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Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice

  • Authors:
    • Qiong Huang
    • Qi Gong
    • Ting Wen
    • Shanshan Feng
    • Jixiong Xu
    • Jianying Liu
    • Xiudan Han
    • Qun Liu
    • Juan Hu
    • Lingyan Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Center Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Cardiovascular Medicine, Xiangya Hospital Central South University, Changsha, Hunan 410008, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 23-32
    |
    Published online on: November 21, 2019
       https://doi.org/10.3892/ijmm.2019.4409
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Abstract

Insulin secretion from pancreatic β‑cells regulates glucose metabolism and is related to various diseases including diabetes. The late endosomal/lysosomal adaptor MAPK and mTOR activator 1 (LAMTOR1) is one of the subunits of the ‘Ragulator’ complex and plays an important role in energy metabolism including glucose metabolism. The present study was designed to explore the role of LAMTOR1 in murine pancreatic β‑cell function. A murine model with β cell‑specific deficiency (βLamtor1‑KO) was generated to assess β‑cell function (insulin sensitivity paired with β‑cell responses) by hyperglycemic clamp in vivo. Islet perfusion and mitochondrial functional analyses were performed to investigate the individual steps in the insulin secretion pathway. Results showed that glucose tolerance in vivo as well as glucose‑stimulated insulin secretion in the hyperglycemic clamp and islet perfusion were higher in βLamtor1‑KO mice compared to the control models. Although mitochondrial dysfunction was present, the deletion of Lamtor1 increased glutamate content in the mouse insulin granules as well as acetyl‑CoA carboxylase 1 (ACC1) activity thus enhancing insulin secretion. Together, our data indicate that LAMTOR1 is important for maintaining mitochondrial function in mouse pancreatic β‑cells, however deletion of Lamtor1 increases the amplification pathway induced by glutamate and ACC1, ultimately leading to increased insulin secretion. These findings suggest that knockout of Lamtor1 is a potential technique for improving pancreatic β‑cell function and treating diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Huang Q, Gong Q, Wen T, Feng S, Xu J, Liu J, Han X, Liu Q, Hu J, Zhu L, Zhu L, et al: Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice. Int J Mol Med 45: 23-32, 2020.
APA
Huang, Q., Gong, Q., Wen, T., Feng, S., Xu, J., Liu, J. ... Zhu, L. (2020). Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice. International Journal of Molecular Medicine, 45, 23-32. https://doi.org/10.3892/ijmm.2019.4409
MLA
Huang, Q., Gong, Q., Wen, T., Feng, S., Xu, J., Liu, J., Han, X., Liu, Q., Hu, J., Zhu, L."Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice". International Journal of Molecular Medicine 45.1 (2020): 23-32.
Chicago
Huang, Q., Gong, Q., Wen, T., Feng, S., Xu, J., Liu, J., Han, X., Liu, Q., Hu, J., Zhu, L."Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice". International Journal of Molecular Medicine 45, no. 1 (2020): 23-32. https://doi.org/10.3892/ijmm.2019.4409
Copy and paste a formatted citation
x
Spandidos Publications style
Huang Q, Gong Q, Wen T, Feng S, Xu J, Liu J, Han X, Liu Q, Hu J, Zhu L, Zhu L, et al: Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice. Int J Mol Med 45: 23-32, 2020.
APA
Huang, Q., Gong, Q., Wen, T., Feng, S., Xu, J., Liu, J. ... Zhu, L. (2020). Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice. International Journal of Molecular Medicine, 45, 23-32. https://doi.org/10.3892/ijmm.2019.4409
MLA
Huang, Q., Gong, Q., Wen, T., Feng, S., Xu, J., Liu, J., Han, X., Liu, Q., Hu, J., Zhu, L."Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice". International Journal of Molecular Medicine 45.1 (2020): 23-32.
Chicago
Huang, Q., Gong, Q., Wen, T., Feng, S., Xu, J., Liu, J., Han, X., Liu, Q., Hu, J., Zhu, L."Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice". International Journal of Molecular Medicine 45, no. 1 (2020): 23-32. https://doi.org/10.3892/ijmm.2019.4409
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