Sympathetic Innervation of Human Alpha Cells
| Autor: | Clayton E. Mathews, Ivan C. Gerling, Katelyn N. Carty, Kamal Nasif, Elizabeth A. Butterworth, Mark A. Atkinson, Lith H. Nasif, Martha Campbell-Thompson |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty geography Type 1 diabetes geography.geographical_feature_category Vascular smooth muscle endocrine system diseases Tyrosine hydroxylase Chemistry Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Glucagon secretion Alpha (ethology) Islet medicine.disease 03 medical and health sciences 030104 developmental biology Endocrinology Internal medicine Internal Medicine medicine Neural cell adhesion molecule |
| Zdroj: | Diabetes. 67 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db18-1799-p |
| Popis: | Autonomic input is critical for the regulation of glucagon secretion to maintain blood glucose levels. Glucagon secretion is abnormal in patients with type 1 diabetes (T1D) and we hypothesize this results from dysfunctional sympathetic innervation of alpha-cells and may be present in at-risk autoantibody positive (AAb+) individuals. To characterize alpha-cell sympathetic innervation, pancreas tail samples were used from age-matched organ donors in three groups: controls (n=6), AAb+ (4), and T1D (4). Fresh frozen 40μm sections or 1-2 cm optically cleared samples were stained with markers for neuroendocrine cells (GCG, INS), total (NCAM)/ sympathetic nerves (tyrosine hydroxylase (TH)), and vascular smooth muscle cells (SMA) followed by confocal and Lightsheet imaging. To determine whether sympathetic fibers were decreased in AAb+ and/or T1D donors, TH+ fiber numbers were counted within islets and the percentage (%) of TH+ fibers/NCAM+ fibers determined. The TH+ fibers/islet were not significantly different between controls (1.5 ± 0.36, n=6), AAb+ (1.2 ± 0.27 (4)), and T1D (1.8 ± 0.57 (4)) donors (p = 0.07, ANOVA) with similar results for TH+ %. TH+ fibers were observed at alpha-cells in all donors. TH+ nerve densities were also similar between islets and exocrine regions between groups. Microarray analysis of single islet transcriptomes obtained using laser microdissection (n=120 islets, 13 control, 12 T1D) showed decreased expression of VMAT2 in insulin+ islets from T1D donors compared to control islets (p=0.047) while insulin- islets in T1D donors had significantly reduced VMAT2 levels compared to control islets (p Disclosure E.A. Butterworth: None. L.H. Nasif: None. K. Nasif: None. K.N. Carty: None. C.E. Mathews: None. M.A. Atkinson: Other Relationship; Self; Patent Issued. I.C. Gerling: None. M. Campbell-Thompson: None. |
| Databáze: | OpenAIRE |
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