Proglucagon processing similar to normal islets in pancreatic alpha-like cell line derived from transgenic mouse tumor

Powers, A. C., Efrat, S., Mojsov, S., Spector, D., Habener, J. F., Hanahan, D. (April 1990) Proglucagon processing similar to normal islets in pancreatic alpha-like cell line derived from transgenic mouse tumor. Diabetes, 39 (4). pp. 406-14. ISSN 0012-1797 (Print)0012-1797

DOI: 10.2337/diab.39.4.406


A pancreatic alpha-like cell line has been established from a glucagonoma arising in transgenic mice expressing a hybrid gene consisting of the rat glucagon-promoter sequence fused to the sequence encoding the SV40 T-antigen oncoprotein. The alpha-tumor cell 1 (alpha TC1) line maintained many characteristics of differentiated alpha-cells for greater than 40 passages in culture and expressed levels of glucagon mRNA 5- to 10-fold higher than those reported previously in rat and hamster islet cell lines. By radioimmunoassay, the cells synthesized considerable amounts of glucagon, glucagonlike peptide I (GLP-I), the major proglucagon fragment, and small amounts of unprocessed proglucagon but no free GLP-II. This distribution of peptides is similar to that found in extracts of rodent pancreases and is distinct from that seen with other islet cell lines, which process proglucagon in patterns more characteristic of intestinal cells. The GLP-I peptide in the alpha TC1 cell line was in the form of GLP-I-(1-37), which is inactive as a stimulator of insulin secretion, and not GLP-I-7-37) or -(7-36)-amide peptides, both of which are potent insulin secretagogues. The alpha TC1 cell line produced glucagon-related peptides in a relatively uniform pattern by immunocytochemistry, and electron microscopy revealed typical alpha-type (glucagon) secretory granules. Although the cell line was derived from an islet tumor producing only glucagon, the alpha TC1 cell line also produced insulin in addition to the glucagon peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Item Type: Paper
Uncontrolled Keywords: Adenoma, Islet Cell/*metabolism Animals Cell Line Chromatography, Gel Chromatography, High Pressure Liquid Glucagon/*genetics/secretion Glucagonoma/*metabolism/pathology/ultrastructure Insulin/genetics Islets of Langerhans/*metabolism/pathology Mice Mice, Transgenic Pancreatic Neoplasms/*metabolism/pathology/ultrastructure Proglucagon Protein Precursors/*genetics *Protein Processing, Post-Translational RNA, Messenger/genetics RNA, Neoplasm/genetics/isolation & purification Tumor Cells, Cultured/metabolism
Subjects: diseases & disorders > nutritional and metabolic diseases > diabetes
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Spector lab
Depositing User: Matt Covey
Date: April 1990
Date Deposited: 26 Mar 2014 20:15
Last Modified: 23 Jan 2015 20:11
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