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

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.

• Authors: Yarong Lu, André Ponton, Hiroshi Okamoto, Shin Takasawa, Pedro L Herrera, Jun-Li Liu
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 291 Issue 1 Pg. E50-8 (Jul 2006) ISSN: 0193-1849 [Print] United States
• PMID: 16449294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lithostathine
• Pancreatitis-Associated Proteins
• REG3A protein, human
• RNA, Messenger
• Reg1 protein, mouse
• Insulin-Like Growth Factor I

Topics

• 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
• Pancreatitis-Associated Proteins
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction