- Title
- Development of insulin resistance in a rat model and the effects of sutherlandia frutescens as treatment and prevention
- Creator
- Mackenzie, Janine
- Subject
- Metabolic syndrome
- Subject
- Insulin resistance -- Animal models
- Subject
- Obesity -- Treatment
- Date Issued
- 2010
- Date
- 2010
- Type
- Thesis
- Type
- Doctoral
- Type
- DPhil
- Identifier
- vital:10340
- Identifier
- http://hdl.handle.net/10948/d1016216
- Description
- The global number of obese people has reached pandemic proportions. High caloric diets and reduced physical exercise are to blame for this growing epidemic. Obesity has a very complex association with several other metabolic disorders, such as insulin resistance (IR), diabetes mellitus type 2 (DMT2) and cardiovascular disease. This puts a huge burden on health care systems world wide and claims many lives. Sutherlandia frutescens is a traditionally used herb, which is known to have anti-diabetic properties. However, the direct mode of action of S. frutescens still remains to be elucidated. The aim of this study was to investigate the developmental stages of high fat diet (HFD)-induced IR, to illuminate the pathogenesis of IR with a focal point on modifications in the lipid metabolism. Furthermore, the effects of S. frutescens as a treatment or prevention drug for IR and associated metabolic changes were examined. Two sets of experiments were conducted on male Wistar rats. In the first experiment rats, one week post weaning received a low fat diet (LFD), high fat diet (HFD) or HFD supplemented with S. frutescens (50mg/kg BW/d). Rats were sacrificed at week 0, 1, 2, 4, 8 and 12 in the feeding regime. In a second experiment rats were fed with a LFD or a HFD for 12 weeks and treated thereafter with S. frutescens (50mg/kg BW/d), metformin (13mg/kg BW/d) or water (control) for 28 days. Rats in the second experiment were sacrificed at week 12 to confirm IR while concurrently run rats were sacrificed after 28 days of treatment. For all the experiments rats were anaesthetized, blood was removed and rats were dissected. Plasma samples were analyzed for insulin, glucose, blood lipid parameters and cytokines. Liver, muscle and adipose tissue were analyzed for glucose uptake, total lipid content, lipid profile and fatty acid profile. It was shown that the intake of HFD caused IR and hyperinsulinaemia. The developmental stages in experiment one confirmed that an increase in plasma free fatty acids preceeded the onset of IR. Plasma and tissue lipid parameters (free fatty acid-, triglyceride- and cholesterol concentrations) showed pathological modifications in the HFD group. An ectopic accumulation of fat was observed in muscle and liver, as well as a change in membrane fatty acid profile. The results for circulating cytokines were somewhat inconclusive. Rats supplemented with S. frutescens did not develop HFD-induced IR (study one) or IR was reversed (study two). S. frutescens treatment also resulted in positive changes in plasma and tissue lipid parameters. In summary, an animal model for HFD-induced IR was established and the detrimental effect of elevated plasma FFA on glucose and lipid metabolism was observed. A novel discovery suggests that the anti-diabetic mode of action of S. frutescens is through modulation of lipid metabolism. It was also established that S. frutescens has the potential to prevent IR in vivo.
- Format
- xv, 190 leaves
- Format
- Publisher
- Nelson Mandela Metropolitan University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela Metropolitan University
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NMMU School of BioMolecular and Chemical Sciences
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