Ngubane, Phikelelani Siphosethu.Khathi, Andile.Sibiya, Ntethelelo Hopewell.Khumalo, Bongiwe.2020-09-102020-09-1020202020https://researchspace.ukzn.ac.za/handle/10413/18652Masters Degree. University of KwaZulu-Natal, Durban.Increased consumption of fat and high carbohydrate coincided with increased prevalence in type 2 diabetes, a condition whose onset is always preceded by prediabetes. Prediabetes is best characterised by hyperglycaemia, insulin resistance and glucose intolerance. Prolong chronic hyperglycaemia exacerbates complications of increased oxidative stress, advanced glycation end products (AGE), dyslipidaemia, hyperinsulinemia and increased inflammatory markers. Once diagnosed, life style and dietary interventions strategies are one of the cornerstones in management of prediabetes. However, patients do not adhere to these life style changes. Hence the present study investigated the effects of Momordica balsamina (MB) on glucose handling in insulin resistance in C2C12 palmitic acid induced insulin resistant cell lines and in high fat high carbohydrate induced prediabetic rat model. Methods Briefly, air-dried MB leaves were extracted with methanol to yield methanolic extracts. The study was divided into 2 experimental series invitro, first series investigated the effects of MB compounds on cell viability in skeletal muscle cell lines. The second series investigated the effects of MB on glucose uptake in palmitic acid induced insulin resistant skeletal muscle cell lines. Invivo studies encompassed HFHC-induced diabetic rats which were divided into untreated and treated groups. The rats were treated with metformin (500 mg kg-1 p.o.) as standard drug and MB (250 mg kg-1 p.o.) a test drug. MB (250 mg kg-1 p.o.) was administered once every third day. Blood glucose concentration, body weight and calorie intake were monitored every fourth week for a period of 12 weeks. Terminally, animals were sacrificed after which blood, liver and skeletal muscle were collected for biochemical analysis. Results MB significantly decreased media glucose concentration whilst glycogen concentration was improved by comparison with insulin resistant cells. Treatment with MB reduced tissue damage which was shown MDA in the plasma while also improving their antioxidant status compared with insulin resistant cells. In vivo study, we measured caloric intake, body weights, ghrelin concentration, OGT response, glycogen concentration, GLUT 4, glycogen synthase, HOMA2- IR value and glycated haemoglobin (HbA1c) concentration. Interestingly, Momordica balsamina coupled with dietary intervention resulted in decreased fasting glucose concentration, suggesting improvement in insulin sensitivity. Reduced caloric intake and restored a steady constant weight growth, thus preventing obesity. This was associated with decreased plasma ghrelin levels. Additionally, there was a significant decrease in HOMA2-IR value. This was further evidenced by decreased levels of glycated haemoglobin in the MB-treated rats. Conclusion The results obtained suggests that Momordica balsamina (MB) possesses anti-hyperglycaemic and protective properties in vivo and in vitro, therefore could be potent in the management of prediabetes, impaired glucose homeostasis induced hyperglycaemia. In addition, these findings provide new scope to comprehensively delineate the medicinal plant, Momordica balsamina mechanism of activity.enMomordica balsamina.Induced prediabetic.Impaired glucose homeostasis.Streptozotocin (STZ).Hyperglycaemia.Thesis