Presenter(s): Shawn Melendy
Faculty Mentor(s): Carrie McCurdy & Byron Hetrick
Poster 7
Session: Sciences
Type 2 Diabetes is an increasingly prevalent disease worldwide that is partially caused by a progressive loss of insulin response in adipose tissue and skeletal muscle, two essential insulin target tissues. The class 1A phosphatidylinositol-3-kinase (PI3K) plays a central role in the insulin signal transduction cascade, as it controls the first point of signal propagation. It has been previously shown that the PI3K regulatory subunits (p85α/p55α/p50α) are upregulated in adipose tissue from high-fat diet (HFD) fed obese mice, concurrent with insulin resistance. Obese, insulin resistant adipose tissue is also characterized by chronic, low grade inflammation. This elevated inflammation attenuates signaling through the PI3K/Akt signaling pathway contributing to insulin resistance. The objective of this study is to determine how adipocyte specific overexpression of p85α affects insulin signaling in adipose tissue, independent of obesity. We have generated a lean mouse model designed to overexpress p85α in an adipocyte- specific manner, and measured insulin response in white adipose tissue (WAT) via Simple Western probing for phosphorylated Akt (pAkt). No significant difference in pAkt has been observed compared to wild-type, though the data trends towards increased signaling in p85α overexpressing (OX) mice. Additionally, p85α OX mice show no significant change in insulin sensitivity, as observed by an oral glucose tolerance test (OGTT). These results prompt the need for further validation of the overexpression of p85α in the transgenic mice. Future work will include measuring WAT p85α abundance via Simple Western, p85α transcript abundance via RT- qPCR, and detecting the presence of the p85α-inserted transgene with PCR.