022 Apr 26.
DOI: 10.1016/j.phrs.2022.106237
Abstrakt: The significant growth in type 2 diabetes mellitus (T2DM) prevalence strikes a common threat to the healthcare and economic systems globally. Despite the availability of several anti-hyperglycaemic agents in the market, none can offer T2DM remission. These agents include the prominent incretin-based therapy such as glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 inhibitors that are designed primarily to promote GLP-1R activation. Recent interest in various therapeutically useful gastrointestinal hormones in T2DM and obesity has surged with the realisation that enteroendocrine L-cells modulate the different incretins secretion and glucose homeostasis, reflecting the original incretin definition. Targeting L-cells offers promising opportunities to mimic the benefits of bariatric surgery on glucose homeostasis, bodyweight management, and T2DM remission. Revising the fundamental incretin theory is an essential step for therapeutic development in this area. Therefore, the present review explores enteroendocrine L-cell hormone expression, the associated nutrient-sensing mechanisms, and other physiological characteristics. Subsequently, enteroendocrine L-cell line models and the latest L-cell targeted therapies are reviewed critically in this paper. Bariatric surgery, pharmacotherapy and new paradigm of L-cell targeted pharmaceutical formulation are discussed here, offering both clinician and scientist communities a new common interest to push the scientific boundary in T2DM therapy.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: