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β cell expression of IGF-I leads to recovery from type 1 diabetes
Mónica George, … , Jean Christophe Devedjian, Fatima Bosch
Mónica George, … , Jean Christophe Devedjian, Fatima Bosch
Published May 1, 2002
Citation Information: J Clin Invest. 2002;109(9):1153-1163. https://doi.org/10.1172/JCI12969.
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Article Endocrinology

β cell expression of IGF-I leads to recovery from type 1 diabetes

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Abstract

Patients with type 1 diabetes are identified after the onset of the disease, when β cell destruction is almost complete. β cell regeneration from islet cell precursors might reverse this disease, but factors that can induce β cell neogenesis and replication and prevent a new round of autoimmune destruction remain to be identified. Here we show that expression of IGF-I in β cells of transgenic mice (in both C57BL/6–SJL and CD-1 genetic backgrounds) counteracts cytotoxicity and insulitis after treatment with multiple low doses of streptozotocin (STZ). STZ-treated nontransgenic mice developed high hyperglycemia and hypoinsulinemia, lost body weight, and died. In contrast, STZ-treated C57BL/6–SJL transgenic mice showed mild hyperglycemia for about 1 month, after which they normalized glycemia and survived. After STZ treatment, all CD-1 mice developed high hyperglycemia, hypoinsulinemia, polydipsia, and polyphagia. However, STZ-treated CD-1 transgenic mice gradually normalized all metabolic parameters and survived. β cell mass increased in parallel as a result of neogenesis and β cell replication. Thus, our results indicate that local expression of IGF-I in β cells regenerates pancreatic islets and counteracts type 1 diabetes, suggesting that IGF-I gene transfer to the pancreas might be a suitable therapy for this disease.

Authors

Mónica George, Eduard Ayuso, Alba Casellas, Cristina Costa, Jean Christophe Devedjian, Fatima Bosch

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Figure 1

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Expression of IGF-I and insulin in the pancreas of transgenic mice (C57B...
Expression of IGF-I and insulin in the pancreas of transgenic mice (C57BL/6–SJL genetic background). Total cellular RNA was obtained from nontransgenic (Con) and transgenic (Tg) mice and analyzed by Northern blot as indicated in Methods. Two transcripts were detected in the pancreas of transgenic mice when hybridized with IGF-I probe. The 0.8-kb transcript came from the expression of the endogenous gene, and the 1.2-kb transcript came from the expression of the transgene and was polyadenylated at the end of the β-globin gene.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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