Noradrenergic fibers are associated with beta-cell dedifferentiation and impaired beta-cell function in humans
نویسندگان
چکیده
Aims/hypothesisType 2 diabetes (T2D) is characterized by a progressive loss of beta-cell function, and the “disappearance” beta-cells in T2D may also be caused process beta -cell dedifferentiation. Since noradrenergic innervation inhibits insulin secretion density fibers increased type mouse models, we aimed to study relation between islet innervation, dedifferentiation function humans.MethodsUsing immunohistochemistry electron microscopy, analyzed pancreata from organ donors patients undergoing pancreatic surgery. In latter, pre-surgical detailed metabolic characterization oral glucose tolerance test (OGTT) hyperglycemic clamp was performed before surgery, thus obtaining vivo functional parameters secretion.ResultsThe islets diabetic subjects were 3 times more innervated than controls (0.91 ± 0.21 vs 0.32 0.10, n.fibers/islet; p = 0.01), directly correlated with score (r 0.39; 0.03). secretion, assessed clamp, negatively increase [beta-cell Glucose Sensitivity −0.84; incremental second-phase −0.84, 0.03) arginine-stimulated −0.76, 0.04)]. Moreover, observed fibers, paralleling worsening (from NGT through IGT T2D).Conclusions/interpretationNoradrenergic are significantly this positively correlates score. The correlation suggests significant involvement these pathogenesis disease, indirectly, process.
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ژورنال
عنوان ژورنال: Metabolism-clinical and Experimental
سال: 2021
ISSN: ['0026-0495', '1532-8600']
DOI: https://doi.org/10.1016/j.metabol.2020.154414