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

First Author  Persson K Year  2002
Journal  Acta Physiol Scand Volume  175
Issue  1 Pages  25-8
PubMed ID  11982501 Mgi Jnum  J:103025
Mgi Id  MGI:3608369 Doi  10.1046/j.1365-201X.2002.00977.x
Citation  Persson K, et al. (2002) The neuropeptide PACAP contributes to the glucagon response to insulin-induced hypoglycaemia in mice. Acta Physiol Scand 175(1):25-8
abstractText  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.
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