Abstract
The size of skeletal muscle mass plays a significant role in glucose uptake in healthy and diabetic human subjects. Previously, we have generated myostatin-deficient (MSTN−/−) transgenic pigs via animal cloning technology. MSTN−/− pigs had dramatic phenotype with individual muscle mass increase by 100% over their wild-type controls, which provides a unique large animal model to investigate how enhanced skeletal muscles are beneficial to glucose update in diabetes. We employed intravenous administration of stretozotocin (STZ) to male MSTN−/− and wild-type pigs (100 mg/kg body weight). One month later, blood glucose and insulin concentrations and pancreas histology were examined, STZ-induced diabetes occurred in both MSTN transgenic and wild-type pigs. Histology of pancreas, analysis of pAKT and Glut4 transporter proteins by Western blotting, and real-time qPCR for MSTN gene expression were used in the study. The STZ-treated pigs had increased levels of fasting plasma glucose and insulin levels in comparison with animals receiving sodium citrate buffer, their pancreas also had reduced beta cells and slight increases in lymphocyte. There are significant lower concentrations of fasting plasma glucose and insulin in MSTN−/− pigs than that of wild-type pigs after STZ administration. Detections of pAKT and Glut4 transporter proteins by Western blotting in muscle tissue indicates significant elevations of both proteins in MSTN−/− pigs compared with the wild-type pigs. The results from this pig model suggest that enhanced skeletal muscle by manipulation of myostatin function can improve glucose uptake even in the status of diabetes.
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taken from all experimental pigs, were used for the Western blotting analysis. The blots (a) from Western blotting are representative of 12 animals. The relative density values of pAKT and GLUT4 protein levels, calculated by using reference protein GAPDH, are used for producing bar graph (b, c). The levels of P-AKT and GLUT4 in MSTN−/− Meishan pigs were 25% and 40% higher than those of MSTN+/+ Meishan pigs, respectively (P < 0.01). The pAKT and GLUT4 protein levels of MSTN−/− Meishan pigs were 75% and 82% higher than that of MSTN +/+ Meishan pigs (P < 0.01), respectively, in the STZ-administrated pig groups. The percentage of decrease was calculated on the basis of sodium citrate buffer-treated (normal control) group
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Acknowledgements
This work was financially supported by the Key Basic Research Project (2015CB943100), National Transgenic Project of China (2014ZX08006-003, 2016ZX08006-001), the Agricultural Science and Technology Innovation Program of China (ASTIP-IAS05), and an USDA Hatch Project (HAW00244-R) to the College of Tropical Agriculture and Human Resources of the University of Hawaii at Manoa, and The research- funding program from Hunan Agricultural University.
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This research project was conceptualized by Jinzeng Yang and Wentao Cui. Methodology and research work were done by Baio Li and laboratory technicians of CAAS. The manuscript was written by Biao Li and Jinzeng Yang.
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Li, B., Cui, W. & Yang, J. Enhanced skeletal muscle growth in myostatin-deficient transgenic pigs had improved glucose uptake in stretozotocin-induced diabetes. Transgenic Res 29, 253–261 (2020). https://doi.org/10.1007/s11248-020-00194-y
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DOI: https://doi.org/10.1007/s11248-020-00194-y