Proinsulin processing in the diabetic Goto-Kakizaki rat
Autor: | John C. Hutton, D. J. Gross, Vincent Poitout, Rodabe N Amaria, Claes-Göran Östenson, S. M. Abdel-Halim, Paul C. Guest, A. Clark |
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Rok vydání: | 2002 |
Předmět: |
endocrine system
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Blotting Western Proprotein convertase 2 Nerve Tissue Proteins Carboxypeptidases Neuroendocrine Secretory Protein 7B2 Endocrinology Western blot Internal medicine medicine Animals Aspartic Acid Endopeptidases Subtilisins Protein Precursors Rats Wistar Pancreas Proinsulin geography geography.geographical_feature_category biology medicine.diagnostic_test Insulin Neuropeptides Chromogranin A Carboxypeptidase H Rats Inbred Strains Islet Immunohistochemistry Rats Blot Pituitary Hormones Proprotein Convertase 2 Carboxypeptidase E Diabetes Mellitus Type 2 Models Animal biology.protein Proprotein Convertases |
Zdroj: | The Journal of endocrinology. 175(3) |
ISSN: | 0022-0795 |
Popis: | The biosynthesis and processing of proinsulin was investigated in the diabetic Goto-Kakizaki (GK) rat. Immunofluorescence microscopy comparing GK and Wistar control rat pancreata revealed marked changes in the distribution of alpha-cells and pronounced beta-cell heterogeneity in the expression patterns of insulin, prohormone convertases PC1, PC2, carboxypeptidase E (CPE) and the PC-binding proteins 7B2 and ProSAAS. Western blot analyses of isolated islets revealed little difference in PC1 and CPE expression but PC2 immunoreactivity was markedly lower in the GK islets. The processing of the PC2-dependent substrate chromogranin A was reduced as evidenced by the appearance of intermediates. No differences were seen in the biosynthesis and post-translational modification of PC1, PC2 or CPE following incubation of islets in 16.7 mM glucose, but incubation in 3.3 mM glucose resulted in decreased PC2 biosynthesis in the GK islets. The rates of biosynthesis, processing and secretion of newly synthesized (pro)insulin were comparable. Circulating insulin immunoreactivity in both Wistar and GK rats was predominantly insulin 1 and 2 in the expected ratios with no (pro)insulin evident. Thus, the marked changes in islet morphology and PC2 expression did not impact the rate or extent of proinsulin processing either in vitro or in vivo in this experimental model. |
Databáze: | OpenAIRE |
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