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

Lu, Yarong
Ponton, Andre
Okamoto, Hiroshi
Takasawa, Shin
Liu, J. L.
Published in American journal of physiology: endocrinology and metabolism. 2006, vol. 291, no. 1, p. E50-58
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 AnimalsBlotting, NorthernCrosses, GeneticDiabetes Mellitus, Experimental/ genetics/metabolism/pathologyDiabetes Mellitus, Type 1/ genetics/metabolism/pathologyFemaleGene Expression RegulationImmunohistochemistryInsulin-Like Growth Factor I/ deficiency/geneticsIslets of Langerhans/ metabolism/pathologyLithostathine/biosynthesis/ geneticsMaleMiceMice, Inbred C57BLMice, Inbred DBAMice, TransgenicOligonucleotide Array Sequence AnalysisRNA, Messenger/biosynthesis/geneticsReverse Transcriptase Polymerase Chain Reaction
PMID: 16449294
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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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 https://archive-ouverte.unige.ch/unige:8868

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Deposited on : 2010-07-12

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