Genetic drivers of insulin homeostasis.

Document Type

Article

Publication Date

Summer 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory

Abstract

Development of severe insulin resistance and the failure of pancreatic beta cells to secrete more insulin in compensation for attenuated insulin insensitivity are hallmarks of Type 2 Diabetes. As Type 2 Diabetes becomes more and more prevalent around the world, identifying specific genetic mechanisms that underlie the regulatory processes of insulin homeostasis becomes extremely critical. In this study, we used computational tools to analyze a dataset of 378 Diversity Outbred mice retained on a high fat diet. Through Quantitative Trait Locus Mapping, we have identified a viable explanation for the frequently cited relationship between Hnfl b and Type 2 Diabetes, in which a single nucleotide mutation within the protein-coding region of Hnfl b is able to affect peripheral insulin sensitivity 10. Our studies also propose novel associations between single nucleotide polymorphisms in Cell and Synrg with variation in insulin homeostasis. Findings in this study can be applied to a wet lab environment in order to test the relationship of SNPs rs222172612, rs230667983 , and rs28243674 in genes Ccll , Hnfl b, and Synrg respectively with insulin homeostasis. This study suggests that Ccll , Hnfl b, and Synrg may be potential therapeutic targets for patients suffering from Type 2 Diabetes. A hallmark of Type 2 Diabetes is the development of severe insulin resistance accompanied by the failure of pancreatic beta cells to secrete more insulin in compensation for attenuated insulin insensitivity. As Type 2 Diabetes becomes more and more prevalent around the world, identifying specific genetic mechanisms that underlie the regulatory processes of insulin homeostasis becomes extremely critical. In this study, we used computational tools to analyze a dataset of378 Diversity Outbred mice retained on a high fat diet. Through Quantitative Trait Locus Mapping, we have identified a viable explanation for the frequently cited relationship between Hnfl b and Type 2 Diabetes, in which a single nucleotide mutation within the protein-coding region of Hnfl b is able to affect peripheral insulin sensitivity 10. Our studies also propose novel associations between single nucleotide polymorphisms in Cell and Synrg with variation in insulin homeostasis. Findings in thi s study can be applied to a wet lab environment in order to test the relationship of SNPs rs222 172612, rs230667983 , and rs28243674 in genes Cell, Hnfl b, and Synrg respectively with insulin homeostasis. This study suggests that Ccll , Hnfl b, and Synrg may be potential therapeutic targets for patients suffering from Type 2 Diabetes.

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