Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas.
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.
Lu
Yarong
Y
Fraser Laboratories, Rm. M3-15, Royal Victoria Hospital, 687 Pine Ave. West, Montreal, QC H3A 1A1, Canada.
Ponton
André
A
Okamoto
Hiroshi
H
Takasawa
Shin
S
Herrera
Pedro L
PL
Liu
Jun-Li
JL
D000818:Animals; D015152:Blotting, Northern; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051847:Lithostathine / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051847:Lithostathine; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C497615:Reg1 protein, mouse; D007334:Insulin-Like Growth Factor I