The glucose toxicity has been recognized over the last several years as a factor contributing to both impaired insulin secretion and insulin resistance in patients with diabetes. However, the molecular mechanisms that underlie the changes in glucose transport activity induced by hyperglycemia have not been fully understood. The purpose of the present investigation is to determine if acute hyperglycemia affects an activation of glucose transport and also if hyperglycemic-induced change in insulinstimulated glucose transport is mediated via a PKC-dependent signaling system. Animals were anesthetized, and the soleus (SOL) muscles were isolated and clamped at their resting length. After a 10 minute recovery period the muscles were transferred to preincubation vials containing KHB supplemented with 4 or 16 mmol of glucose and 16 mmol/1 mannitol with or without insulin and/or inhibitors for 30 minutes. Following an incubation series to prepare the muscle, the muscle was incubated in radioactive 3-0- [3H] methylglucose and [14C] mannitol for 10 min. in the presence/absence of insulin and inhibitors, and the amount of glucose transport was measured. A total of 100µU/ml insulin with 4 mM glucose led to increase glucose transport by 155%, whereas the same amount of insulin with 16 MM glucose led to 80% increment in glucose transport. Also, 16 mM glucose in the absence of insulin induced an increase of glucose uptake by apporoximately 50% compared with 4 MM glucose. However, the addition of insulin reduced that difference to 5.3%. The conventional PKC inhibitor GF 109203X in the muscle incubated with 16 MM glucose led to a decrease in insulin-stimulated glucose transport (1l%), whereas the inhibitor with 4 mM glucose induced a decrease in insulin-stimulated glucose transport (24%). These findings suggest that glucose can directly regulate glucose transport activity by a mechanism that possibly involves a facilitated GLUT1 transporter activity. In addition to the mass action of glucose, the hyperglycemic-induced increase in insulin stimulated glucose transport may be partially mediated via a PKC-dependent signaling system. / School of Physical Education

M.Tech. / Impaired glucose tolerance, as determined by an oral glucose tolerance test, is the inability of the blood glucose regulatory mechanisms in the body to return the blood glucose levels to normal physiological levels after the ingestion of a meal (Guyton and Hall, 2006). Mollentze and Levitt (2006) report on various studies that were conducted in South Africa on the prevalence of impaired glucose tolerance and diabetes mellitus and they illustrate that there is an incidence of impaired glucose tolerance as high as 10.2% in certain communities and that impaired glucose tolerance may result in diabetes mellitus. A study has shown that cinnamon controls blood sugar levels by increasing insulin sensitivity resulting in better blood sugar level control (Jarvill-Taylor et al, 2001). The above research was done on cinnamon in the crude form but there is no research on Cinnamomum verum in a homoeopathic potency. The aim of the research was to evaluate the effect of Cinnamomum verum 1X on glucose tolerance in non-diabetic males after an oral glucose tolerance test. A double-blind pre-test post-test placebo controlled study on thirty healthy adult males between the ages of eighteen and forty years was conducted. The participants were recruited by means of an advertisement at the University of Johannesburg Health Clinic. Inclusion criteria comprised: no medication for one month prior to the study with a normal fasting blood sugar level of more than 3.0 but less than 6.0 mmol/l (Oussama, 2006); systolic blood pressure between 100 and 140 mmHg and diastolic blood pressure between 70 and 90 mmHg. At the first consultation the participant data was obtained and an oral glucose tolerance test was performed. The participants were issued with 100 ml of either Cinnamomum verum 1X or a placebo and a weekly checklist to complete. After two weeks the participant data was recorded again and the oral glucose tolerance test was repeated. The Mann-Whitney U-test was used to analyse between the group data statistically and the Wilcoxon Signed-Rank test was used to perform the within-group analysis. The mean fasting blood glucose level of the experiment group changed from 4.71 mmol/l to 4.49 mmol/l. This was a statistically significant reduction, p = 0.025 (< 0.05). The reduction in the blood glucose level after the oral glucose tolerance test of the experiment group was also found to be statistically significant, p = 0.001 (< 0.05) with the mean value changing from 5.86 mmol/l to 5.40 mmol/l. It was concluded that the homoeopathic remedy, Cinnamomum verum 1X taken orally twice daily, was more effective than the placebo in reducing the fasting blood glucose level and the blood glucose level after an oral glucose tolerance test in non-diabetic males between the ages of eighteen and forty years with normal initial fasting blood glucose levels within a time period of two weeks.

Thesis (MPH.) -- University of Limpopo, 2014 / Objective: The purpose of this study was to determine the prevalence of impaired glucose tolerance, impaired fasting glucose, undiagnosed type 2 diabetes and its associated risk factors among adults patients attending the outpatient department of a level one hospital in a rural community of Barkley West, South Africa. Research methodology: This was a cross-sectional survey conducted by a simple random sampling of adults patients F 30 years old. Patients were screened using the American Diabetes Association and the World Health Organisation criteria. First, patients underwent the 75g oral glucose tolerance test and secondly, the 12-hours fasting plasma glucose tests after pre-test results of 5.5 mmol/L were obtained considered as positive for screening. To determine the prevalence of IGT, IFG, and undiagnosed type 2 diabetes; tests were conducted using both the capillary finger puncture and the laboratory methods. To ensure validity and reliability, each patient underwent two tests (fasting and random) by the capillary finger puncture method and two tests (fasting and random) by the laboratory method. Results: Eighty-five (85) questionnaires were distributed, supervised and returned by a research assistant, which brought the response rate to 100%. All patient known living with diabetes mellitus was not included in the study. The prevalence of IGT was 34.1% [34% for females and 9.4% for males] and that for IFG was 23.6% [25% for females and 6.0% for males]. The prevalence of undiagnosed type 2 diabetes discovered during the survey was 9.3% by 2-hours 75g glucose tolerance test [8.2% for females and 1.1% for males] and that by 12-hours fasting plasma glucose, the prevalence was 5.8% [4.7% for females and 1.1% for males].The associated risk factors were physical inactivity, overweight and obesity, unhealthy diet, alcohol consumption, hypertension, smoking habit, family history of diabetes, social deprivation and poverty. The prevalence of hyperglycaemia was also high among female patients due to a higher BMI with 25% overweight (females 18% overweight, males 7% overweight) and 75% obese (females 54% of obesity, males 21% of obesity); higher waist circumference with higher abdominal fat (females 71.7% had a W/C F 88 cm, males 28% had a W/C F 102 cm.); and a larger waist-to-hip ratio (females 61.1% had WHR > 0.85, males 7% had a WHR > 1.0). The sensitivity, specificity, positive and negative predictive values for IGT were 34%, 86%, 25%, and 86% and those for IFG were 24%, 86%, 19%, and 86% respectively. IGT sensitivity was greater than IFG sensitivity. xi Conclusion: There was a high prevalence of IGT, IFG and undiagnosed type 2 diabetes specifically among female patients. The ten percent difference of sensitivity between the two tests showed that the WHO diagnostic criteria produced more patients with the pathology than the ADA diagnostic criteria do. Patients attending the outpatient department of a level one hospital in Barkley West are at high risk of developing type 2 diabetes and remain unidentified, undetected, unscreened, undiagnosed and untreated. Obesity at primary health care level in the rural community of Barkley West needs to be addressed. . Keywords: Impaired glucose tolerance, prevalence, diabetes, screening, anthropometric measurements

Indiana University-Purdue University Indianapolis (IUPUI) / Glucose homeostasis is maintained through the coordinated actions of insulin secretion from pancreatic beta cells and insulin action in peripheral tissues. Dysfunction of insulin action yields insulin resistance, and when coupled with altered insulin secretion, results in type 2 diabetes (T2D). Exocytosis of intracellular vesicles, such as insulin granules and glucose transporter (GLUT4) vesicles is carried out by similar SNARE (soluble NSF attachment receptor) protein isoforms and Munc18 proteins. An additional regulatory protein, Doc2b, was implicated in the regulation of these particular exocytosis events in clonal cell lines, but relevance of Doc2b in the maintenance of whole body glucose homeostasis in vivo remained unknown. The objective of my doctoral work was to delineate the mechanisms underlying regulation of insulin secretion and glucose uptake by Doc2b in effort to identify new therapeutic targets within these processes for the prevention and/or treatment of T2D. Towards this, mice deficient in Doc2b (Doc2b-/- knockout mice) were assessed for in vivo alterations in glucose homeostasis. Doc2b knockout mice were highly susceptible to preclinical T2D, exhibiting significant whole-body glucose intolerance related to insulin secretion insufficiency as well as peripheral insulin resistance. These phenotypic defects were accounted for by defects in assembly of SNARE complexes. Having determined that Doc2b was required in the control over whole body glycemia in vivo, whether Doc2b is also limiting for these mechanisms in vivo was examined. To study this, novel Doc2b transgenic (Tg) mice were engineered to express ~3 fold more Doc2b exclusively in pancreas, skeletal muscle and fat tissues. Compared to normal littermate mice, Doc2b Tg mice had improved glucose tolerance, related to concurrent enhancements in insulin mumsecretion from beta cells and insulin-stimulated glucose uptake in the skeletal muscle. At the molecular level, Doc2b overexpression promoted SNARE complex assembly, increasing exocytotic capacities in both cellular processes. These results unveiled the concept that intentional elevation of Doc2b could provide a means of mitigating two primary aberrations underlying T2D development.