Pancreatic β-cells are able to repair themselves after some sublethal injuries in vitro. However, little is known of the nature of the repair mechanisms active in these cells. This study examined the expression of growth arrest and DNA damage–inducible genes gadd 153 and gadd 45 in pancreatic rat islets and in the clonal insulin secretory HIT-T15 cells. Rat pancreatic islets were exposed in vitro to the alkylating agents streptozocin or methyl methanesulfonate, or to the cytokine recombinant interleukin-1 β. Islet exposure to STZ or MMS reduced insulin release by 40–50% over the next 4 h, whereas exposure to rIL-1 β induced a 60% increase in insulin release over the same period. Both gadd 153 and gadd 45 mRNA were detectable in rat islets, and their levels were increased twofold after STZ exposure, whereas MMS induced a fivefold increase in gadd 153 and a twofold increase in gadd 45 mRNA. Islet exposure to rIL-1β did not affect the expression of gadd 153 or gadd 45. HIT cells exposed to STZ or MMS also exhibited an increased expression of both gadd 153 and gadd 45. Again, this increase in gadd mRNA was more marked after MMS exposure. Moreover, expression of both gadd 153 and gadd 45 after MMS exposure lasted for a longer period of time than after STZ treatment. The effects of MMS on the expression of both gadd genes were inhibited by actinomycin D, suggesting that transcription is necessary for acute gadd induction. As a whole, these data show that gadd 153 and gadd 45 are increased in pancreatic islets or HIT cells after exposure to alkylating agents. Gadd expression may be related to cellular adaptation or DNA repair or both after stress. Because islets are able to recover completely their function after MMS exposure but not after STZ exposure, the role of these gadd genes may be relevant in the repair of islet DNA damage.
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Original Articles|
May 01 1993
Genotoxic Agents Increase Expression of Growth Arrest and DNA Damage–Inducible Genes gadd 153 and gadd 45 in Rat Pancreatic Islets
Decio L Eizirik;
Decio L Eizirik
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School
Boston, Massachusetts
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Andreas Björklund;
Andreas Björklund
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School
Boston, Massachusetts
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Enrico Cagliero
Enrico Cagliero
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School
Boston, Massachusetts
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Address correspondence and reprint requests to Dr. Décio L. Eizirik, Department of Medical Cell Biology, BMC, Uppsala University, Box 571, S-751 23, Uppsala, Sweden.
Diabetes 1993;42(5):738–745
Article history
Received:
June 25 1992
Revision Received:
December 17 1992
Accepted:
December 17 1992
PubMed:
8482431
Citation
Decio L Eizirik, Andreas Björklund, Enrico Cagliero; Genotoxic Agents Increase Expression of Growth Arrest and DNA Damage–Inducible Genes gadd 153 and gadd 45 in Rat Pancreatic Islets. Diabetes 1 May 1993; 42 (5): 738–745. https://doi.org/10.2337/diab.42.5.738
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