SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

X. P. Wang, J. Yang, M. A. Norman, J. Magnusson, F. J. DeMayo, F. C. Brunicardi

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (βSSTR5 Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, βSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the βSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in βSSTR5Kd mice pancreata. In addition, βSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in βSSTR5Kd mice. Further studies of βSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.

Original languageEnglish (US)
Pages (from-to)3107-3114
Number of pages8
JournalFEBS Letters
Issue number14
StatePublished - Jun 6 2005
Externally publishedYes


  • Beta-cell specific knockdown
  • G-protein
  • Global knockout

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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