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Cystic fibrosis transmembrane conductance regulator deficiency exacerbates islet cell dysfunction after beta-cell injury.
Stalvey, Michael S; Muller, Christian; Schatz, Desmond A; Wasserfall, Clive H; Campbell-Thompson, Martha L; Theriaque, Douglas W; Flotte, Terence R; Atkinson, Mark A.
Afiliação
  • Stalvey MS; Department of Pathology, University of Florida, College of Medicine, PO Box 100275, Gainesville, FL 32610, USA.
Diabetes ; 55(7): 1939-45, 2006 Jul.
Article em En | MEDLINE | ID: mdl-16804061
ABSTRACT
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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhotas Pancreáticas / Regulador de Condutância Transmembrana em Fibrose Cística Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Diabetes Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhotas Pancreáticas / Regulador de Condutância Transmembrana em Fibrose Cística Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Diabetes Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Estados Unidos