Correction: Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia

摘要: Recurrent hypoglycemia can occur as a major complication of insulin replacement therapy, limiting the long-term health benefits intense glycemic control in type 1 and advanced 2 diabetic patients. It impairs normal counter-regulatory hormonal behavioral responses to glucose deprivation, phenomenon known associated autonomic failure (HAAF). The molecular mechanisms leading defective counter-regulation are not completely understood. We hypothesized that both neuronal (excessive cholinergic signaling between splanchnic nerve fibers adrenal medulla) humoral factors contribute impaired epinephrine production release HAAF. To gain further insight into mechanism(s) mediating blunted following recurrent hypoglycemia, we utilized global gene expression profiling approach. characterized transcriptomes during (defective model) acute (normal group) medulla Sprague-Dawley rats. Based on comparison analysis differentially expressed genes, set unique genes activated only at specific time points after were revealed. A complementary bioinformatics functional category, pathway, integrated network indicated activation unfolded protein response. Furthermore, least three additional pathways/interaction networks altered identified, which may secretion HAAF: greatly increased neuropeptide (proenkephalin, Y, galanin); ion homeostasis (Na+, K+, Ca2+) downregulation involved Ca2+-dependent exocytosis secretory vesicles. Given pleiotropic effects response different organs, maintaining homeostasis, these findings uncover broader general arise afford clinicians an opportunity modulate magnitude HAAF syndrome.