Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological and dietary interventions is used to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Oleanolic acid (OA) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this compound on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects OA on a diet-induced pre-diabetes rat model. Pre-diabetic male Sprague Dawley rats were treated with OA in both the presence and absence of dietary intervention for a period of 12 weeks. The administration of OA with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, plasma ghrelin concentration and glycated haemoglobin by comparison to the pre-diabetic control. These results suggest that OA may be used to manage pre-diabetes as it was able to restore glucose homeostasis and prevented the progression to overt type 2 diabetes.

The pathogenesis of prediabetes is associated with risk factors such as chronic consumption of an unhealthy diet. Recent studies have reported that diet-induced pre-diabetes is also associated with risk factors of cardiovascular complications, hence this study was aimed at evaluating the effects of oleanolic acid (OA) on pre-diabetes rats. Pre-diabetes was induced by chronic exposure of Sprague Dawley rats (SD) to high-fat high-carbohydrate diet (20 weeks), whereas the non-pre-diabetes control (NC) was given standard rat chow. Pre-diabetes animals were grouped into five groups namely prediabetes control (PC), metformin treated (Met), metformin with diet intervention (Met + DI), oleanolic acid treated (OA), and oleanolic acid with diet intervention (OA + DI) then treated for 12 weeks. At the end of treatment, all animals were sacrificed where organs and tissues were harvested for biochemical analysis and histological studies. The results showed that PC had a significantly higher triglycerides (TGs), low density lipoprotein cholesterol (LDL-C, interleukin-6(IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), mean arterial pressure (MAP) and hearts weights in comparison to NC (p < 0.05). However, the administration of OA, in both the presence and absence of dietary intervention showed a significant decrease in TGs, LDL-C, IL-6, TNFα, CRP, MAP, hearts weights (p < 0.05). In conclusion, the administration of OA was able to lower the risks of developing CVDs in pre-diabetes rat model through ameliorating dyslipidaemia, oxidative stress, hypertension, and low-grade inflammation. Therefore OA has the potential to be used as an alternative treatment to prevent the onset of CVDs during pre-diabetes stage even in the absence of dietary and lifestyle intervention.

PurposeStudies in our laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. We therefore investigated whether the application of pectin insulin (PI)-containing dermal patches of different insulin concentrations sustain controlled release of insulin into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of diabetic symptoms in target tissues, most importantly, muscle and liver.MethodsOral glucose test (OGT) responses to PI dermal matrix patches (2.47, 3.99, 9.57, 16.80 µg/kg) prepared by dissolving pectin/insulin in deionised water and solidified with CaCl2 were monitored in diabetic rats given a glucose load after an 18-h fast. Short-term (5 weeks) metabolic effects were assessed in animals treated thrice daily with PI patches 8 hours apart. Animals treated with drug-free pectin and insulin (175 µg/kg, sc) acted as untreated and treated positive controls, respectively. Blood, muscle and liver samples were collected for measurements of selected biochemical parameters.ResultsAfter 5 weeks, untreated diabetic rats exhibited hyperglycaemia and depleted hepatic and muscle glycogen concentrations. Compared to untreated STZ-induced diabetic animals, OGT responses of diabetic rats transdermally applied PI patches exhibited lower blood glucose levels whilst short-term treatments restored hepatic and muscle glycogen concentrations. Plasma insulin concentrations of untreated diabetic rats were low compared with control non-diabetic rats. All PI treatments elevated plasma insulin concentrations of diabetic rats although the levels induced by high doses (9.57 and 16.80 µg/kg) were greater than those caused by low doses (2.47 and 3.99 µg/kg) but comparable to those in sc insulin treated animals.ConclusionsThe data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin.Novelty of the WorkA new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported.

Studies indicate that the antihyperglycemic effects of Syzygium aromaticum-derived oleanolic acid (OA) are mediated in part through increased hepatic glycogen synthesis. Accordingly, this study assessed the influence of OA on the activity of glucokinase (GK) and hexokinase (HK) of skeletal muscle and liver tissues in streptozotocin (STZ)-induced diabetic rats. After 5 weeks of OA treatment, hepatic and gastrocnemius muscle glycogen concentrations and activities of GK and HK were measured spectrophotometrically in reactions where the oxidation of glucose-6-phosphate (G-6-PDH) formed was coupled to nicotinamide adenine dinucleotide phosphate (NADP + ) reduction catalyzed by G-6-PDH dehydrogenase. Rats treated with deionized water or standard hypoglycemic drugs acted as untreated and treated positive controls, respectively. STZ-induced diabetic rats exhibited depleted glycogen levels and low activities of glycogenic enzymes in muscle and hepatic tissues. OA administration restored these biochemical alterations to near normalcy. The combination of OA and insulin did not significantly alter the activities of HK and GK of STZinduced diabetic rats, suggesting that glycogen synthesis can also occur from precursors such as amino acids or fructose and lactate. The attenuation of the activities of glycogenic enzymes with concomitant increases of hepatic and muscle glycogen concentrations of STZ-induced diabetic rats provides a therapeutic strategy for diabetes treatment.

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