MIR-16 KNOCKOUT REVEALS IMPAIRED INSULIN SENSITIVITY: A PILOT STUDY
Seongkyun Lim, Megan E. Rosa-Caldwell, Wesley S. Haynie, David E. Lee, Tyrone A. Washington, Nicholas P. Greene, FACSM; University of Arkansas, Fayetteville, AR
Type 2 diabetes mellitus (T2DM) has become the most common metabolic disease in western society, leading to serious health problems and financial burdens. Numerous investigations have approached different therapeutics to target T2DM, but the underlying molecular mechanisms are still not completely understood. Our laboratory and others have recently demonstrated consistent downregulation of the microRNA-16 (miR-16) in skeletal muscle across human, rodent and tissue culture models of T2DM. PURPOSE: To investigate how deletion of miR-16 gene affects glucose handling and insulin sensitivity during insulin resistance. METHODS:7 wildtype (WT) and 9 skeletal muscle specific miR-16 knockout (KO) male mice were used for this study. At 9 wks of age, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. At 10 wks of age, half of the mice were given high-fat diet (HFD; 45% calories from fat) to induce insulin resistance, while the remainder were fed with normal chow (NC) as control. At 13 wks of age, GTT and ITT were repeated to examine the effect of HFD in miR-16 KO mice. RESULTS: Body weight was increased by 22.7% in WT mice with HFD and 16.7% in miR-16 KO mice with HFD compared to WT mice with NC.GTT area under curve (AUC) was increased by 30% in miR-16 KO mice with HFD compared to WT mice with NC. ITT data revealed a blunted response to insulin in miR-16 KO mice group with NC and HFD compared to WT mice with NC and HFD. CONCLUSION: Previous data from our group and others that downregulated miR-16 in skeletal muscle across human and animal models of T2DM may be in part due to impaired response to insulin in miR-16 KO condition. Further research is warranted to elucidate molecular mechanisms of miR-16 and its potential role in insulin resistance.
ACKNOWLEDGEMENTS: This study was funded by the Arkansas Bioscience Institute and American College of Sports Medicine Research Endowment Grant.
Lim, S; Rosa-Caldwell, ME; Haynie, WS; Lee, DE; Washington, TA; and Greene, FACSM, NP
"MIR-16 KNOCKOUT REVEALS IMPAIRED INSULIN SENSITIVITY: A PILOT STUDY,"
International Journal of Exercise Science: Conference Proceedings: Vol. 11:
7, Article 52.
Available at: https://digitalcommons.wku.edu/ijesab/vol11/iss7/52