Effects of High-Insulin Exposure on Mitochondrial Content in Skeletal Muscle Myotubes from Lean & Severely Obese Individuals: A Time Course Analysis

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Kristen D Turner (Creator)
Institution
East Carolina University (ECU )
Web Site: http://www.ecu.edu/lib/

Abstract: Skeletal muscle is the site at which highly regulated energetic processes take place as a means of maintaining both tissue-specific and whole-body metabolism. With the development of severe obesity (BMI [greater-than] or equal to 40 kg/m2), skeletal muscle often loses its ability to properly respond to insulin, which aside from regulating glucose, has also been suggested to regulate factors specific to mitochondrial biogenesis. In this study, we classified human skeletal muscle cells (HSkMCs) derived from lean and severely obese individuals. We found them to be strikingly similar with respect to their proliferation and differentiation behavior. Also, to test the hypothesis that insulin would increase proteins associated with mitochondrial biogenesis, mature myotubes were treated with 100nM insulin at time points ranging from 1-24 hours. To validate our model, we incorporated a number of methodologies, including measures of AKT phosphorylation, which we found to be 51% lower in the obese group at the first hour (p = 0.05). However, 100nM insulin produced no changes in protein content of PGC-1[alpha], nor OXPHOS proteins, Complex V or Complex III. This high-insulin treatment did result in increases in Complex IV at 3 hours (p = 0.02), as well as the slow isoform of MYHC (at multiple time points) in both groups. We also observed trends for decreases in intracellular ATP at 24 hours of high-insulin treatment in both lean and severely obese groups. Collectively, these data demonstrate that insulin produces no consistent increases in mitochondrial biogenesis as defined by PGC-1[alpha] and OXPHOS proteins in myotubes from lean and severely obese individuals. We further conclude that the responses to sustained, high-insulin exposure in these groups are alike as it relates to increases in protein synthesis (i.e., MYHC (slow)) at the rather costly expense of ATP.

Additional Information

Publication
Thesis
Language: English
Date: 2016
Keywords
ATP, severe obesity, AKT, myosin heavy chain, lactate, glucose, human, skeletal muscle, cell culture, PGC-1a
Subjects
Satellite cells; Proteins--Synthesis; Obesity; Mitochondria--Formation; Muscle cells; Insulin

Email this document to

This item references:

TitleLocation & LinkType of Relationship
Effects of High-Insulin Exposure on Mitochondrial Content in Skeletal Muscle Myotubes from Lean & Severely Obese Individuals: A Time Course Analysishttp://hdl.handle.net/10342/5918The described resource references, cites, or otherwise points to the related resource.