Phikelelani Ngubane

The Effects of Syzygium aromaticum-Derived Oleanolic Acid on Glycogenic Enzymes in Streptozotocin-Induced Diabetic Rats

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 STZ-induced 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.

Transdermal delivery of insulin by amidated pectin hydrogel matrix patch in streptozotocin-induced diabetic rats: effects on some selected metabolic parameters

Purpose Studies 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. Methods Oral 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. Results After 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. Conclusions The data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin. Novelty of the Work A new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported.

The effects of transdermal insulin treatment of streptozotocin-induced diabetic rats on kidney function and renal expression of glucose transporters

Abstract The tight glycemic control required to attenuate chronic complications in type 1 diabetes mellitus requires multiple daily injections of bolus insulin which cause hyperinsulinemic edema and hypertension due to Na+ retention. Reports indicate that pectin insulin (PI)-containing dermal patches sustain controlled insulin release into the bloodstream of streptozotocin (STZ)-induced diabetic rats. This study investigated whether PI dermal patches can improve the impaired renal function in diabetes. PI patches were prepared by dissolving pectin/insulin in deionized water and solidified with CaCl2. Short-term (five weeks) effects of thrice daily treatments with PI patches on renal function and urinary glucose outputs were assessed in diabetic animals. Blood and kidney samples were collected after five weeks for measurements of selected biochemical parameters. Blood was also collected for insulin measurement 6 h following treatments. The low plasma insulin concentrations exhibited by STZ-induced diabetic rats were elevated by the application of insulin-containing dermal patches to levels comparable with control non-diabetic rats. Untreated STZ-induced diabetic rats exhibited elevated urinary glucose, K+ outputs and depressed urinary Na+ outputs throughout the 5-week period. Treatment with PI dermal patches increased urinary Na+ output and reduced urine flow, urinary glucose and K+ excretion rates in weeks 4 and 5. PI dermal patches increased GFR of diabetic rats with concomitant reduction of plasma creatinine concentrations. Transdermal insulin treatment also decreased the renal expressions of GLUT1 and SGLT1 of STZ-induced diabetic rats. We conclude that PI dermal patches deliver physiologically relevant amounts of insulin that can improve kidney function in diabetes.

The Effects of Plant-Derived Oleanolic Acid on Selected Parameters of Glucose Homeostasis in a Diet-Induced Pre-Diabetic Rat Model

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.

Cardio-protective effects of pectin-insulin patch in streptozotocin-induced diabetic rats Beneficial effects of insulin patch

Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus. Despite the beneficial effects of subcutaneous insulin, reports suggest that the therapy itself precipitates cardiovascular risks due to the high insulin concentration administered. It is therefore necessary to seek alternative routes of insulin administration that may bypass the undesirable effects associated with high plasma insulin concentrations. Accordingly, the present study investigated the effects of a novel transdermal pectin–insulin patch on selected markers of cardiovascular function in diabetes.

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

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.

The Effects of Momordica balsamina Methanolic Extract on Kidney Function in STZ-Induced Diabetic Rats: Effects on Selected Metabolic Markers

Background Studies suggest that Momordica balsamina (intshungu) possesses hypoglycaemic effects. The effects of Momordica balsamina on diabetic complications such as DN, however, have not been established. Accordingly, this study seeks to investigate the effects of M. balsamina on kidney function in STZ-induced diabetic rats. Methods Methanolic extracts (ME) of M. balsaminas leaves were used in this study. Short-term effects of M. balsamina methanolic extract on kidney function and MAP were studied in STZ-induced diabetic rats treated twice daily with M. balsamina methanolic extract (250 mg/kg), insulin (175 μg/kg, s.c.), and metformin (500 mg/kg) for 5 weeks. Results M. balsamina methanolic extract significantly increased Na+ excretion outputs in STZ-induced diabetic rats by comparison to STZ-diabetic control rats. M. balsamina methanolic extract significantly increased GFR in STZ-diabetic rats with a concomitant decrease in creatinine concentration and also reduced kidney-to-body ratio, albumin excretion rate (AER), and albumin creatinine ratio (ACR). M. balsamina methanolic extract significantly reduced MAP in STZ-diabetic animals by comparison with STZ-diabetic control animals. These results suggest that M. balsamina methanolic extract not only lowers blood glucose but also has beneficial effects on kidney function and blood pressure. Conclusion These findings suggest that M. balsamina may have beneficial effects on some processes that are associated with renal derangement in STZ-induced diabetic rats.

The Ameliorative Effect of Pectin-Insulin Patch On Renal Injury in Streptozotocin-Induced Diabetic Rats

Background/Aims: Renal damage and dysfunction is attributed to sustained hyperglycaemia in overt diabetes. Subcutaneous insulin injections are beneficial in delaying the progression of renal dysfunction and damage in diabetics. However, the current mode of administration is associated with severe undesirable effects. In this study, we evaluated the ameliorative effects of pectin-insulin dermal patches on renal dysfunction in diabetes. Methods: Pectin-insulin patches (20.0, 40.8 and 82.9 µg/kg) were applied on the skin of streptozotocin-induced diabetic rats, thrice daily for 5 weeks. Blood glucose concentration, blood pressure and urine output volume were recorded on week 5 after which the animals were sacrificed after which the kidneys and plasma were collected. Kidney nephrin expression and urinary nephrin concentration, albumin excretion rate (AER), creatinine clearance (CC) and albumin creatinine ratio (ACR) were assessed. Results: Patch application resulted in reduced blood glucose concentration and blood pressure. Furthermore, pectin-insulin patch treatment resulted in increased kidney nephrin expression and reduced urinary nephrin concentration. AER, CC ACR were also reduced post patch application. Conclusions: The application of pectin-insulin patch limited diabetes associated kidney damaged and improved kidney function. These observations suggest that pectin-insulin patches may ameliorate kidney dysfunction that is associated with chronic subcutaneous insulin administration.