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  • Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis

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Pathophysiology/Complications
Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis
  1. Peng Qu1,
  2. Yachun Wang1,
  3. Lei Liu2,
  4. Mengmeng Qi1,
  5. Yimeng Sun1,
  6. Siyang Zheng3,
  7. Zichen Xu1,
  8. Changhong Liu4,
  9. Xiaoyan Bai1,
  10. Qinggao Zhang1,5,
  11. Limin Yang1,5
  1. 1School of Medicine, Dalian University, Dalian, China
  2. 2School of Medicine, Jiamusi University, Jiamusi, China
  3. 3Life Science Institute, Dalian Minzu University, Dalian, China
  4. 4Jiamusi College, Heilongjiang University of Chinese Medicine, Harbin, China
  5. 5Chronic Disease Research Center, Dalian Key Laboratory, Dalian, China
  1. Correspondence to Professor Limin Yang; yanglimin{at}dlu.edu.cn; Professor Qinggao Zhang; zhangqinggao{at}dlu.edu.cn

Abstract

Introduction The habenular nucleus (Hb), a famous relay station in the midbrain, is vital for controlling many physiological functions of vertebrates. The role of Hb in the pathogenesis of depression has been thoroughly studied, but whether it functions in the pathogenesis of diabetes remains unknown. In this study, we found that Hb lesions could improve glucose metabolism in type 2 diabetes mellitus (T2DM) by inhibiting the peripheral sympathetic nervous system and hepatic glucose production.

Research design and methods T2DM rats were induced by a high-carbohydrate and fat diet combined with streptozotocin. Electrical lesion method was applied to suppress the function of Hb. Serum and tissue samples of rats in the control group, T2DM group, sham group, and Hb lesion group were detected by ELISA, western blotting, and biochemical methods.

Results Compared with the sham group, the expression levels of AMPK phosphorylation and insulin receptor (IR) were significantly increased, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxylated kinase were reduced in the liver of the Hb lesion group. In the glucose tolerance test and pyruvate tolerance test, the lesion group showed stronger glucose tolerance and lower hepatic gluconeogenesis than the sham. These results suggest that Hb lesions not only effectively increase insulin sensitivity and improve insulin resistance but also inhibit gluconeogenesis in T2DM rats. Moreover, Hb lesions increase the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, glucocorticoid receptor, and IR in the hippocampus. In this study, we also found that Hb lesions increase the content of acetylcholine in the adrenal glands and reduce the content of epinephrine in both the adrenal glands and the liver, which may be the main reason for the Hb lesions to regulate glucose metabolism in the liver.

Conclusion Hb is an important neuroanatomical target for the regulation of glucose metabolism in the central nervous system of diabetic rats.

  • type 2 diabetes
  • insulin resistance
  • gluconeogenesis
  • central nervous system
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2020-001250

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    Footnotes

    • PQ, YW, LL and MQ contributed equally.

    • Contributors LY, QZ, and LL designed and drafted the manuscript. PQ, YW, and MQ performed the experiments and analyzed the data. YW contributed to the writing of the manuscript. YS, SZ, ZX, and CL performed western blot experiments. XB performed western blot experiments of Akt/P-Akt. All authors read and approved the final manuscript. LY will take responsibility for the contents of the article.

    • Funding This work was supported by the National Natural Science Foundation of China (grant numbers 31571087 and 31200839) and the Educational Department of Liaoning Province (grant number L2019602).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval All rats were cared for and used following the National Institutes of Health guidelines for the care and use of experimental animals, and all procedures were approved by the Animal Care and Use Committee of the Dalian University.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request. The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. LY will take all correspondence of this paper.