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Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery

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Abstract

The Roux-en-Y gastric bypass (RYGB) is a one-of-a-kind treatment among contemporary bariatric surgical procedures, and its therapeutic effects for type 2 diabetes mellitus (T2DM) are satisfactory. The present study performed isobaric tags for relative and absolute quantification (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis identifying different proteomics between T2DM rats with or without Roux-en-Y gastric bypass (RYGB) surgery, and GTP binding elongation factor GUF1 (Guf1) was first found to be significantly upregulated in rats from the T2DM plus RYGB group. In the cellular lipotoxicity model induced by palmitic acid stimulation of rat pancreatic beta cell line, INS-1, palmitic acid treatment inhibited cell viability, suppressed GSIS, promoted lipid droplet formation, promoted cell apoptosis, and induced mitochondrial membrane potential loss. The effects of palmitic acid on INS-1 cells mentioned above could be partially eliminated by Guf1 overexpression but aggravated by Guf1 knockdown. Last, under palmitic acid treatment, Guf1 overexpression promotes the PI3K/Akt and NF-κB signaling but inhibits the AMPK activation. Guf1 is upregulated in T2DM rats who received RYGB, and Guf1 overexpression improves cell mitochondrial functions, increases cell proliferation, inhibits cell apoptosis, and promotes cell functions in palmitic acid-treated β cells.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (No. YX202106).

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Authors and Affiliations

  1. Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Pengzhou Li, Song Dai, Xiang Gao & Weizheng Li

Authors
  1. Pengzhou Li
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  2. Song Dai
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  3. Xiang Gao
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  4. Weizheng Li
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Contributions

Weizheng Li and Pengzhou Li conceptualized and designed the experiments. Pengzhou Li drafted the article. Weizheng Li revised the article critically for important intellectual content. Pengzhou Li, Song Dai, and Xiang Gao contributed to cell and animal experiments. Song Dai and Xiang Gao contributed to the analysis and manuscript preparation. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Weizheng Li.

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N/A.

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Approval date of registry and the registration no. of the study/trial

N/A.

Animal studies

The animal experiments were approved by the Ethics Committee of Central South University (approval no. 2019–S383).

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The authors declare no competing interests.

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Key points

• Guf1 was upregulated in pancreatic tissues in T2DM rats with RYGB surgery.

• Guf1 improves palmitic acid-induced dysfunctions of rats’ islet β cells.

• Guf1 improves palmitic acid-induced mitochondrial dysfunction and apoptosis.

• Guf1 promotes the PI3K/Akt and NF-κB signaling but inhibits the AMPK activation.

Supplementary Information

Additional file 1: Fig. S1. 

Determination of Mrps16 and Guf1 expression. (A) Mrps16 and Guf1 expression in pancreatic tissues from T2DM and T2DM+RYGB rats. (B) Mrps16 and Guf1 expression in INS-1 cells treated with or without PA. 

Additional file 2: Fig. S2.

Effects of lentivirus of overexpressing Guf1 or knockdown Guf1 on INS-1 cells viability. INS-1 cells were non-transduced or transduced with lentivirus overexpressing Guf1 (lv-Guf1) or lentivirus knockdown Guf1 (sh1-Guf1 or sh2-Guf1) and then examined for cell viability by MTT assay. 

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Li, P., Dai, S., Gao, X. et al. Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery. J Physiol Biochem 79, 569–582 (2023). https://doi.org/10.1007/s13105-023-00952-6

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  • DOI: https://doi.org/10.1007/s13105-023-00952-6

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