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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/E50    most recent 00596.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Lu, Y. Articles by Liu, J.-L. Search for Related Content PubMed PubMed Citation Articles by Lu, Y. Articles by Liu, J.-L.

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

Fraser Laboratories for Diabetes Research, Department of Medicine, and ¹McGill University and Genome Québec Innovation Centre, McGill University, Montreal, Quebec, Canada; ²Department of Advanced Biological Sciences for Regeneration and ³Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai Miyagi, Japan; and ⁴Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland

Submitted 30 November 2005 ; accepted in final form 26 January 2006

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 -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, -3, and -3, 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 -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 -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.

pancreatic islets; DNA microarray; gene-targeted mice; insulin-like growth factor I

This article has been cited by other articles:

				K. Robertson, Y. Lu, K. De Jesus, B. Li, Q. Su, P. K. Lund, and J.-L. Liu A general and islet cell-enriched overexpression of IGF-I results in normal islet cell growth, hypoglycemia, and significant resistance to experimental diabetes Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E928 - E938. [Abstract] [Full Text] [PDF]