Metabolic effects brought about by tricyclic antidepressants and the contribution of a medicinal plant in alleviating high fat diet induced insulin resistance in male wistar rats
- Authors: Chadwick, Wayne
- Date: 2006
- Subjects: Rats -- Metabolism , Diabetes -- Research , Medicinal plants -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10329 , http://hdl.handle.net/10948/461 , Rats -- Metabolism , Diabetes -- Research , Medicinal plants -- South Africa
- Description: Type II diabetes is becoming a growing problem in developed countries worldwide. The median age for diagnosis was around sixty, but recent surveys have shown that the entire age distribution curve shifting left. The incidence of type II diabetes is thought to be parallel with the growing rate of obesity associated with an unhealthy western diet. Type II diabetes is an expensive disease to manage, it is for this reason that cheaper medication needs to be investigated in the form of traditional plants, such as Sutherlandia frutescens. Prescription medication, such as tricyclic antidepressants, may also increase body weight thereby playing a role in obesity. The cause of weight gain in such cases may go unrecognized or lead to cessation of the medication with or without the practitioner’s knowledge or approval. It is therefore necessary to investigate the causative agents responsible for the excessive weight gain. Drinking water containing extracts of S. frutescens or metformin was administered to two groups of eleven insulin resistant male Wistar rats. The insulin resistant control group received water without any medication. Rats were sacrificed after 8 weeks allowing for fasting blood glucose, insulin and tissue glycogen content determination. Glucose uptake was also determined using [3H] deoxyglucose. The effect of the medication and the diet on muscle post receptor insulin signaling proteins was determined through Western blots. Liver proteomics was also performed using 2-D electrophoresis. In a separate experiment 26 male Wistar rats were exposed to strepotozotocin toxin, 7 of these rats received intravenous insulin treatment, 7 rats received S. frutescens extract and 7 rats received a combination of both medications, the remaining 5 received no treatment and served as the control. Rats were sacrificed after 6 days allowing for fasting blood glucose, insulin and tissue glycogen content determination. Two groups of 14 male Wistar rats received amitriptyline or trimipramine (common tricyclic antidepressants) in their drinking water, the control group (30 rats) received water without any medication. The rats’ weight and food consumption was monitored throughout the trial and their oxygen consumption was also determined. Rats were sacrificed after 6 weeks or 14 weeks of medicinal compliance allowing for fasting blood glucose, insulin and tissue glycogen content determination. Glucose uptake was also determined using [3H] deoxyglucose. S. frutescens treatment normalized circulating serum insulin levels and significantly increased the rate of glucose clearance. Certain post receptor insulin signaling proteins were also significantly increased relative to the insulin resistant control group. 2-D electrophoresis identified the normalization of protein levels associated with the urea cycle. S. frutescens was also able to, independently; maintain normoglycaemic levels in the strepotozotocin treated group. The tricyclic antidepressants significantly increased blood glucose levels while significantly reducing tissue glycogen levels for both sacrifice periods. Serum insulin remained unchanged while a significant increase in insulin degradation and insulin degrading enzyme levels were found for both antidepressants. S. frutescens shows promise as a low cost antidiabetic medication for future use. Although the antidepressants did not promote weight gain, the increase in blood glucose levels may be cause for concern in patients with a pre-disposition toward developing diabetes.
- Full Text:
- Date Issued: 2006
Observed metabolic changes in male Wistar rats after treatment with an antidepressant implied in undesirable weight gain, or Sutherlandia frutescens for Type II diabetes
- Authors: Chadwick, Wayne
- Date: 2003
- Subjects: Rats -- Metabolism , Non-insulin-dependent diabetes -- Research , Rats as laboratory animals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:11068 , http://hdl.handle.net/10948/313 , Rats -- Metabolism , Non-insulin-dependent diabetes -- Research , Rats as laboratory animals
- Description: Type II diabetes is fast becoming a growing problem in developed countries worldwide. Traditionally the median age for diagnosis was around sixty, but recent surveys have shown that the entire age distribution curve has shifted to the left. Western countries boast the worst statistics in which type II diabetes is being reported in children under the age of ten. At such a young age the disease often goes undiagnosed for long periods of time allowing considerable damage to occur. The incidence of type II diabetes is thought to be parallel with the growing rate of obesity associated with a characteristically unhealthy western diet. Type II diabetes is an extremely expensive disease to manage, and with the rapid growth of this pandemic our country will soon feel the economic burden of this disease. It is for this reason that cheaper medication needs to be investigated in the form of traditional plants, such as Sutherlandia frutescens. Prescription medication, such as tricyclic antidepressants, may also increase body weight or appetite thereby playing a role in obesity. The cause of weight gain in such cases may go unrecognized or lead to cessation of the medication with or without the practitioner’s knowledge or approval. It is therefore necessary to investigate the causative agents responsible for the excessive weight gain. Drinking water containing extracts of the S. frutescens, metformin (a well known type II diabetes medication) and amitriptyline (a common tricyclic antidepressant) was administered to three groups of ten male Wistar rats. The control group received water without any medication. The rat’s weight and food consumption was monitored throughout the trial and their oxygen consumption was also determined. Rats were sacrificed after four months of medicinal compliance and glucose uptake, in the presence and absence of insulin, was tested in epididymal fat, liver and muscle. Fasting plasma glucose levels, lipoprotein, cholesterol and triglyceride concentrations were also determined.
- Full Text:
- Date Issued: 2003