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Role of COUP‐TFII in Glucose Homeostasis in Dahl Salt Sensitive Rats
Author(s) -
Ashraf Usman Mohammad,
Kumarasamy Sivarajan
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb480
Subject(s) - medicine , endocrinology , biology , homeostasis , glucose homeostasis , gene expression , insulin , gene , insulin resistance , genetics
The Interaction between genetic and environmental factors plays an important role in disease progression. One of the major environmental factor includes diets, which governs significant attention based on the broad spectrum of effect in cardiovascular and associated diseases. Consumptions of diets that are rich in calories and salts can significantly increases the risk for developing life threatening cardiovascular events including hypertension and metabolic syndrome. Through GWAS studies, a locus with significant association for hypertension was found in human chromosome 15 containing the gene Chicken Ovalbumin Upstream Promotor Transcription Factor II ( COUP‐TFII ). To validate this gene, a mutant rat was developed with a 15‐base pair deletion in Dahl Salt Sensitive (SS) rat background. Under high salt diet regimen, the Coup‐TfII mutant rat had an improved cardiac and renal function when compared to SS rats. Being a known transcriptional regulator, Coup‐TfII also plays a role in other physiological events including glucose homeostasis and energy metabolism. In H4IIE rat hepatoma cells, Coup‐TfII expression modulated in response to glucose levels; under high glucose condition Coup‐TfII expression was significantly down‐regulated ( p< 0.05); whereas in low glucose condition Coup‐TfII expression was significantly up‐regulated ( p< 0.05). In addition, Coup‐TfII protein expression is found to negatively correlate with insulin regardless on the amount of glucose present in H4IIE cells ( p< 0.05). Similar to our in‐vitro findings, Coup‐TfII gene expression was significantly up‐regulated in SS rat liver during fasting as compared to re‐fed condition ( p< 0.05). Coup‐TfII mutant rat have also showed a significant decrease in fasting blood glucose levels ( p< 0.05) compared to SS rat along with a significant decrease in their body weight ( p< 0.05) . Furthermore, the Coup‐TfII mutant rat demonstrated a superior glucose response and insulin response as measured by glucose tolerance test (GTT) and Insulin tolerance test (ITT) ( p< 0.05). Further, under fasting condition the mRNA expression analysis in livers of SS and CoupTfII mutant rats revealed that the key enzymes involved in both beta oxidation and gluconeogenesis was significantly down regulated in Coup‐TfII mutant rats compared to SS rats ( p< 0.05). Overall, our preliminary findings suggest that Coup‐TfII is important for glucose homeostasis in SS rats. Further understanding of Coup‐TfII function will help to dissect the relationship between metabolic syndrome and blood pressure regulation in SS rats. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .