Date of Award


Degree Name

Biological Sciences


College of Science

Type of Degree


Document Type


First Advisor

Eric R. Blough

Second Advisor

Simon Collier

Third Advisor

David S. Mallory


Metabolic syndrome is characterized by insulin resistance and hyperglycemia. The molecular mechanism(s) underlying this alteration in skeletal muscle, liver, kidneys and heart in metabolic syndrome patients are presently unclear. Recent data have demonstrated that the p38and extracellular-signal-regulated kinases (ERK 1/2) - mitogen-activated protein kinase (MAPK) proteins may be involved in the regulation of (Glucose transporter type 4) GLUT4 expression levels. Other data have suggested that miRNA may also play a role. Purpose: The purpose of this study is to compare the tissue content, phosphorylation of protein kinases (AKT), p38, c-JUN Nterminal kinase(JNK), ERK1/2, GLUT4 and transcriptional factor Myocyte enhancer factor-2 (MEF2) in the skeletal muscle, heart, liver and kidney of insulin resistant obese (fa/fa) and lean Zucker rats. Methods: Skeletal muscle, heart, liver and kidney were obtained from obese (n=6) and lean (n=6) Zucker rats. The amount and phosphorylation status of AKT, p38, JNK, ERK 1/2, GLUT4 and MEF2 were evaluated by immunoblotting. Results: Decreased GLUT4 expression levels were observed in the skeletal muscle, liver and heart of obese Zucker rats compared to lean zucker rats and are associated with alterations in the phosphorylation of MAPK family members.Levels of mir-1and 133a were altered in skeletal and cardiac muscles of obese Zucker rats when compared with their lean counterparts. Conclusions: These results suggest that MAPK members regulate GLUT4 expression differently in various insulin resistant tissues compared to lean counterparts and that these changes may play a key role in insulin resistance associated with glucose dysregulation.


Blood sugar - Research


Obesity - Research