Defective secretion of islet hormones in chromogranin-B deficient mice.

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Defective secretion of islet hormones in chromogranin-B deficient mice. / Obermüller, Stefanie; Calegari, Federico; King, Angus; Lindqvist, Anders; Lundquist, Ingmar; Salehi, S Albert; Francolini, Maura; Rosa, Patrizia; Rorsman, Patrik; Huttner, Wieland B; Barg, Sebastian.

In: PLoS ONE, Vol. 5, No. 1, e8936, 2010.

Research output: Contribution to journalArticle

Harvard

Obermüller, S, Calegari, F, King, A, Lindqvist, A, Lundquist, I, Salehi, SA, Francolini, M, Rosa, P, Rorsman, P, Huttner, WB & Barg, S 2010, 'Defective secretion of islet hormones in chromogranin-B deficient mice.', PLoS ONE, vol. 5, no. 1, e8936. https://doi.org/10.1371/journal.pone.0008936

APA

Obermüller, S., Calegari, F., King, A., Lindqvist, A., Lundquist, I., Salehi, S. A., Francolini, M., Rosa, P., Rorsman, P., Huttner, W. B., & Barg, S. (2010). Defective secretion of islet hormones in chromogranin-B deficient mice. PLoS ONE, 5(1), [e8936]. https://doi.org/10.1371/journal.pone.0008936

CBE

Obermüller S, Calegari F, King A, Lindqvist A, Lundquist I, Salehi SA, Francolini M, Rosa P, Rorsman P, Huttner WB, Barg S. 2010. Defective secretion of islet hormones in chromogranin-B deficient mice. PLoS ONE. 5(1):Article e8936. https://doi.org/10.1371/journal.pone.0008936

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Author

Obermüller, Stefanie ; Calegari, Federico ; King, Angus ; Lindqvist, Anders ; Lundquist, Ingmar ; Salehi, S Albert ; Francolini, Maura ; Rosa, Patrizia ; Rorsman, Patrik ; Huttner, Wieland B ; Barg, Sebastian. / Defective secretion of islet hormones in chromogranin-B deficient mice. In: PLoS ONE. 2010 ; Vol. 5, No. 1.

RIS

TY - JOUR

T1 - Defective secretion of islet hormones in chromogranin-B deficient mice.

AU - Obermüller, Stefanie

AU - Calegari, Federico

AU - King, Angus

AU - Lindqvist, Anders

AU - Lundquist, Ingmar

AU - Salehi, S Albert

AU - Francolini, Maura

AU - Rosa, Patrizia

AU - Rorsman, Patrik

AU - Huttner, Wieland B

AU - Barg, Sebastian

PY - 2010

Y1 - 2010

N2 - Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined.

AB - Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined.

U2 - 10.1371/journal.pone.0008936

DO - 10.1371/journal.pone.0008936

M3 - Article

C2 - 20126668

VL - 5

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e8936

ER -