beta-endorphin and Adenoma--Islet-Cell

Pancreatic tissue from 3 cases of hyperinsulinemic hypoglycemia was examined using histochemical and immunoperoxidase staining techniques. The insular lesions present were adenomatosis and insulin-producing islet-cell adenomata. The great majority of the islet parenchymal cells in these lesions were reactive with antibodies to pro-insulin, C-peptide, and insulin. A variable number of islet cells was found to react with beta-endorphin antiserum in all 3 cases, while the reaction with antiserum against the neural tissue marker antigen, S-100, was restricted to the cases with islet-cell adenoma. Argyrophil parenchymal cells were present in focal adenomatosis but almost absent in insulomata. These results suggest that various lesions of the endocrine pancreas causing hypoglycemia can be distinguished by means of specific histo- and immunocytochemical methods because of differences in the distribution of characteristic cellular antigens.

Topics: Adenoma; Adenoma, Islet Cell; Adolescent; Adult; beta-Endorphin; Child; Child, Preschool; Female; Humans; Hypoglycemia; Immunoenzyme Techniques; Immunohistochemistry; Infant; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Radioimmunoassay

Proopiomelanocortin (POMC) is a neuroendocrine precursor protein which is processed at paired basic amino acids in a tissue-specific manner. To study this phenomenon, a vaccinia virus recombinant, which directs the synthesis of mouse POMC (VV:mPOMC) was constructed and used to infect epithelial (BSC-40) and endocrine (Rin m5F) cell lines. Bona fide mPOMC was produced in both cell types and beta-endorphin immunoreactivity was secreted in a nonregulated manner from BSC-40 cells and in a regulated manner from Rin m5F cells. Although the precursor was not cleaved to smaller beta-MSH or beta-endorphin immunoreactive peptides in BSC-40 cell extracts, Rin m5F cells produced primarily authentic gamma-lipotropin and des-acetyl beta-endorphin. Furthermore, production of these peptides was restricted to the regulated secretory pathway in Rin m5F cells. Site-directed mutagenesis was then used to change the inefficiently recognized Lys-Lys potential cleavage site near the carboxyl terminus of beta-endorphin to Lys-Arg. Expression of the mutant precursor in Rin m5F cells resulted in the synthesis of both des-acetyl beta-endorphin and beta-endorphin.

Topics: Adenoma, Islet Cell; Amino Acid Sequence; Animals; Base Sequence; beta-Endorphin; beta-Lipotropin; Chromatography, High Pressure Liquid; DNA, Recombinant; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation; Insulinoma; Melanocyte-Stimulating Hormones; Mice; Molecular Sequence Data; Mutation; Pancreatic Neoplasms; Pro-Opiomelanocortin; Transfection; Tumor Cells, Cultured; Vaccinia virus