Effects of oleanolic acid on small intestine morphology and enzymes of glutamine metabolism in diabetic rats.
The small intestine (SI) is the main site for food absorption and glutamine utilization hence critical in metabolic disorders that involve energy balance such as diabetes and obesity. This study aims to assess the effects of a known hypoglycaemic compound, oleanolic acid (OA), on some enzymes of glutamine metabolism as well as morphological changes in the SI of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 and 40 mg/kg body weight streptozotocin for type 1 diabetes (T1D) and T2D respectively. One week later, different groups of the diabetic rats were treated with OA, insulin or OA + insulin in the T1D study and OA or metformin for T2D. Untreated diabetic groups served as controls and non-diabetic rats were grouped and treated similarly. After 2 weeks of treatment, all the animals were euthanized and the SI was differently processed for histological and enzymatic studies. The results in both studies indicate significant (p<0.05) increase in the size of the SI and villi in the diabetic compared to the non-diabetic groups and these were not ameliorated by all treatments. The results suggest that treatment with OA increases villi size independent of diabetes. On the other hand, the activity of phosphate dependent glutaminase (PDG) was slightly decreased only in T1D and this was not reversed by treatments. Expression of PDG detected by dot blots was not different in all groups. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GDH) were significantly (p<0.05) elevated in diabetic control groups compared to normal controls and all treatments decreased ALT and AST activities while only insulin decreased GDH activity. Furthermore, hexokinase activity was elevated by diabetes and OA induces further increase. It is concluded that in the early stages of diabetes, OA treatment does not adversely affect PDG activity or expression in the SI but affects other enzymes important in energy metabolism in this tissue.