Structure Function Relationship of Myo-Inositol Oxygenase in Model Drosophilids and its Role in Obesity

• Main Author: Smith, Matthew Barrett Toshio
• Language: EN
• Published: California State University, Long Beach 2017
• Subjects: Biology|Genetics
• Online Access: http://pqdtopen.proquest.com/#viewpdf?dispub=10289008

<p> Diabetes mellitus is the 7^th leading cause of death in the United States, with the most prevalent form being type II diabetes (T2D). T2D has a strong genetic component, but environmental factors like poor diet and lack of physical activity are major risk factors. T2D is characterized by the inability of insulin sensitive cell to respond to insulin, which leads to the reduction of glucose uptake. As a result diabetic patients excrete large amounts of glucose in their urine, but they also excrete large amount of <i>myo</i>-inositol (MI). MI is a six-carbon sugar alcohol that is a precursor to the phospholipid component, phosphatidylinositol. MI is also involved with other cellular functions as an insulin mimetic, a carbon/energy source, a phosphate storage molecule, and as an osmolyte. MI levels are regulated by synthesis, transport, recycling, and catabolism. Diabetic tissues have been found to have lower levels of MI. Moreover, the enzyme that catabolizes MI, myo-inositol oxygenase (MIOX), has been shown to be up-regulated in the renal tissue of diabetic patients. This study focuses on MI catabolism. Over the past decade <i>Drosophila melanogaster</i> has emerged as good organism to model diabetes and its associated complications. However, the <i> MIOX</i> gene has not been characterized in drosophilids. In this study the <i>MIOX</i> gene was characterized for seven drosophilid species, and the presence of the MIOX protein was established by demonstrating the ability of each species to utilize MI as the sole energy source. The steady-state levels of MIOX transcript in each of the species was shown to be higher in larvae grown with dietary inositol. Wild-type larvae grown under diabetic conditions (with high levels of sucrose) have decreased steady-state levels of <i>MIOX</i> transcript. Reducing the expression of MIOX results in larvae with a higher body density yet more triacylglycerides. Additionally, when expression of MIOX is knocked-down under diabetic conditions, abnormal lipid droplet storage is observed. These studies may contribute to the understanding of the role of MIOX in diabetic conditions such as obesity.</p><p>