Morphological and functional adaptation of pancreatic islet blood vessels to insulin resistance is impaired in diabetic db/db mice.
Biochim Biophys Acta Mol Basis Dis
; 1868(4): 166339, 2022 04 01.
Article
em En
| MEDLINE
| ID: mdl-35017029
ABSTRACT
The pancreatic islet vasculature is of fundamental importance to the ß-cell response to obesity-associated insulin resistance. To explore islet vascular alterations in the pathogenesis of type 2 diabetes, we evaluated two insulin resistance models ob/ob mice, which sustain large ß-cell mass and hyperinsulinemia, and db/db mice, which progress to diabetes due to secondary ß-cell compensation failure for insulin secretion. Time-dependent changes in islet vasculature and blood flow were investigated using tomato lectin staining and in vivo live imaging. Marked islet capillary dilation was observed in ob/ob mice, but this adaptive change was blunted in db/db mice. Islet blood flow volume was augmented in ob/ob mice, whereas it was reduced in db/db mice. The protein concentrations of total and phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 were increased in ob/ob islets, while they were diminished in db/db mice, indicating decreased eNOS activity. This was accompanied by an increased retention of advanced glycation end-products in db/db blood vessels. Amelioration of diabetes by Elovl6 deficiency involved a restoration of capillary dilation, blood flow, and eNOS phosphorylation in db/db islets. Our findings suggest that the disability of islet capillary dilation due to endothelial dysfunction impairs local islet blood flow, which may play a role in the loss of ß-cell function and further exacerbate type 2 diabetes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasos Sanguíneos
/
Ilhotas Pancreáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Ano de publicação:
2022
Tipo de documento:
Article