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Sympathetic decentralization after spinal cord injury spares Zucker Diabetic Fatty rats from frank diabetes
Author(s) -
PoormasjediMeibod MaliheSadat
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1013.7
Subject(s) - insulin resistance , medicine , endocrinology , metabolic syndrome , dyslipidemia , type 2 diabetes , diabetes mellitus , spinal cord injury , insulin , spinal cord , psychiatry
Introduction Metabolic syndrome, characterized by the constellation of visceral obesity, atherogenic dyslipidemia, proinflammatory state, hypertension, and insulin resistance, confers a 5‐fold increase in the risk of type 2 diabetes (T2D). Accumulating data from human and animal studies revealed a strong association between sympathetic nervous system (SNS) activation and different components of metabolic syndrome, such as obesity, hypertension, and insulin resistance. However, it is not clear whether sympathoexcitation is a cause or result of metabolic syndrome and the subsequent T2D. Here we used high thoracic spinal cord injury (SCI) as an effective means for SNS decentralization in order to investigate the potential role of the SNS in the pathogenesis of T2D in an animal model of metabolic syndrome. Method/Design Eighteen male Zucker Diabetic Fatty rats (ZDF‐Lepr fa/fa , Metabolic syndrome/T2D animal model) were evenly assigned to two groups: uninjured (Fatty‐Sham), and T3 complete SCI (Fatty‐SCI). Lean Zucker Diabetic Fatty rats (ZDF‐Lepr + , n = 9) acted as controls. T2D development was evaluated using biweekly random blood glucose measurements and oral glucose tolerance test (OGTT) at week 11 post‐injury. Twelve weeks post‐injury, animals were euthanized and blood samples and pancreas tissue were collected for further analyses. Results We found that SCI‐induced SNS decentralization, manifested by a dramatic decline in plasma norepinephrine (P = 0.011), was accompanied by improved glucose tolerance, i.e. decreased glucose area under the curve (AUC, P = 0.001), increased fasting insulin (1.00 ± 0.33 vs. 3.02 ± 1.5 ng/ml, p = 0.011), and augmented insulin response after an OGTT, i.e. increased insulin AUC (P = 0.001) in the Fatty‐SCI group compared to uninjured Fatty‐Sham group. Although Fatty‐Sham and Fatty‐SCI groups exhibited a comparable degree of insulin resistance, Fatty‐SCI had significantly higher β‐cell activity indicated by a significant increase in homeostatic model assessment‐%B (HOMA‐%B) index (P = 0.0064). Pancreatic gene expression analysis revealed that SCI caused a significant reduction in the local expression of inflammatory mediators, i.e. IL‐1β and TNF‐α, which are critical for inhibition of insulin secretion, and induction of β‐cell apoptosis and dysfunction. While SNS decentralization spared the Fatty‐SCI rats from frank diabetes, Fatty‐SCI and Fatty‐Sham rats both exhibited other components of metabolic syndrome, including abdominal obesity and dyslipidemia, as compared to lean rats. Support or Funding Information This work has been supported by Michael Smith Foundation for Health Research, Craig H. Neilsen Foundation, Heart and Stroke Foundation of Canada, and the International Collaboration on Repair Discoveries.