PMID- 35487405
OWN - NLM
STAT- MEDLINE
DCOM- 20220527
LR  - 20230309
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Print)
IS  - 1043-6618 (Linking)
VI  - 180
DP  - 2022 Jun
TI  - Revisiting the concept of incretin and enteroendocrine L-cells as type 2 diabetes 
      mellitus treatment.
PG  - 106237
LID - S1043-6618(22)00182-7 [pii]
LID - 10.1016/j.phrs.2022.106237 [doi]
AB  - 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.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Lok, Kok-Hou
AU  - Lok KH
AD  - School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, 
      Selangor, Malaysia. Electronic address: Lok.KokHou@monash.edu.
FAU - Wareham, Nicholas J
AU  - Wareham NJ
AD  - 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.
FAU - Nair, Rajesh Sreedharan
AU  - Nair RS
AD  - School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, 
      Selangor, Malaysia. Electronic address: RajeshSreedharan.Nair@monash.edu.
FAU - How, Chee Wun
AU  - How CW
AD  - School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, 
      Selangor, Malaysia. Electronic address: How.CheeWun@monash.edu.
FAU - Chuah, Lay-Hong
AU  - Chuah LH
AD  - School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, 
      Selangor, Malaysia. Electronic address: alice.chuah@monash.edu.
LA  - eng
GR  - MC_UU_00006/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220426
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Incretins)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
MH  - Glucagon-Like Peptide 1/metabolism
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Glucose/metabolism
MH  - Hypoglycemic Agents/therapeutic use
MH  - Incretins/therapeutic use
MH  - L Cells
MH  - Mice
PMC - PMC7614293
MID - EMS157810
OTO - NOTNLM
OT  - Bariatric surgery
OT  - Enteroendocrine L-cell
OT  - Incretin
OT  - Pharmaceutical formulation
OT  - Pharmacotherapy
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2022/04/30 06:00
MHDA- 2022/05/28 06:00
PMCR- 2023/03/08
CRDT- 2022/04/29 19:26
PHST- 2022/02/08 00:00 [received]
PHST- 2022/04/08 00:00 [revised]
PHST- 2022/04/22 00:00 [accepted]
PHST- 2022/04/30 06:00 [pubmed]
PHST- 2022/05/28 06:00 [medline]
PHST- 2022/04/29 19:26 [entrez]
PHST- 2023/03/08 00:00 [pmc-release]
AID - S1043-6618(22)00182-7 [pii]
AID - 10.1016/j.phrs.2022.106237 [doi]
PST - ppublish
SO  - Pharmacol Res. 2022 Jun;180:106237. doi: 10.1016/j.phrs.2022.106237. Epub 2022 
      Apr 26.