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.

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.

Diabetes is a serious condition that affects all the body’s systems including kidneys, heart, eyes and limbs. This alone makes type II diabetes a life threatening disease; an expensive disease and economic burden that many individuals struggle to cope with.The rapid growth type II diabetes in South Africa is associated with the change of life style, and environmental factors brought by westernized way of life living in rural areas. Despite the technical advances in diagnosis and therapy of diabetes many people still use alternative forms of therapy due to the cost, traditional reasons and religion. Some of the people use the conventional medication together with the alternative therapy without informing their doctor and knowing the pathological changes. The aim of the study was to investigate pathological changes in male Wistar rats after co-treatment of type II diabetes with metformin and Sutherlandia frutescens and the possible synergistic and antagonistic effects. The thirty five rats were divided into five groups, seven in each group. There were two control groups and three test groups. Only the first control group was on a low fat diet (normal rat pellets) and second control group and test groups were on a high fat diet which induces obesity, insulin resistance and leads a typical prediabetic state for 12 weeks (Buettner et al., 2006). After 11.5 weeks medication was administered by oral gavaging to the test groups for 4 weeks and control groups received water. Blood was collected for determination of glucose, insulin, lipid profile and the concentrations of the liver enzymes. Pancreas, liver and kidney tissue were removed and used for histology. Urine was collected from the bladder for creatinine analyses. The plant + metformin group co-treatment was better in managing hyperglycemia, liver damages were minimal and also weight control was better when compared to metformin alone.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Type 2 diabetes involves defects in glucose-stimulated insulin secretion (GSIS) from the pancreatic beta cells in combination with defects in peripheral (muscle and adipose) tissue glucose uptake. Both GSIS and glucose uptake are regulated by Syntaxin 4 (Syn4)-Munc18c complexes. Importantly, reports link obesity and Type 2 diabetes in humans with changes in protein levels of Munc18c and Syn4; yet the molecular mechanisms underlying this requirement remain unclear. The central hypothesis proposed is that Syn4-Munc18c complexes are modulated by post-translational modifications and novel interactions. Toward this, we found that Syn4-Munc18c complexes are regulated by tyrosine phosphorylation of Munc18c at Y219 in beta cells. Munc18c tyrosine phosphorylation disrupts Syn4-Munc18c complexes, which leads to an increase in Munc18c associating with the double C2 domain protein Doc2β. Disruption of Syn4-Munc18c upon tyrosine phosphorylation results in an increase in Syn4-SNARE complex formation and GSIS from beta cells. Similarly, tyrosine phosphorylation of Munc18c at Y219 and also Y521, disrupts its association with Syn4 in insulin-stimulated 3T3L1 adipocytes and skeletal muscle. In vitro kinase assays further suggested that the insulin receptor tyrosine kinase targeted Y521 of Munc18c. Further investigations using 3T3L1 adipocytes and skeletal muscle extracts indicate that Munc18c interacts with the insulin receptor tyrosine kinase in an insulin-dependent manner, resulting in phosphorylation of Munc18c, coordinate with the timing of its dissociation from Syn4. Finally, we found that stimulus-induced changes occurred also with Syn4, most notably in the islet beta cells. Syn4-mediated insulin release requires F-actin remodeling to mobilize insulin granules to the plasma membrane. Our studies reveal that Syn4 directly associates with F-actin in MIN6 beta cells, and that the disruption of this complex correlates with increases in glucose-stimulated insulin secretion. Future studies will focus upon the potential link between Syn4, F-actin remodeling with Munc18c, to further gain understanding of the requirements for Syn4-Munc18c complexes in insulin secretion. In sum, given the parallels of Munc18c tyrosine phosphorylation in regulating Syn4-Munc18c interaction and exocytosis in beta cells and peripheral tissues, manipulations of this complex may have therapeutic potential as a strategy to treat Type 2 diabetes.

This study was undertaken to determine whether immunoreactive atrial natriuretic peptide (irANP) concentrations in plasma and atrial tissue are altered in experimental diabetes mellitus (DM), and to compare the response of the DM and normal groups to exogenous administration of ANP. OM was induced by intraperitoneal injection of 45 mg/kg streptozotocin in male Sprague-Dawley rats. After three weeks of established OM (glucosuria and blood glucose> 250 mg/dl), plasma irANP levels were 149.6 ± 19.4 pg/ml in the OM group (n = 18) and 86.3 + 12.9 pg/ml in the normal group en = 12, P <0.01). Atrial tissue irANP levels were significantly lower in the OM group (38.1 ± 7.8 ng/mg, n = 7) than in the normal group (60.1 ± 1.3 ng/mg, n = 4, P < 0.02). In response to intravenous infusion of ANP (2.5 ug/kg prime, followed by 0.1 ug/kg/min for 30 minutes), urine flow rate and urine sodium and potassium excretion rates increased significantly in the normal group (n = 6, P < 0.05), while no significant responses were found in the OM group (n = 6). It is concluded that plasma levels of ANP are significantly elevated in streptozotocin-induced diabetes in rats, and that atrial tissue stores are significantly depleted in this diabetic model. In addition, the renal response to exogenously administered ANP appears to be diminished in streptozotocin-induced OM. / Master of Science

Diabetes affects 25.8 million Americans. Complications related to this growing disease impact public health. One secondary complication of diabetes is changes in skin that can contribute to an increased risk for ulceration. Skin of people with diabetes has not been characterized over time nor has the skin’s acute response to exercise been assessed. The objective of this project was to establish the changes in skin properties over time, within different ambient environments, and after acute exercise. This objective sought to address the central hypothesis that skin will demonstrate decreased stiffness and increased elasticity as a result of acute physical activity. Skin stiffness, compliance, and thickness measurements of the plantar foot were compared across time and environment. Skin stiffness and compliance were also compared before and after treadmill walking. First, three devices were validated. Accuracy of the StepWatch was validated for people using assistive devices. The tissue interrogation device (TID), a novel device that measures tangential skin stiffness, and the myotonometer, which measures skin compliance, were validated using elastomer phantoms. Both were found suitable to measure plantar skin properties. Second, skin properties of 16 persons with and without diabetes were measured over time and environmental condition. Skin was variable across subjects over time, but was stable within subjects over a month, supporting the use of a repeated measures approach to interventional study on the plantar skin in people with diabetes. Previous findings for general skin characteristics were supported including the tendency for persons with diabetes to have a thinner epidermis and a thicker dermis than persons without diabetes. Tangential skin stiffness was determined to be less stiff in people with diabetes when measured in a medial-lateral direction. People with diabetes had lower tissue compliance than those without. Skin properties varied across environmental condition, supporting the consideration of testing environment when evaluating skin. Finally, changes in skin properties were evaluated in 32 persons with diabetes before and after treadmill (TM) walking. Using the TID, skin stiffness (tangential) at the great toe of people with diabetes (663.705±4.796 N/m) and without (647.753±5.328 N/m) were different (p=0.040). Stiffness immediately following TM walking did not differ from pre-walking stiffness, but subsequent trials had increased stiffness. Similar, but not significant responses were noted at the first metatarsal head. Compliance using normal loading increased after walking with statistical differences lasting 30-60 minutes.

No description available.

Diabetes mellitus is a chronic disease affecting millions of people worldwide. The degenerative changes caused by diabetes can, however, be controlled through the correct treatment. The outcome of diabetes mellitus depends mainly on the patient's self-management. Health professionals therefore have a major responsibility to assist patients to acquire the essential knowledge, skills and attitudes for self-management. The purpose of this study was to identify diabetic patients and family members' knowledge and views about diabetes mellitus and its treatment regimen. A quantitative descriptive survey design was used. Questionnaires were used to collect data from a convenient sample of diabetic patients and family members. Data was analysed by a computer program called Statistical Package for Social Sciences. Findings revealed that patients and family members lack adequate knowledge on diabetes mellitus and its treatment. Recommendations regarding the required information and assistance to be given to diabetic patients and their family members were formulated. / Health Studies / (MA (Health Studies))

Diabetes mellitus is a chronic disease affecting millions of people worldwide. The degenerative changes caused by diabetes can, however, be controlled through the correct treatment. The outcome of diabetes mellitus depends mainly on the patient's self-management. Health professionals therefore have a major responsibility to assist patients to acquire the essential knowledge, skills and attitudes for self-management. The purpose of this study was to identify diabetic patients and family members' knowledge and views about diabetes mellitus and its treatment regimen. A quantitative descriptive survey design was used. Questionnaires were used to collect data from a convenient sample of diabetic patients and family members. Data was analysed by a computer program called Statistical Package for Social Sciences. Findings revealed that patients and family members lack adequate knowledge on diabetes mellitus and its treatment. Recommendations regarding the required information and assistance to be given to diabetic patients and their family members were formulated. / Health Studies / (MA (Health Studies))