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http://purl.uniprot.org/citations/26409461http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26409461http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

It has been suggested that the transcription factor ARNT/HIF1β is critical for maintaining in vivo glucose homeostasis and pancreatic beta cell glucose-stimulated insulin secretion (GSIS). Our goal was to gain more insights into the metabolic defects seen after the loss of ARNT/HIF1β in beta cells.

Methods

The in vivo and in vitro consequences of the loss of ARNT/HIF1β were investigated in beta cell specific Arnt/Hif1β knockout mice (β-Arnt (fl/fl/Cre) mice).

Results

The only in vivo defects found in β-Arnt (fl/fl/Cre) mice were significant increases in the respiratory exchange ratio and in vivo carbohydrate oxidation, and a decrease in lipid oxidation. The mitochondrial oxygen consumption rate was unaltered in mouse β-Arnt (fl/fl/Cre) islets upon glucose stimulation. β-Arnt (fl/fl/Cre) islets had an impairment in the glucose-stimulated increase in Ca(2+) signalling and a reduced insulin secretory response to glucose in the presence of KCl and diazoxide. The glucose-stimulated increase in the NADPH/NADP(+) ratio was reduced in β-Arnt (fl/fl/Cre) islets. The reduced GSIS and NADPH/NADP(+) levels in β-Arnt (fl/fl/Cre) islets could be rescued by treatment with membrane-permeable tricarboxylic acid intermediates. Small interfering (si)RNA mediated knockdown of ARNT/HIF1β in human islets also inhibited GSIS. These results suggest that the regulation of GSIS by the KATP channel-dependent and -independent pathways is affected by the loss of ARNT/HIF1β in islets.

Conclusions/interpretation

This study provides three new insights into the role of ARNT/HIF1β in beta cells: (1) ARNT/HIF1β deletion in mice impairs GSIS ex vivo; (2) β-Arnt (fl/fl/Cre) mice have an increased respiratory exchange ratio; and (3) ARNT/HIF1β is required for GSIS in human islets."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.org/dc/terms/identifier"doi:10.1007/s00125-015-3768-4"xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Paglialunga S."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Huang M."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Gonzalez F.J."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Pillai R."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Bombardier E."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Tupling A.R."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Wheeler M.B."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Joseph J.W."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Prentice K.J."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Hoang M."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/author"Cousteils K."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/pages"2832-2842"xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/title"Deletion of ARNT/HIF1beta in pancreatic beta cells does not impair glucose homeostasis in mice, but is associated with defective glucose sensing ex vivo."xsd:string
http://purl.uniprot.org/citations/26409461http://purl.uniprot.org/core/volume"58"xsd:string
http://purl.uniprot.org/citations/26409461http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26409461
http://purl.uniprot.org/citations/26409461http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26409461
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