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Title

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

Authors
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
Identifiers
PMID: 16449294
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Structures
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. https://archive-ouverte.unige.ch/unige:8868

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Deposited on : 2010-07-12

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