Islet function phenotype in gastrin-releasing peptide receptor gene-deficient mice.
Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin secretion. To explore whether islet GRP contributes to neurally mediated insulin secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR-deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows that GRPR is the receptor subtype mediating GRP- induced insulin secretion and that GRPR- deleted mice are tools for studying the physiological role of islet GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin response to glucose by a mechanism inhibited by ganglionic blockade; 2) increased insulin responsiveness also to the cholinergic agonist carbachol, but not to arginine; 3) impaired insulin and glucagon responses to autonomic nerve activation by 2-deoxyglucose; 4) normal islet adaptation to high fat-induced insulin resistance and fasting; and 5) normal islet cytoarchitecture, as revealed by immunocytochemistry of insulin and glucagon. In conclusion, 1) GRPR is the receptor subtype mediating the islet effects of GRP; 2) GRP contributes to insulin secretion induced by activation of the autonomic nerves; and 3) deletion of GRPR is compensated by increased cholinergic sensitivity.[1]References
- Islet function phenotype in gastrin-releasing peptide receptor gene-deficient mice. Persson, K., Pacini, G., Sundler, F., Ahrén, B. Endocrinology (2002) [Pubmed]
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