The Effect of Inhibiting Fatty Acid Oxidation on Basal Glucose Metabolism

We administered etomoxir (an inhibitor of fatty acid oxidation) for five days at a dose of 50 mg/kg/day to three groups of Psammomys obesus. Group A were normoglycemic and normoinsulinemic, group B were normoglycemic and hyperinsulinemic, and group C were hyperglycemic and hyperinsulinemic. When compared with group A, the hyperglycemic/hyperinsulinemic rats of group C had elevated hepatic glucose production (HPG) and elevated glucose uptake (Rg) in all tissues measured reaching statistical significance in white gastrocnemius, soleus and diaphragm. Five days of etomoxir treatment reduced the plasma glucose levels of group C. Etomoxir treatment reduced HGP and although the change was not significant, it was supported by significant reductions of Rg in several tissues including diaphragm, heart, small intestine, brain and white adipose tissue. Five days of etomoxir treatment also reduced the plasma insulin levels in group B and group C, when compared to the levels before treatment. These results demonstrate that inhibition of fatty acid oxidation significantly reduced hyperglycemia, hyperinsulinemia and Rg in some tissues in group C animals suggesting that elevated levels of fatty acid oxidation and increased glucose turnover may be associated with development of NIDDM in Psammomys obesus.

Key words

Hepatic Glucose Production - Glucose Uptake - Animal Models - Glucose Turnover - Fatty Acid Oxidation