PMID- 34093449
OWN - NLM
STAT- MEDLINE
DCOM- 20211223
LR  - 20240402
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 12
DP  - 2021
TI  - Proglucagon-Derived Peptides as Therapeutics.
PG  - 689678
LID - 10.3389/fendo.2021.689678 [doi]
LID - 689678
AB  - Initially discovered as an impurity in insulin preparations, our understanding of 
      the hyperglycaemic hormone glucagon has evolved markedly over subsequent decades. 
      With description of the precursor proglucagon, we now appreciate that glucagon 
      was just the first proglucagon-derived peptide (PGDP) to be characterised. Other 
      bioactive members of the PGDP family include glucagon-like peptides -1 and -2 
      (GLP-1 and GLP-2), oxyntomodulin (OXM), glicentin and glicentin-related 
      pancreatic peptide (GRPP), with these being produced via tissue-specific 
      processing of proglucagon by the prohormone convertase (PC) enzymes, PC1/3 and 
      PC2. PGDP peptides exert unique physiological effects that influence metabolism 
      and energy regulation, which has witnessed several of them exploited in the form 
      of long-acting, enzymatically resistant analogues for treatment of various 
      pathologies. As such, intramuscular glucagon is well established in rescue of 
      hypoglycaemia, while GLP-2 analogues are indicated in the management of short 
      bowel syndrome. Furthermore, since approval of the first GLP-1 mimetic for the 
      management of Type 2 diabetes mellitus (T2DM) in 2005, GLP-1 therapeutics have 
      become a mainstay of T2DM management due to multifaceted and sustainable 
      improvements in glycaemia, appetite control and weight loss. More recently, 
      longer-acting PGDP therapeutics have been developed, while newfound benefits on 
      cardioprotection, bone health, renal and liver function and cognition have been 
      uncovered. In the present article, we discuss the physiology of PGDP peptides and 
      their therapeutic applications, with a focus on successful design of analogues 
      including dual and triple PGDP receptor agonists currently in clinical 
      development.
CI  - Copyright (c) 2021 Lafferty, O'Harte, Irwin, Gault and Flatt.
FAU - Lafferty, Ryan A
AU  - Lafferty RA
AD  - School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
FAU - O'Harte, Finbarr P M
AU  - O'Harte FPM
AD  - School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
FAU - Irwin, Nigel
AU  - Irwin N
AD  - School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
FAU - Gault, Victor A
AU  - Gault VA
AD  - School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
FAU - Flatt, Peter R
AU  - Flatt PR
AD  - School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210518
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Glucagon-Like Peptide 2)
RN  - 55963-74-1 (Proglucagon)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Glucagon/metabolism/*therapeutic use
MH  - Glucagon-Like Peptide 1/*therapeutic use
MH  - Glucagon-Like Peptide 2/*therapeutic use
MH  - Humans
MH  - Proglucagon/metabolism/*therapeutic use
PMC - PMC8171296
OTO - NOTNLM
OT  - GLP-1
OT  - GLP-2
OT  - diabetes
OT  - glucagon
OT  - multi-agonist
OT  - obesity
OT  - oxyntomodulin
OT  - proglucagon
COIS- PF, VG, NI,and FO'H are named on patents filed by Ulster University for the 
      exploitation of incretin-based drugs and other peptide therapeutics. The 
      remaining authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/08 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/01/01
CRDT- 2021/06/07 05:50
PHST- 2021/04/01 00:00 [received]
PHST- 2021/05/05 00:00 [accepted]
PHST- 2021/06/07 05:50 [entrez]
PHST- 2021/06/08 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2021.689678 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2021 May 18;12:689678. doi: 
      10.3389/fendo.2021.689678. eCollection 2021.