PKCepsilon mediates glucose-regulated insulin production in pancreatic beta-cells
| Autor: | Erol Cerasi, Avital Dov, Rafael Nesher, Eva Abramovitch, Marina Jmoudiak, Nasim Warwar, Ren Wu, Esther Haber |
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| Rok vydání: | 2008 |
| Předmět: |
Male
endocrine system medicine.medical_specialty medicine.medical_treatment Prohormone Enteroendocrine cell Protein Kinase C-epsilon Biology Gene Expression Regulation Enzymologic Insulin-Secreting Cells Internal medicine Insulin Secretion medicine Animals Insulin Rats Wistar Molecular Biology Cells Cultured Proinsulin chemistry.chemical_classification geography geography.geographical_feature_category Base Sequence Binding protein β′COP1 Cell Biology Transfection Islet Rats Enzyme Activation Translocation inhibiting peptides Proinsulin biosynthesis Protein Transport Glucose Endocrinology Enzyme chemistry siRNA Anchoring proteins Signal Transduction medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783:1929-1934 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2008.04.007 |
| Popis: | Endocrine cells produce large amounts of one or more peptides. The post-translational control of selective production of a single protein is often unknown. We used 3 unrelated approaches to diminish PKCepsilon in rat islets to evaluate its role in preferential glucose-mediated insulin production. Transfection with siRNA (siR-PKCepsilon) or expression of inactive PKCepsilon (PKCepsilon-KD) resulted in a significant reduction in insulin response to glucose (16.7 mmol/l). Glucose stimulation resulted in concentration of PKCepsilon in the perinuclear region, an area known to be rich in ER-Golgi systems, associated with insulin-containing structures. ss'COP1 (RACK2) is the anchoring protein for PKCepsilon. Glucose-stimulated proinsulin production was diminished by 50% in islets expressing PKCepsilon-KD, and 60% in islets expressing RACK2 binding protein (epsilonV1-2); total protein biosynthesis was not affected. In islets expressing epsilonV1-2, a chase period following glucose stimulus resulted in a reduced proinsulin conversion to mature insulin. We propose that PKCepsilon plays a specific role in mediating the glucose-signal into insulin production: binding to ss'COP1 localizes the activated enzyme to the RER where it modulates the shuttling of proinsulin to the TGN. Subsequently the enzyme may be involved in anterograde trafficking of the prohormone or in its processing within the TGN. |
| Databáze: | OpenAIRE |
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