PMID- 17306374
OWN - NLM
STAT- MEDLINE
DCOM- 20070515
LR  - 20240414
IS  - 0163-7258 (Print)
IS  - 0163-7258 (Linking)
VI  - 113
IP  - 3
DP  - 2007 Mar
TI  - Mechanisms of action of glucagon-like peptide 1 in the pancreas.
PG  - 546-93
AB  - Glucagon-like peptide 1 (GLP-1) is a hormone that is encoded in the proglucagon 
      gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted 
      into the blood stream when food containing fat, protein hydrolysate, and/or 
      glucose enters the duodenum. Its particular effects on insulin and glucagon 
      secretion have generated a flurry of research activity over the past 20 years 
      culminating in a naturally occurring GLP-1 receptor (GLP-1R) agonist, exendin 4 
      (Ex-4), now being used to treat type 2 diabetes mellitus (T2DM). GLP-1 engages a 
      specific guanine nucleotide-binding protein (G-protein) coupled receptor (GPCR) 
      that is present in tissues other than the pancreas (brain, kidney, lung, heart, 
      and major blood vessels). The most widely studied cell activated by GLP-1 is the 
      insulin-secreting beta cell where its defining action is augmentation of 
      glucose-induced insulin secretion. Upon GLP-1R activation, adenylyl cyclase (AC) 
      is activated and cAMP is generated, leading, in turn, to cAMP-dependent 
      activation of second messenger pathways, such as the protein kinase A (PKA) and 
      Epac pathways. As well as short-term effects of enhancing glucose-induced insulin 
      secretion, continuous GLP-1R activation also increases insulin synthesis, beta 
      cell proliferation, and neogenesis. Although these latter effects cannot be 
      currently monitored in humans, there are substantial improvements in glucose 
      tolerance and increases in both first phase and plateau phase insulin secretory 
      responses in T2DM patients treated with Ex-4. This review will focus on the 
      effects resulting from GLP-1R activation in the pancreas.
FAU - Doyle, Maire E
AU  - Doyle ME
AD  - Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
FAU - Egan, Josephine M
AU  - Egan JM
LA  - eng
GR  - Z01 AG000214-14/Intramural NIH HHS/United States
GR  - Z01 AG000905-09/Intramural NIH HHS/United States
GR  - Z01 AG000906-09/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Review
DEP - 20061228
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (Venoms)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
RN  - 9P1872D4OL (Exenatide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/drug therapy/*physiopathology
MH  - Enteroendocrine Cells/enzymology
MH  - Exenatide
MH  - Glucagon/metabolism
MH  - Glucagon-Like Peptide 1/metabolism/*physiology
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Glucose/physiology
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin/biosynthesis/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/physiology
MH  - Pancreas/*physiology
MH  - Peptides/pharmacology
MH  - Receptors, Glucagon/*physiology
MH  - Second Messenger Systems/physiology
MH  - Venoms/pharmacology
PMC - PMC1934514
MID - NIHMS20598
EDAT- 2007/02/20 09:00
MHDA- 2007/05/16 09:00
PMCR- 2008/03/01
CRDT- 2007/02/20 09:00
PHST- 2006/11/22 00:00 [received]
PHST- 2006/11/27 00:00 [accepted]
PHST- 2007/02/20 09:00 [pubmed]
PHST- 2007/05/16 09:00 [medline]
PHST- 2007/02/20 09:00 [entrez]
PHST- 2008/03/01 00:00 [pmc-release]
AID - S0163-7258(06)00203-8 [pii]
AID - 10.1016/j.pharmthera.2006.11.007 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2007 Mar;113(3):546-93. doi: 10.1016/j.pharmthera.2006.11.007. 
      Epub 2006 Dec 28.