Serine/threonine protein phosphatase 1 (PP1) is an abundant serine/threonine phosphatase which regulates a variety of cellular processes through protein dephosphorylation. PP1 contains 2 subunits, the catalytic subunit (PP1c) and the regulatory subunit (PP1r). The catalytic subunit is non-specific and requires interaction with regulatory subunits for its specificity. We hypothesized that upon high glucose high insulin treatments, PP1c and/or PPP1R12 abundance is abnormal in primary human skeletal muscle cells derived from lean healthy participants. Our study aims to determine the abundance of PP1c and/or PPP1R12 in primary human skeletal muscle cells derived from lean healthy participants among 4 different treatments: low glucose (5.6mM/100mg/dL) no insulin for 2 days without acute 15-min insulin treatment (LGNI BAS), low glucose (5.6mM/100mg/dL) no insulin for 2 days with acute 15-min insulin (100nM) treatment (LGNI INS), high glucose (25mM/450mg/dL) high insulin (100nM) for 2 days without acute 15-min insulin stimulation (HGHI BAS) and high glucose (25mM/450mg/dL) high insulin (100nM) for 2 days with acute 15-min insulin (100nM) stimulation (HGHI INS). We optioned to use high glucose high insulin treatment because it mimics the hyperglycemic hyperinsulinemia condition to which skeletal muscle cells are exposed in insulin resistant individuals. Towards this end, primary human skeletal muscle cells were cultured from muscle biopsies of 6 lean healthy participants. Those cells were treated with four different conditions described above. The results indicated that chronic high glucose high insulin treatment on primary skeletal muscle cells derived from lean healthy insulin sensitive participants led to increased protein abundance of PP1c. This increase might increase the activity of the PP1c/PPP1R12 complex and may be a result of compensating the effect of serine/threonine kinases that may also be over-activated upon chronic high glucose high insulin treatment. The results provide the 1st evidence that a catalytic subunit of serine/threonine phosphatase protein phosphatase 1, PP1c, exhibits abnormal protein abundance in primary skeletal muscle cells in hyperglycemic hyperinsulinemic conditions, which may play a role in the development of insulin resistance.
|Commitee:||Berlie, Helen, Chen, Fei|
|School:||Wayne State University|
|School Location:||United States -- Michigan|
|Source:||MAI 57/04M(E), Masters Abstracts International|
|Subjects:||Pharmacology, Pharmaceutical sciences|
|Keywords:||Human skeletal muscle, Hyperglycemic hyperinsulinemic, Insulin resistance, PP1c, Primary skeletal muscle cells, Type 2 diabetes|
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