Tirone T A, Norman M A, Moldovan S, DeMayo F J, Wang X P, Brunicardi F C
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Pancreas. 2003 Apr;26(3):e67-73. doi: 10.1097/00006676-200304000-00025.
The function of pancreatic somatostatin in insulin secretion is controversial, and the receptor(s) mediating such event has not been exclusively investigated.
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 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.
These results suggest that, in the mouse, pancreatic somatostatin regulates insulin secretion through SSTR5, and that the effect is age-specific.
胰腺生长抑素在胰岛素分泌中的作用存在争议，介导该过程的受体尚未得到专门研究。
为了区分SSTR5在小鼠胰腺中的特定作用，我们构建了一个小鼠SSTR5基因敲除模型。对缺失纯合子（SSTR5-/-）小鼠和野生型（WT）同窝对照小鼠进行全胰腺灌注，以确定SSTR5基因敲除对葡萄糖刺激的胰岛素分泌的影响。灌注在添加和不添加奥曲肽的输注缓冲液中进行。此外，使用强效生长抑素单克隆抗体对胰腺生长抑素进行免疫中和，以确定胰腺生长抑素是否调节这些小鼠的胰岛素分泌。
结果显示，在3个月大时，与WT对照相比，胰岛素分泌没有变化。然而，与WT对照相比，12个月大的SSTR5-/-小鼠中葡萄糖刺激的胰岛素分泌显著增强。在灌注中添加奥曲肽可显著抑制WT对照中的胰岛素分泌，而对SSTR5-/-小鼠没有影响。胰腺生长抑素的免疫中和导致WT对照中葡萄糖刺激的胰岛素分泌增强，但SSTR5-/-小鼠中的胰岛素分泌水平降低。
这些结果表明，在小鼠中，胰腺生长抑素通过SSTR5调节胰岛素分泌，且这种作用具有年龄特异性。
