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.
Highlights
It is well documented that injection of the amino acid, L–arginine (L-Arg), rapidly increases circulating GH levels in a variety of species [1,2,3,4,5,6]
This stimulatory action of L-Arg is thought to be primarily mediated by suppressing hypothalamic somatostatin (SST) input to the pituitary somatotropes [1, 7]
In order to confirm the role of endogenous SST in regulating the stimulatory actions of L-Arg on GH and insulin release in vivo, the current study examined the acute effects of L-Arg on circulating GH and insulin levels in male and female SST-knockout (SST-KO) mice and their wildtype (WT) littermate controls
Summary
It is well documented that injection of the amino acid, L–arginine (L-Arg), rapidly increases circulating GH levels in a variety of species [1,2,3,4,5,6]. In order to confirm the role of endogenous SST in regulating the stimulatory actions of L-Arg on GH and insulin release in vivo, the current study examined the acute effects of L-Arg on circulating GH and insulin levels in male and female SST-knockout (SST-KO) mice and their wildtype (WT) littermate controls.
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