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SNieuwoudt Dissertation - Final.pdf (3.18 MB)

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Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models

Nieuwoudt, Stephan
http://orcid.org/0000-0003-4857-2211
http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227

Abstract Details

2018, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
The beneficial effects of exercise for patients with type 2 diabetes (T2D) has been well established through critical advances in metabolic research. Two of the key benefits of exercise in T2D include improved insulin sensitivity and pancreatic ß-cell function, as defects in these systems primarily drive glucose intolerance in this patient population. The underlying mechanisms behind these benefits of exercise in T2D are still unknown, despite decades of intense investigation. First, this dissertation provides additional evidence that exercise, especially at a high intensity, can improve ß-cell function in adults with T2D. Myokine secretion from skeletal muscle may provide the mechanistic link between exercising skeletal muscle and the insulin secreting pancreatic ß-cell. Determining this direct cross-talk effect required the development of an “exercise in a petri dish” system, enabling the isolation of the systemic effects of exercise and muscle contraction alone. Details are provided for the development of a successful in vitro contraction system using C2C12 myotubes, along with design information for the construction of a platinum wire electrode system. First, the model had to be validated against a complicated exercise-mediated phenomenon. The accumulation of excess saturated lipid in plasma has been implicated in both the development of insulin resistance and T2D, with prior exercise protecting against lipid-induced insulin resistance. In vitro contraction of muscle cells via electrical stimulation is shown here to effectively protect against lipid-induced insulin resistance, evident at the levels of glucose uptake and proximal insulin signaling. With a validated model in hand, the crosstalk of contracting muscle and ß-cells (MIN6) was evaluated. Secretory products from contracted C2C12 myotubes were able to enhance MIN6 glucose stimulated insulin secretion, providing experimental support for exercise-mediated crosstalk. These data establish the central role of muscle contraction in driving improved insulin sensitivity and ß-cell function in T2D.
John Kirwan, PhD, FACSM (Advisor)
George Dubyak, PhD (Committee Chair)
Michelle Puchowicz, PhD (Committee Member)
Julian Stelzer, PhD (Committee Member)
Xin Yu, ScD (Committee Member)
185 p.
Biomedical Research; Biophysics; Molecular Biology; Physiology
Type 2 Diabetes; Exercise; Skeletal Muscle; In Vitro; Myokines; Insulin Resistance; Beta Cell Function

Recommended Citations

Citations

  • Nieuwoudt, S. (2018). Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227

    APA Style (7th edition)

  • Nieuwoudt, Stephan. Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models. 2018. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227.

    MLA Style (8th edition)

  • Nieuwoudt, Stephan. "Insights into the Functional Roles of Exercise in Type 2 Diabetes Using in vitro Models." Doctoral dissertation, Case Western Reserve University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1512565582988227

    Chicago Manual of Style (17th edition)

case1512565582988227
270
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.