Mitochondrial Dysfunction in Type 2 Diabetic Skeletal Muscle Cells

Abstract

Type 2 diabetes (T2D) is an epidemic disease characterized by high blood glucose levels and insulin resistance and is usually associated with obesity. Inadequate glucose utilization by the cell leads to an increase in high fat utilization to make cellular energy, which can lead to mitochondrial dysfunction. Typically, autophagy maintains homeostasis by removing damaged portions of the mitochondria and recycling the functional components to form new efficient mitochondria. The main focus of this project is to analyze if there is an impairment of the autophagy process in T2D that leads to an accumulation of dysfunctional mitochondria. We also evaluated mitochondrial dynamics to determine if the rate of mitochondrial fission exceeds that of fusion, as this may also explain the accumulation. Using an in vitro model of T2D, fluorescent microscopy and biochemical analysis of cells treated with high fats were evaluated to look at mitochondrial dynamics and number. Microscopic analysis showed a decrease in mitochondrial number and a decrease in mitochondrial membrane potential in T2D cells versus control. Furthermore, results revealed that in a diabetic environment there was an increase in mitochondrial fragmentation as seen with an increase in DRP‐1 expression. Lastly, results showed that Beclin‐1 increases under diabetic conditions signifying that autophagy is still being activated. In conclusion, our results demonstrate that there is an increase in mitochondrial fission and activation of autophagy in T2D. More work is needed to determine if fission occurs at a rate faster than the normal autophagy response can handle to explain the consequences of T2D.Support or Funding InformationCalifornia State University, Los Angeles Louis Stokes Alliance for Minority Participation (CSULA‐ LSAMP)andCalifornia State University, Los Angeles Minority Opportunities in Research Programs‐ Minority Biomedical Research Support Program‐Research Initiative for Scientific Enhancement (CSULA MORE‐ RISE Undergraduate)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.