Spinal cord injury causes insulin resistance associated with PI3K signaling pathway in hypothalamus.

Abstract

Spinal cord injury (SCI) is an independent risk factor for type 2 diabetes, and may induce insulin resistance that leads to this disease. Studies have shown that greater phosphoinositide 3-kinase (PI3K) activation in the hypothalamus leads to activation of the anti-inflammatory pathway, and the anti-inflammatory reflex may protect against insulin resistance and type 2 diabetes. However, the importance of this phenomenon in type 2 diabetes pathogenesis after SCI remains elusive. In the present study, the expression of c-Fos in the hypothalamus of rats with SCI was elevated, and the hypothalamus injury was observer following SCI. Then we showed that SCI could induce increased levels of blood glucose and glucose tolerance in rats. Also, we found that SCI could damage the liver, adipocyte and pancreas, and led to lipid position in liver. Western blots were used to detect the level of PI3K and p-Akt in the hypothalamus, and the results showed a significant downregulation of PI3K and p-Akt after SCI. Furthermore, to verify the activity of the PI3K signaling pathway, immunofluorescence was used to examine the expression of neurons positive for p-S6 (a marker of PI3K activation) after SCI. The results showed that the expression of p-S6-positive neurons decreased after SCI. In addition, the effect of SCI on peripheral inflammation was also investigated. Following SCI, the serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 increased. Collectively, our results suggest abnormality in glucose metabolism after SCI, and demonstrate that SCI may impair activation of the PI3K signaling pathway in the hypothalamus. The reduced activity of the PI3K signaling pathway in the hypothalamus may lead to peripheral inflammation, which might be the mechanism underlying the development of insulin resistance and type 2 diabetes following SCI.

• Authors: Rui-Dong Cheng, Wen Ren, Peng Sun, Liang Tian, Li Zhang, Jie Zhang, Jue-Bao Li, Xiang-Ming Ye
• Journal: Neurochemistry international (Neurochem Int) Vol. 140 Pg. 104839 (11 2020) ISSN: 1872-9754 [Electronic] England
• PMID: 32853751 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier Ltd.

Topics

• Animals
• Hypothalamus (metabolism, pathology)
• Insulin Resistance (physiology)
• Male
• Phosphatidylinositol 3-Kinases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Spinal Cord Injuries (metabolism, pathology)
• Thoracic Vertebrae (injuries)