ENHANCED INSULIN SIGNALING FOLLOWING CONTRACTILE ACTIVITY IS BLUNTED IN MYOTUBES FROM SEVERELY OBESE INDIVIDUALS WITH OR WITHOUT TYPE 2 DIABETES

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Seongkyun Lim (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Introduction: Regular exercise has been known to improve insulin sensitivity in obese/ Type 2 Diabetic (T2D) individuals. However , some obese and T2D individuals do not respond well to regular exercise in their metabolic health. Purpose: The purpose of this study was to test the hypothesis that contractile activity in severely obese individuals (40>BMI) with T2D would be more blunted in insulin signaling and contraction-induced cellular activities in response to contractile activity compared to lean and severely obese individuals without T2D. Methods: Lean and healthy subjects (n=11) and severely obese individuals (BMI > 40) with T2D (n=8) and without T2D (n=8) were recruited. Skeletal muscle tissues were taken from each subject through muscle biopsy and differentiated in culture to myotubes to measure insulin sensitivity following contractile activity. The contractile activity was generated by electrical pulse stimulation (EPS) at 11.5 V , 2 ms , and 1Hz for 24 hours. Following EPS , myotubes were incubated with serum starvation media for 3 hours , then treated with insulin for 10 minutes , after which the cell lysate was harvested for western blot analysis to measure protein expression. Results: Phosphorylation of AMPK and ACC were significantly increased both in lean and severely obese group with EPS (P [less than] 0.05) , but not in the T2D group. All participants from each group significantly increased (P [less than] 0.05) their insulin-mediated pAKT and pAS160 and the magnitude of insulin sensitivity was significantly higher (P [less than] 0.05) in the lean group compare to severely obese individuals with or without T2D. Interestingly , the insulin signaling was further increased (P [less than] 0.05) with insulin stimulation following EPS in only the lean group , but this effect was blunted in both severely obese with or without T2D. Conclusion: Our data show that EPS increases insulin signal transduction in myotubes from lean individuals , but this response is absent in myotubes from individuals with severe obesity with or without T2D. The T2D subjects show not only blunted insulin sensitivity but also impaired cellular energy pathways in response to contractile activity , indicating that there is an inherent defect in their cellular response to electrical/contractile activity in severely obese individuals with T2D.

Additional Information

Publication

Thesis

Language: English

Date: 2018

Keywords

Insulin signaling, electrical pulse stimulation, Akt, AMPK, myogenic markers, myogenic markers

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