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Research Article Free access | 10.1172/JCI118278

Potent inhibitory effects of transplantable rat glucagonomas and insulinomas on the respective endogenous islet cells are associated with pancreatic apoptosis.

N Blume, J Skouv, L I Larsson, J J Holst, and O D Madsen

Hagedorn Research Institute, Gentofte, Denmark.

Find articles by Blume, N. in: PubMed | Google Scholar

Hagedorn Research Institute, Gentofte, Denmark.

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Hagedorn Research Institute, Gentofte, Denmark.

Find articles by Larsson, L. in: PubMed | Google Scholar

Hagedorn Research Institute, Gentofte, Denmark.

Find articles by Holst, J. in: PubMed | Google Scholar

Hagedorn Research Institute, Gentofte, Denmark.

Find articles by Madsen, O. in: PubMed | Google Scholar

Published November 1, 1995 - More info

Published in Volume 96, Issue 5 on November 1, 1995
J Clin Invest. 1995;96(5):2227–2235. https://doi.org/10.1172/JCI118278.
© 1995 The American Society for Clinical Investigation
Published November 1, 1995 - Version history
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Abstract

Effects of transplantable rat insulinomas (IN) and glucagonomas (GLU) on the endogenous pancreas were analyzed using morphometry, immunocytochemistry, in situ hybridization, and staining for apoptotic cells. Hyperinsulinemia (IN-rats) and hyper-GLP-1/glucagonemia (GLU-rats) were both associated with marked islet atrophy (67 and 76% of control average planimetrical islet area, respectively). Selective islet B cell inhibition of proinsulin (I and II) genes as well as of expression of the insulin gene transcription factor, IPF1/STF1, was found in IN-rats. Moreover, these islets were characterized by significant B cells apoptosis in the absence of infiltrating lymphocytes. In GLU-rats selective islet A cell inhibition was observed at the level of glucagon mRNA. These islets contained small, highly condensed but clearly active B cells with prominent IPF1/STF1-positive nuclei, surrounded by densely packed glucagon-negative cells with reduced cytoplasm. Furthermore, an active apoptotic process was found exclusively in the exocrine pancreas of GLU-rats. Thus, in IN-rats, islet B cell mass reduction is distinguished by non-immune-mediated programmed cell death, while GLU-rats exhibit A cell mass reduction by cytoplasmic retraction and selective exocrine apoptosis.

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