Revisiting the concept of incretin and enteroendocrine L-cells as type 2 diabetes mellitus treatment. (June 2022)

• Record Type: Journal Article
• Authors: Lok, Kok-Hou; Wareham, Nicholas J.; Nair, Rajesh Sreedharan; How, Chee Wun; Chuah, Lay-Hong
• Is Part Of: Pharmacological research. Volume 180(2022)
• Publication Date: 2022-06
• Subjects: AA amino acids -- BS bariatric surgery -- CaSR calcium-sensing receptor -- CCK cholecystokinin -- DPP4-i dipeptidyl peptidase-4 inhibitor -- DSPE-PEG2000 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)2000] -- EECs enteroendocrine cells -- FFAR free fatty acid receptors -- GIP glucose-dependent insulinotropic polypeptide -- GIT gastrointestinal tract -- GLP glucagon-like peptide -- GLP-1 glucagon-like peptide-1 -- GLUT-2 glucose transporter 2 -- GPBAR1/TGR5 Gs-coupled bile acid receptors -- GPCRs G-protein coupled receptors -- GPRC6A G-protein coupled receptor family C group 6 subtype A -- HbA1c haemoglobin A1c -- HRQoL patients health-related quality of life -- INSL5 insulin-like peptide 5 -- KATP ATP-sensitive K+ channels -- LNC lipid nanocapsules -- mGluR1/4 metabotropic glutamate receptors 1/4 -- NLC nanostructured lipid carriers -- NT neurotensin -- OXM oxyntomodulin -- PPARδ peroxisome proliferator-activated receptor δ -- PEPT1 proton-dependent intestinal peptide transporter 1 -- PYY peptide YY -- RYGB roux-en-Y gastric bypass -- SCFAs short-chain fatty acids -- SG sleeve gastrectomy -- SGLT-1 sodium-glucose cotransporter 1 -- STR sweet taste receptor -- T1R1/3 type 1 taste receptor subunit 1/3 -- T2DM type 2 diabetes mellitus -- TPH1 tryptophan hydroxylase 1 -- TRPA1 Transient Receptor Potential Ankyrin 1; Bariatric surgery -- Enteroendocrine L-cell -- Incretin -- Pharmaceutical formulation -- Pharmacotherapy; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106237
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: 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. Graphical Abstract: ga1