Cystic fibrosis transmembrane conductance regulator deficiency exacerbates islet cell dysfunction after beta-cell injury
Authors
Stalvey, Michael S.Mueller, Christian
Schatz, Desmond A.
Wasserfall, Clive H.
Campbell-Thompson, Martha L.
Theriaque, Douglas W.
Flotte, Terence R.
Atkinson, Mark A.
Document Type
Journal ArticlePublication Date
2006-07-29Keywords
Cystic FibrosisCystic Fibrosis Transmembrane Conductance Regulator
Diabetes Mellitus, Experimental
Inflammation
Islets of Langerhans
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Allergy and Immunology
Pediatrics
Respiratory Tract Diseases
Metadata
Show full item recordAbstract
The cause of cystic fibrosis-related diabetes (CFRD) remains unknown, but cystic fibrosis transmembrane conductance regulator (CFTR) mutations contribute directly to multiple aspects of the cystic fibrosis phenotype. We hypothesized that susceptibility to islet dysfunction in cystic fibrosis is determined by the lack of functional CFTR. To address this, glycemia was assessed in CFTR null (CFTR(-/-)), C57BL/6J, and FVB/NJ mice after streptozotocin (STZ)-induced beta-cell injury. Fasting blood glucose levels were similar among age-matched non-STZ-administered animals, but they were significantly higher in CFTR(-/-) mice 4 weeks after STZ administration (288.4 +/- 97.4, 168.4 +/- 35.9, and 188.0 +/- 42.3 mg/dl for CFTR(-/-), C57BL/6J, and FVB/NJ, respectively; P < 0.05). After intraperitoneal glucose administration, elevated blood glucose levels were also observed in STZ-administered CFTR(-/-) mice. STZ reduced islets among all strains; however, only CFTR(-/-) mice demonstrated a negative correlation between islet number and fasting blood glucose (P = 0.02). To determine whether a second alteration associated with cystic fibrosis (i.e., airway inflammation) could impact glucose control, animals were challenged with Aspergillus fumigatus. The A. fumigatus-sensitized CFTR(-/-) mice demonstrated similar fasting and stimulated glucose responses in comparison to nonsensitized animals. These studies suggest metabolic derangements in CFRD originate from an islet dysfunction inherent to the CFTR(-/-) state.Source
Diabetes. 2006 Jul;55(7):1939-45.
Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43855PubMed ID
16804061Notes
Christian Mueller is cited on this publication as Christian Muller. At the time of publication, Christian Mueller and Terence Flotte were not yet affiliated with the University of Massachusetts Medical School.