title: Endogenous somatostatin is critical in regulating the acute effects of L-arginine on growth hormone and insulin release in mice.
abstract: l-arginine (l-Arg) rapidly stimulates GH and insulin release in vivo. It has been hypothesized that l-Arg stimulates GH release by lowering hypothalamic somatostatin (SST) tone. l-Arg may also act directly at the pituitary to stimulate GH release. Moreover, l-Arg has a direct stimulatory effect on β-cells, which is thought to be blunted by the release of SST from pancreatic δ-cells. To confirm the role of endogenous SST on l-Arg-induced GH and insulin release, wild-type (WT) and SST-knockout (SST-KO) mice were injected with l-Arg (ip; 0.8 g/kg), and pre-/post-injection GH, insulin, and glucose levels were measured. In WT mice, l-Arg evoked a 6-fold increase in circulating GH. However, there was only a modest increase in GH levels in WT pituitary cell cultures treated with l-Arg. In contrast, l-Arg failed to increase GH in SST-KO beyond their already elevated levels. These results further support the hypothesis that the primary mechanism by which l-Arg acutely increases GH in vivo is by lowering hypothalamic SST input to the pituitary and not via direct pituitary effects. Additionally, l-Arg induced a clear first-phase insulin secretion in WT mice, but not in SST-KO. However, SST-KO, but not WT mice, displayed a robust and sustained second-phase insulin release. These results further support a role for endogenous SST in regulating l-Arg-mediated insulin release.
authors.affiliation: Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, and Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutricion (CIBERobn), Córdoba 14014, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Córdoba-Chacón
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.forename: Ana I
authors.initials: AI
authors.lastname: Pozo-Salas
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D013004:Somatostatin; D013006:Growth Hormone; D001120:Arginine; D005947:Glucose