Cystic fibrosis‐related diabetes compared with type 1 and type 2 diabetes in adults

Konrad, Katja; Scheuing, Nicole; Badenhoop, Klaus; Borkenstein, Martin; Gohlke, Bettina; Schöfl, Christof; Seufert, Jochen; Thon, A.; Holl, Reinhard W.

doi:10.1002/dmrr.2429

Cited by 45 publications

(32 citation statements)

References 30 publications

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“…Importantly, CFRD exacerbates CF-related complications and is associated with increased mortality (2,3). CFRD is recognized as a form of type 3c (pancreatogenic) diabetes but is often regarded as a distinct clinical entity (2,4), as CFRD displays features of both type 1 diabetes (T1D) and type 2 diabetes (T2D) that occur in the setting of pancreatic insufficiency, multiorgan dysfunction, chronic infection, malabsorption, malnutrition, and varying degrees of insulin resistance (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Cystic fibrosis–related diabetes is caused by islet loss and inflammation

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Cystic fibrosis–related diabetes is caused by islet loss and inflammation

et al. 2018

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“…[22][23][24][25] The most lethal clinical manifestation of CF is lung disease, with chronic inflammation and infection causing damage to the organ with deteriorating lung function. 22 Other clinical manifestations of CF include CF-related diabetes, 26,27 liver disease, gall bladder disease, intestinal disease, bone disease 28 and abnormalities in fatty acid metabolism. 29 However, the molecular mechanisms underlying the pathogenesis of these CF-related diseases remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Emerging role of cystic fibrosis transmembrane conductance regulator as an epigenetic regulator: linking environmental cues to microRNAs

Chan

Jiang

Ruan

2014

Clin Exp Pharma Physio

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SUMMARYAlthough microRNAs (miRNAs) have been recognized as one of the important epigenetic mechanisms that regulate gene expression in response to changes in the environment, the links between environmental cues and changes in miRNAs remain largely unknown. Localized to the cell membrane and recognized as an anion channel, the cystic fibrosis transmembrane conductance regulator (CFTR) has recently been shown to mediate important signalling pathways leading to activation of miRNAs. This brief review summarizes the related findings and discusses the emerging role of CFTR as an epigenetic regulator, possibly involved in a wide spectrum of physiological and pathological processes.

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“…Although the cause of insulin insufficiency is generally considered to be a result of β-cell damage by autoimmunity, a high percentage of diabetic patients with insulin insufficiency show negative of those autoantibodies3. Notably, whereas most CFRD cases exhibit insulin insufficiency45, the exact cause remains elusive although destruction of the insulin-secreting pancreatic islets secondary to the obstruction of the pancreatic duct due to defective CFTR has long been considered the underlying cause67. Interestingly, CFTR expression in the pancreatic islet has been reported8; however, its exact role in islet function remains unexplored.…”

mentioning

confidence: 99%

Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR

et al. 2014

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The cause of insulin insufficiency remains unknown in many diabetic cases. Up to 50% adult patients with cystic fibrosis (CF), a disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), develop CF-related diabetes (CFRD) with most patients exhibiting insulin insufficiency. Here we show that CFTR is a regulator of glucose-dependent electrical acitivities and insulin secretion in β-cells. We demonstrate that glucose elicited whole-cell currents, membrane depolarization, electrical bursts or action potentials, Ca2+ oscillations and insulin secretion are abolished or reduced by inhibitors or knockdown of CFTR in primary mouse β-cells or RINm5F β-cell line, or significantly attenuated in CFTR mutant (DF508) mice compared with wild-type mice. VX-809, a newly discovered corrector of DF508 mutation, successfully rescues the defects in DF508 β-cells. Our results reveal a role of CFTR in glucose-induced electrical activities and insulin secretion in β-cells, shed light on the pathogenesis of CFRD and possibly other idiopathic diabetes, and present a potential treatment strategy.

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Cystic fibrosis‐related diabetes compared with type 1 and type 2 diabetes in adults

Abstract: CFRD is a uniquely complex entity with clear differences from T1DM and T2DM in adults.

Cited by 45 publications

References 30 publications

Cystic fibrosis–related diabetes is caused by islet loss and inflammation

Cystic fibrosis–related diabetes is caused by islet loss and inflammation

Emerging role of cystic fibrosis transmembrane conductance regulator as an epigenetic regulator: linking environmental cues to microRNAs

Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR

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