Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas

Yarong Lu, André Ponton, Hiroshi Okamoto, Shin Takasawa, Pedro L. Herrera, Jun Li Liu

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

We have recently reported that Pdx1-Cre-mediated whole pancreas inactivation of IGF-I gene [in pancreatic-specific IGF-I gene-deficient (PID) mice] results in increased β-cell mass and significant protection against both type 1 and type 2 diabetes. Because the phenotype is unlikely a direct consequence of IGF-I deficiency, the present study was designed to explore possible activation of proislet factors in PID mice by using a whole genome DNA microarray. As a result, multiple members of the Reg family genes (Reg2, -3α, and -3β, previously not known to promote islet cell growth) were significantly upregulated in the pancreas. This finding was subsequently confirmed by Northern blot and/or real-time PCR, which exhibited 2- to 8-fold increases in the levels of these mRNAs. Interestingly, these Reg family genes were also activated after streptozotocin-induced β-cell damage and diabetes (wild-type T1D mice) when islet cells were undergoing regeneration. Immunohistochemistry revealed increased Reg proteins in exocrine as well as endocrine pancreas and suggested their potential role in β-cell neogenesis in PID or T1D mice. Previously, other Reg proteins (Reg1 and islet neogenesis-associated protein) have been shown to promote islet cell replication and neogenesis. These uncharacterized Reg proteins may play a similar but more potent role, not only in normal islet cell growth in PID mice, but also in islet cell regeneration after T1D.

Original languageEnglish
Pages (from-to)E50-E58
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume291
Issue number1
DOIs
Publication statusPublished - 2006

Keywords

  • DNA microarray
  • Gene-targeted mice
  • Insulin-like growth factor I
  • Pancreatic islets

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas'. Together they form a unique fingerprint.

Cite this