en
Scientific article
English

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

Published inAmerican journal of physiology: endocrinology and metabolism, vol. 291, no. 1, p. E50-58
Publication date2006
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 beta-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, -3alpha, and -3beta, 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 beta-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 beta-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.

Keywords
  • Animals
  • Blotting, Northern
  • Crosses, Genetic
  • Diabetes Mellitus, Experimental/ genetics/metabolism/pathology
  • Diabetes Mellitus, Type 1/ genetics/metabolism/pathology
  • Female
  • Gene Expression Regulation
  • Immunohistochemistry
  • Insulin-Like Growth Factor I/ deficiency/genetics
  • Islets of Langerhans/ metabolism/pathology
  • Lithostathine/biosynthesis/ genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger/biosynthesis/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
Citation (ISO format)
LU, Yarong et al. Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas. In: American journal of physiology: endocrinology and metabolism, 2006, vol. 291, n° 1, p. E50–58. doi: 10.1152/ajpendo.00596.2005
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ISSN of the journal0193-1849
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