Effects of a Ruthenium Schiff Base Complex on Glucose Homeostasis in Diet-Induced Pre-Diabetic Rats

Abstract

Pre-diabetes is a condition that precedes type 2 diabetes mellitus (T2DM) that is characterised by elevated glycated haemoglobin (HbA1c). The management of pre-diabetes includes the combination of dietary and pharmacological interventions to increase insulin sensitivity. However, poor patient compliance has been reported with regard to dietary interventions, therefore, new alternative drugs are required that can be effective even without the dietary intervention. In our laboratory, we have synthesised a novel ruthenium complex that has been shown to have elevated biological activity. This study investigated the effects of this complex in both the presence and absence of dietary intervention on glucose handling in a diet-induced pre-diabetes rat model. Pre-diabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to pre-diabetic rats once a day every third day for 12 weeks. The administration of the ruthenium complex resulted in reduced fasting blood glucose, food intake, and body weight gain which was associated with decreased plasma ghrelin, insulin, and HbA1c levels in both the presence and absence of dietary intervention. The administration of the ruthenium complex ameliorated glycaemic control and insulin sensitivity in pre-diabetic rats. The results of this study warrant further investigations as this compound could potentially be able to re-sensitize insulin resistant cells and reduce the incidence of T2DM.

<p>Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model</p>

“…46,47 Moreover, OA has also been reported to reduce the risk of developing cardiovascular disease by lowering LDL-C particles while increasing high-density lipoprotein cholesterol (HDL-C) particles. 16,17 These findings correlated with the previous study that reported that derivatives of OA such as 3-acetyl-oleanolic acid have also been shown to lower intrahepatic total cholesterol (TC), TGs and macrovesicular steatosis in high-fat diet-fed rats. 16,18,48 While the observed decrease in plasma TGs and VLDLs may partly be attributed to dietary intervention, it may also be ascribed to the insulinsensitizing effects of OA.…”

“…23 Recent studies in our laboratory have reported that prolonged consumption of a high-fat high-carbohydrate (HFHC) diet leads to the development of prediabetes. 17 This condition is characterized by complications including hypertriglyceridemia, insulin resistance and hyperinsulinemia which are risk factors for the development of NAFLD. 16,24 The conventional management of NAFLD involves the combination of insulin sensitizers and lifestyle modification therapy which include exercise and dietary modification.…”

“…16 Moreover, OA has been reported to improve insulin sensitivity in peripheral organs such as skeletal muscle and thus attenuate hyperglycemia in a pre-diabetic rat model. 17 This lowers the hepatic glucose influx which subsequently results in a decrease in hepatic lipogenesis. 16,32 However, OA + DI had more pronounced effects which may suggest that diet intervention may have also contributed in the reduction of liver weight and total body fat content.…”

“…49,50 A recent study in our laboratory reported that this model of prediabetes has high levels of systemic ROS as a result of lipotoxicity. 17 In addition, augmented FFA influx into the liver is also associated with hepatocyte degeneration including ballooning and inflammation which subsequently lead to non-alcoholic steatohepatitis (NASH). 51 The current findings also demonstrated that during pre-diabetes there is augmented circulating and intrahepatic triglycerides which is directly associated with lipotoxicity and generation of reactive oxygen species (ROS).…”

“…Experimental pre-diabetes was induced in male Sprague-Dawley rats (n=36) using a previously described protocol. [16][17][18] The pre-diabetic animals were further sub-divided into six groups each group having six rats (n=6). The groups were as follows: pre-diabetic control group (PC) which were the prediabetic animals that continued with the experimental diet throughout the study period; metformin group (MET) which were the pre-diabetic animals that continued with the experimental diet but received metformin during treatment period; metformin and diet intervention group (MET + DI) which were the pre-diabetic animals that changed to a normal diet and received metformin during treatment period; oleanolic acid group (OA) which were the pre-diabetic animals that continued with experimental diet but received oleanolic acid during treatment period as well as OA and diet intervention group (OA + DI) which were the pre-diabetic animals that changed to a normal diet and received oleanolic acid during experimental period.…”