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Progressive change of intra‐islet GLP‐1 production during diabetes development
Author(s) -
O'Malley Thomas J.,
Fava Genevieve E.,
Zhang Yanqing,
Fonseca Vivian A.,
Wu Hongju
Publication year - 2014
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2534
Subject(s) - islet , proglucagon , medicine , glucagon , endocrinology , diabetes mellitus , downregulation and upregulation , type 2 diabetes , pancreatic islets , type 1 diabetes , glucagon like peptide 1 , insulin , biology , gene , biochemistry
Background Glucagon‐like peptide 1 (GLP‐1) and glucagon share the same precursor molecule proglucagon, but each arises from a distinct posttranslational process in a tissue‐specific manner. Recently, it has been shown that GLP‐1 is co‐expressed with glucagon in pancreatic islet cells. This study was aimed to investigate the progressive changes of GLP‐1 versus glucagon production in pancreatic islets during the course of diabetes development. Methods Both type 1 (non‐obese diabetes mice) and type 2 (db/db mice) diabetes models were employed in this study. The mice were monitored closely for their diabetes progression and were sacrificed at different stages according to their blood glucose levels. GLP‐1 and glucagon expression in the pancreatic islets was examined using immunohistochemistry assays. Quantitative analysis was performed to evaluate the significance of the changes. Results The ratio of GLP‐1‐expressing cells to glucagon‐expressing cells in the islets showed significant, progressive increase with the development of diabetes in db/db mice. The increase of GLP‐1 expression was in agreement with the upregulation of PC1/3 expression in these cells. Interestingly, intra‐islet GLP‐1 expression was not significantly changed during the development of type 1 diabetes in non‐obese diabetes mice. Conclusions The study demonstrated that GLP‐1 was progressively upregulated in pancreatic islets during type 2 diabetes development. In addition, the data suggest clear differences in intra‐islet GLP‐1 production between type 1 and type 2 diabetes developments. These differences may have an effect on the clinical and pathophysiological processes of these diseases and may be a target for therapeutic approaches. Copyright © 2014 John Wiley & Sons, Ltd.