Date of Award
Master of Science
Molecular Biology Microbiology and Biochemistry
Type II diabetes is one of the leading cause of morbidity in the U.S. and other parts of the world. Insulin resistance which precedes Type II diabetes is a complex state of the body where the body fails to respond to insulin. Its complexity lies in its multifactorial origin that is to say various environmental and polygenic components come into play. Here we try to dissect one of these components - `Alox8' in transgenic mice and try to see if it affects blood glucose homeostasis. Comparison of glucose tolerance and insulin sensitivity among sixteen mice comprising of six wild type, five heterozygous and five knockout mice with respect to Alox8 gene showed that wild type mice had relatively more glucose tolerance than knockout mice and this corresponded with relatively more insulin sensitiveness of wild type mice with respect to the knock out. However, these findings were not significant statistically at p=0.05. In search of any relevant biological significance, periodic acid schiff staining of the liver sections from these mice in three independent repeated experiments revealed that the knockout phenotype led to accumulation of glycogen deposits as compared to the wild type mice, an indication of insulin resistance. Taken together, our data suggests that these findings when extrapolated to human which carries ALOX15B instead of mice orthologue Alox8, could lead to a benefit of administration of lower doses of insulin in the wild type phenotype as compared to its polymorphic alleles carrying individuals.
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