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The neuropeptide PACAP contributes to the glucagon response to insulin-induced hypoglycaemia in mice.

Persson, K and Ahrén, Bo LU (2002) In Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00 175(1). p.25-28
Abstract
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide in the autonomic nerves innervating the pancreatic islets and previous studies have shown that it stimulates insulin and glucagon secretion. It is known that autonomic nerve activation contributes to the glucagon response to hypoglycaemia. In the present study, we evaluated whether PACAP is involved in this glucagon response by examining the glucagon response to insulin-induced hypoglycaemia in mice genetically deleted of the specific PACAP receptor, the PAC1 receptor. We found that insulin (1 U kg-1 ip) reduced circulating glucose to a hypoglycaemic level of approximately 2.5 mmol L-1 in PAC1R-/- mice and their wild-type counterparts with no... (More)
The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide in the autonomic nerves innervating the pancreatic islets and previous studies have shown that it stimulates insulin and glucagon secretion. It is known that autonomic nerve activation contributes to the glucagon response to hypoglycaemia. In the present study, we evaluated whether PACAP is involved in this glucagon response by examining the glucagon response to insulin-induced hypoglycaemia in mice genetically deleted of the specific PACAP receptor, the PAC1 receptor. We found that insulin (1 U kg-1 ip) reduced circulating glucose to a hypoglycaemic level of approximately 2.5 mmol L-1 in PAC1R-/- mice and their wild-type counterparts with no difference between the groups. However, the glucagon response to this hypoglycaemia was markedly impaired in the PAC1R-/- mice. Thus, after 120 min, plasma glucagon was 437 +/- 79 ng L-1 in wild-type mice vs. only 140 +/- 36 ng L-1 in PAC1R-/- mice (P=0.004). In contrast, the glucagon response to intravenously administered arginine (0.25 g kg-1) was the same in the two groups of mice. We conclude that PACAP through activation of PAC1 receptors contribute to the glucagon response to insulin-induced hypoglycaemia. Therefore, the glucagon response to hypoglycaemia is dependent not only on the classical neurotransmitters but also on the neuropeptide PACAP. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00
volume
175
issue
1
pages
25 - 28
publisher
Wiley-Blackwell
external identifiers
  • wos:000175690300004
  • pmid:11982501
  • scopus:0036098449
ISSN
0001-6772
DOI
10.1046/j.1365-201X.2002.00977.x
language
English
LU publication?
yes
id
80672c7a-d4fd-4e8f-803f-220ac4268614 (old id 107948)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11982501&dopt=Abstract
date added to LUP
2007-06-29 15:22:44
date last changed
2017-11-27 13:21:39
@article{80672c7a-d4fd-4e8f-803f-220ac4268614,
  abstract     = {The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide in the autonomic nerves innervating the pancreatic islets and previous studies have shown that it stimulates insulin and glucagon secretion. It is known that autonomic nerve activation contributes to the glucagon response to hypoglycaemia. In the present study, we evaluated whether PACAP is involved in this glucagon response by examining the glucagon response to insulin-induced hypoglycaemia in mice genetically deleted of the specific PACAP receptor, the PAC1 receptor. We found that insulin (1 U kg-1 ip) reduced circulating glucose to a hypoglycaemic level of approximately 2.5 mmol L-1 in PAC1R-/- mice and their wild-type counterparts with no difference between the groups. However, the glucagon response to this hypoglycaemia was markedly impaired in the PAC1R-/- mice. Thus, after 120 min, plasma glucagon was 437 +/- 79 ng L-1 in wild-type mice vs. only 140 +/- 36 ng L-1 in PAC1R-/- mice (P=0.004). In contrast, the glucagon response to intravenously administered arginine (0.25 g kg-1) was the same in the two groups of mice. We conclude that PACAP through activation of PAC1 receptors contribute to the glucagon response to insulin-induced hypoglycaemia. Therefore, the glucagon response to hypoglycaemia is dependent not only on the classical neurotransmitters but also on the neuropeptide PACAP.},
  author       = {Persson, K and Ahrén, Bo},
  issn         = {0001-6772},
  language     = {eng},
  number       = {1},
  pages        = {25--28},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00},
  title        = {The neuropeptide PACAP contributes to the glucagon response to insulin-induced hypoglycaemia in mice.},
  url          = {http://dx.doi.org/10.1046/j.1365-201X.2002.00977.x},
  volume       = {175},
  year         = {2002},
}