Chromogranin A regulates vesicle storage and mitochondrial dynamics to influence insulin secretion
Autor: | Lee E. Eiden, Sumana Mahata, Angelo Corti, Angelina Hernandez-Carretero, Sushil K. Mahata, Joshua Wollam, Angshuman Biswas, Nicholas J. G. Webster, Matthew Riopel, Nai-Wen Chi, Nitish R. Mahapatra, Gautam Bandyopadhyay |
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Přispěvatelé: | Wollam, Joshua, Mahata, Sumana, Riopel, Matthew, Hernandez Carretero, Angelina, Biswas, Angshuman, Bandyopadhyay, Gautam K., Chi, Nai Wen, Eiden, Lee E., Mahapatra, Nitish R., Corti, Angelo, Webster, Nicholas J. G., Mahata, Sushil K. |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male endocrine system medicine.medical_specialty Histology medicine.medical_treatment Biology Mitochondrion Mitochondrial Dynamics Exocytosis Pathology and Forensic Medicine 03 medical and health sciences Islets of Langerhans Mice Dense core vesicle Internal medicine Insulin Secretion medicine Animals Insulin Pancreastatin Pancreatic islets Secretory Vesicles Chromogranin A Cell Differentiation Cell Biology Glucagon Secretory Vesicle Peptide Fragments Mitochondria Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Glucose mitochondrial fusion Gene Expression Regulation biology.protein Pancreas Catestatin Somatostatin Calreticulin |
Zdroj: | Cell and tissue research. 368(3) |
ISSN: | 1432-0878 |
Popis: | Chromogranin A (CgA) is a prohormone and a granulogenic factor that regulates secretory pathways in neuroendocrine tissues. In β-cells of the endocrine pancreas, CgA is a major cargo in insulin secretory vesicles. The impact of CgA deficiency on the formation and exocytosis of insulin vesicles is yet to be investigated. In addition, no literature exists on the impact of CgA on mitochondrial function in β-cells. Using three different antibodies, we demonstrate that CgA is processed to vasostatin- and catestatin-containing fragments in pancreatic islet cells. CgA deficiency in Chga-KO islets leads to compensatory overexpression of chromogranin B, secretogranin II, SNARE proteins and insulin genes, as well as increased insulin protein content. Ultrastructural studies of pancreatic islets revealed that Chga-KO β-cells contain fewer immature secretory granules than wild-type (WT) control but increased numbers of mature secretory granules and plasma membrane-docked vesicles. Compared to WT control, CgA-deficient β-cells exhibited increases in mitochondrial volume, numerical densities and fusion, as well as increased expression of nuclear encoded genes (Ndufa9, Ndufs8, Cyc1 and Atp5o). These changes in secretory vesicles and the mitochondria likely contribute to the increased glucose-stimulated insulin secretion observed in Chga-KO mice. We conclude that CgA is an important regulator for coordination of mitochondrial dynamics, secretory vesicular quanta and GSIS for optimal secretory functioning of β-cells, suggesting a strong, CgA-dependent positive link between mitochondrial fusion and GSIS. |
Databáze: | OpenAIRE |
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