Master of Science

thesisThe purpose of this study is to define the impact of dietary magnesium (Mg) upon insulin signaling transduction in skeletal muscle during development of diabetes. Chronic under-consumption of Mg coexists with rising rates of diabetes. To assess the relationship of Mg intake on insulin-stimulated transduction in skeletal muscle, TallyHo (TH) diabetic mice (n=8/group) were fed a specialized diet from 8 to 16 weeks of age consisting of low Mg (L-Mg, 100 mg Mg/kg chow), standard Mg (S-Mg, 500 mg Mg/kg chow), or high Mg (H-Mg, 1000 mg Mg/kg chow). C57BLK6 mice were used as controls (Con) fed diets with standard Mg. Results indicate that compared to Con, L-Mg and S-Mg groups had higher fasting blood glucose levels and worse insulin sensitivity as determined by Insulin Tolerance Test (ITT) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). In contrast, H-Mg mice had a partial recovery of fasting glucose and HOMA-IR. Liver GSK phosphorylation was assessed as a surrogate of glycogen synthesis, and was found to be similar between all TH diabetic groups, and similar to Con. Despite improved HOMA-IR in H-Mg, there were no corresponding changes in skeletal muscle insulin-stimulated signal transduction vs. S-Mg or L-Mg. In fact, the L-Mg group demonstrated an increase in insulin-stimulated Akt phosphorylation from basal levels, whereas the S-Mg and H-Mg groups did not. We conclude that alterations in HOMA-IR in TH mice varying levels of Mg are not associated with increased insulin sensitivity in skeletal iv muscle. This is in agreement with our previous work that also reported no changes in hepatic insulin-mediated signaling transduction