Insulin sensitivity has been positively correlated with a healthy and extended lifespan, while insulin resistance, decreased insulin sensitivity, has been linked to aging and is the main indicative of type 2 diabetes. Growth Hormone Receptor/ Binding Protein Knockout mice (GHRKO), although obese, are characterized by high insulin sensitivity and a prolonged lifespan. Due to the absence of growth hormone receptors (GHR), growth hormone (GH) is unable to activate its downstream pathway. Interestingly, the secretory activity of visceral fat in GHRKO mice is altered stimulating insulin sensitivity. In this study, we transplanted normal (N) mice with GHRKO visceral fat pads to determine the role of visceral fat developed with the absence of GH signaling on the insulin-signaling pathway in animals with physiologically normal GH action. We found that the visceral fat transplant (VFT) helped the normal mice gain the beneficial effects of fat developed in the absence of GH and caused improvement of their whole body insulin sensitivity when comparing with sham-operated mice and with mice that received visceral fat from N animals. In presented study, RT-PCR was used to determine the levels of hepatic mRNA expression between three experimental groups including Normal-sham mice (N-S), normal mice transplanted with visceral fat from normal animals (N-N), and normal mice receiving visceral fat from GHRKO mice (N-KO). Additionally, Western Blot and ELISA were used to determine the level of total and phosphorylated proteins. By studying the effect of visceral fat transplant from GHRKO or N mice on the whole body insulin signaling in N male mice, and testing different genes expression and proteins quantification, we can shed light on the mechanism by which white adipose tissue (WAT) regulates whole body insulin sensitivity and longevity as well as understanding the role of WATs in development of diabetes and the process behind insulin resistance.
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Masternak, Michal M.
Bachelor of Science (B.S.)
College of Medicine
Dissertations, Academic -- Medicine; Medicine -- Dissertations, Academic
Length of Campus-only Access
Honors in the Major Thesis
Bennis, Mohammed, "Effects of GHRKO Visceral Fat Transplant on Insulin Signaling" (2015). HIM 1990-2015. 1785.