Pancreatic somatostatin inhibits insulin secretion via SSTR-5 in the isolated perfused mouse pancreas model.
BACKGROUND
The function of pancreatic somatostatin in insulin secretion is controversial, and the receptor(s) mediating such event has not been exclusively investigated.


OBJECTIVE
To differentiate the specific role of SSTR5 in the mouse pancreas, we generated a mouse SSTR5 gene ablation model. Mice homozygous for the deletion (SSTR5-/-) and wild type (WT) littermate controls underwent whole pancreas perfusion to determine the effect of SSTR5 gene ablation on glucose-stimulated insulin secretion. The perfusion was done with and without octreotide added to the infusion buffer. Furthermore, pancreatic somatostatin was immunoneutralized by using a potent somatostatin monoclonal antibody to determine whether pancreatic somatostatin regulates insulin secretion in these mice.


RESULTS
Results showed that at 3 months of age, there were no alterations in insulin secretion compared with WT controls. However, glucose-stimulated insulin secretion was significantly enhanced in 12-month-old SSTR5-/- mice compared with WT controls. The addition of octreotide to the perfusion significantly suppressed insulin secretion in WT controls, while it had no effect on SSTR5-/- mice. Immunoneutralization of pancreatic somatostatin resulted in enhanced glucose-stimulated insulin secretion in WT controls, but decreased levels of insulin secretion in SSTR5-/- mice.


CONCLUSIONS
These results suggest that, in the mouse, pancreatic somatostatin regulates insulin secretion through SSTR5, and that the effect is age-specific.
Tirone
T A
TA
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Norman
M A
MA
Moldovan
S
S
DeMayo
F J
FJ
Wang
X P
XP
Brunicardi
F C
FC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D018345:Mice, Knockout; D015282:Octreotide / Q000494:pharmacology; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013004:Somatostatin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007328:Insulin; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; D005947:Glucose; D015282:Octreotide