2016
DOI: 10.1152/ajpendo.00333.2015
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CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response

Abstract: Cystic fibrosis (CF)-related diabetes (CFRD) has become a critical complication that seriously affects the clinical outcomes of CF patients. Although CFRD has emerged as the most common nonpulmonary complication of CF, little is known about its etiopathogenesis. Additionally, whether oxidative stress (OxS), a common feature of CF and diabetes, influences CFRD pathophysiology requires clarification. The main objective of this study was to shed light on the role of the cystic fibrosis transmembrane conductance r… Show more

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Cited by 54 publications
(51 citation statements)
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“…Studies of CFTR in islet cell lines (12,14,16), ferret/rodent islets (11-13, 15, 16, 20, 25, 35), human islets (11,15), and CF patients (18,21,22,24,(26)(27)(28)52) have suggested that intrinsic dysregulation of α and β cell secretion and/or islet loss caused by pancreatic destruction contribute(s) to CFRD pathogenesis. Importantly, islet-intrinsic CFTR regulation of insulin and glucagon secretion by α and β cells would identify new mechanisms regulating islet hormone secretion and represent a targetable pathway for CFRD treatment.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Studies of CFTR in islet cell lines (12,14,16), ferret/rodent islets (11-13, 15, 16, 20, 25, 35), human islets (11,15), and CF patients (18,21,22,24,(26)(27)(28)52) have suggested that intrinsic dysregulation of α and β cell secretion and/or islet loss caused by pancreatic destruction contribute(s) to CFRD pathogenesis. Importantly, islet-intrinsic CFTR regulation of insulin and glucagon secretion by α and β cells would identify new mechanisms regulating islet hormone secretion and represent a targetable pathway for CFRD treatment.…”
Section: Discussionmentioning
confidence: 99%
“…Recently, loss of CFTR function in cell lines and cultured rodent/ferret and human islets has been reported to impair insulin secretion (11)(12)(13)(14) and augment glucagon secretion (15,16), suggesting that loss of CFTR function in islet endocrine cells contributes to CFRD via intrinsic disruption of β and α cell stimulus-secretion coupling. Conversely, studies of humans and CF animal models have suggested that CFRD results from CF-induced pancreatic autolysis, inflammation, and reduction of β cell mass (17)(18)(19)(20) causing insufficient islet hormone secretion (20)(21)(22)(23)(24)(25)(26)(27).…”
Section: Introductionmentioning
confidence: 99%
“…In 2007, Cftr mRNA and CFTR protein expression was first reported in primary rat islet β cells and RIN-5mF insulinoma cells, at levels lower than those in 'non-β cells' (Boom et al 2007). Subsequent studies confirmed that RIN-5mF and MIN6 cells both express detectable CFTR (Guo et al 2014, Ntimbane et al 2016. Isolated primary human β cells were reported to have immunoreactivity for CFTR, although mRNA data were not reported (Guo et al 2014).…”
Section: Islet Endocrine Cell Autonomous Actions Of Cftrmentioning
confidence: 99%
“…There is mounting evidence that mutant CF Transmembrane Conductance regulator (CFTR), the CF disease-causing gene, is expressed in islet cells and is associated with abnormal cell function [30,31]. Although, it is one of the critical factors in the development of CFRD, whether this defect, by itself, is sufficient for the development of CFRD is unlikely.…”
Section: Discussionmentioning
confidence: 99%