title: Loss-of-function mutation of the galanin gene is associated with perturbed islet function in mice.
abstract: The neuropeptide galanin is expressed in sympathetic nerve terminals that surround islet cells and inhibits insulin secretion. To explore its role for islet function, we studied mice with a loss-of-function mutation in the galanin gene [galanin knockout (KO) mice]. Intravenous 2-deoxy-glucose, which activates both the sympathetic and parasympathetic branches of the autonomic nervous system, caused an initial (1-5 min) inhibition of insulin secretion that was impaired in galanin KO mice (P = 0.027), followed by a subsequent stimulation of insulin secretion that was augmented in galanin KO mice (P < 0.01). Similar effects were seen after chemical sympathectomy by 6-hydroxydopamine. In contrast, galanin KO mice had a reduced insulin response to glucose, both in vivo (P < 0.001) and in isolated islets (P < 0.001), and to arginine, both in vivo (P = 0.012) and in vitro (P = 0.018). During an iv glucose tolerance test, galanin KO mice had impaired glucose disposal (P = 0.005) due to a reduced insulin response (P < 0.001) and a reduced insulin-independent glucose elimination (glucose effectiveness; P = 0.040). Insulin sensitivity, as judged by a euglycemic, hyperinsulinemic clamp technique, was slightly increased in galanin KO mice (P = 0.032). We conclude that 1) galanin may contribute to sympathetic influences inhibiting insulin secretion in mice, and 2) galanin KO mice have a reduced glucose-induced insulin secretion.
authors.affiliation: Department of Medicine, Lund University, B11 Biomedical Centre, SE-221 84 Lund, Sweden. Bo.Ahren@med.lu.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: David
authors.initials: D
authors.lastname: Wynick
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001835:Body Weight; D003847:Deoxyglucose / Q000494:pharmacology; D019004:Galanin / Q000235:genetics* / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D000963:Antimetabolites; D007004:Hypoglycemic Agents; D007328:Insulin; D019004:Galanin; D005934:Glucagon; D003847:Deoxyglucose; D005947:Glucose