Cette etude pilote de six mois examinait si l'autogestion (AG) intensive par un agent secreteur d'insuline avait pour consequence une glycemie amelioree en comparaison avec une gestion standard (GS) chez les individus atteints de diabete de type 2. Des patients ont ete randomises soit a l'AG avec du repaglinide (n=8), ou du glyburide (n=6) ou a la GS (n=5). Des analyses biochimiques, alimentaires, comportementales, et d'activite physique ont ete effectuees. Les deux groupes de l'AG ont recu un enseignement d'autogestion en fonction du taux de glucose sanguin et une evaluation nutritionnelle qualitative. Le groupe AG (n=11) a suivi la cedule 65% du temps et a fait des ajustements 29% du temps. Une relation inverse significative a ete trouvee entre le changement de l'Alc et le pourcentage de temps d'ajustements accomplis correctement (r=0.64, p=0.035). La difference de masse corporelle entre l'AG et la GS n'etait pas significative, tout comme la masse corporelle moyenne a six mois. Une recherche plus approfondie avec un echantillon de plus grande taille serait necessaire afin d'explorer les avantages potentiels de la gestion du diabete via l'autogestion de medicaments oraux.

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Type 2 diabetes mellitus (T2DM) is often characterized with hyperglycemia, delayed gastric emptying time and a blunted response of gut hormones during feeding that may modulate hunger and satiety. We hypothesized that poor diabetes control is associated with greater hunger suppression, satiation and satiety than good control. We studied 9 T2DM men, after an overnight fast and in response to a 689 kcal mixed meal, twice with or without oral antihyperglycemic agents in a crossover design. Untreated, subjects had higher fasting and postprandial glucose, showed prolonged gastric emptying time and higher thermic effect of food; all factors associated with hunger suppression. Treated, glycemia decreased by 24% and postprandially GLP-1 and PYY3-36 , peptides associated with hunger suppression, were higher than without medication. Thus, no differences were observed in satiation scores between studies. However food intake from a buffet offered 5 hours post meal, an index of satiety, related to hunger scores only in the study with medication.

Although insulin resistance of glucose and fat metabolism in type 2 diabetes mellitus (T2DM) is firmly established, that of protein remains controversial for methodological reasons. A hyperinsulinemic (40MU/m2·min) euglycemic (5.5 mmol/L) isoaminoacidemic (postabsorptive concentrations) clamp was combined with [3-3H]glucose and [1-13C]leucine kinetics to concurrently assess protein and glucose metabolism in 10 hyperglycemic men with T2DM and 11 men without (all BMI=29+/-kg/m2), matched also for age, body composition, and waist circumference. In response to hyperinsulinemia, protein turnover and synthesis were stimulated in controls, but not in T2DM. Both insulin-stimulated total and non-oxidative glucose disposal were diminished in T2DM vs. controls. There was a robust positive correlation between the change in synthesis and glucose disposal. Hence, there is an additive effect of T2DM, beyond that of having excess fat, on insulin resistance of whole body protein turnover and synthesis. Furthermore, protein sensitivity to insulin parallels that of glucose, establishing this as an important concern in T2DM management.

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Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2017. / The continued use and popularity of plant-based traditional medicine demands scientific validation of the therapeutic potential of the medicinal plants used in disease management and treatment. These medicinal plants are to be evaluated for phytochemical constituents and pharmacologically screened for their bioactivity and include the isolation and identification of their bioactive compounds. The diabetes tea and its eight individual plants constituents were collected from Sing Fefur Herbs in McGregor, Western Cape. The plant material was ground to a fine powder form using a milling machine. The powdered plant material was sequentially extracted with hexane, 1:1 DCM, DCM:MeOH, MeOH and water. The antioxidant activity of the tea and its plants was evaluated with comparison to the antioxidant activity of brewed rooibos tea in literature. The concentration of antioxidants in the plants and the tea were found to be significantly high. The ORAC assay results of the water extracts were significantly higher than that of rooibos tea in all plants. Salvia africana-caerulea water extract ORAC results were 14147.10±1.02 μmol TE/g and this is 10 times better than the brewed rooibos tea results of 1402±44.1 μmol TE/g. The alpha-amylase enzyme inhibition assay showed no significant results while the alpha-glucosidase enzyme inhibition assays showed significant results in some of the extracts. The highest inhibitory activity towards alpha-glucosidase was found in the Urtica urens hexane extract and the Thymus vulgaris hexane extract (69.66% and 68.43%, respectively). This observation suggests that alpha-glucosidase enzyme is inhibited mostly by the less polar or medium polarity chemical components of the plant extracts. The crude plant extracts that showed significant activity in the antidiabetic bioassays were further subjected to cytotoxicity assay to ascertain the safety of extracts. The T. vulgaris DCM extract, Salvia officinalis DCM extract and Salvia officinalis hexane extract showed a cell growth inhibition of 54.91%, 62.14% and 63.87% at 100 μg/ml, respectively. The Salvia africana-caerulea DCM extract showed a cell growth inhibition of 59.10% at 50 μg/ml and 62.14% at 100 μg/ml. In the cytotoxicity analysis Salvia africana-caerulea DCM extract is the only extract that showed cell viability below 50% for both concentrations. Phytochemical screening of selected methanolic and aqueous extracts of the diabetes tea and the Salvia africana-caerulea showed the presence of alkaloids, sugars, flavonoids, glycosides, proteins & amino acids, phenolics & tannins and saponins. Furthermore isolation, purification and analysis of two Salvia africana-caerulea crude extracts (DCM and DCM:MeOH) were done in order to try and obtain pure compounds. The compound characterization was done through the use of chromatographic techniques. Thin layer chromatography (TLC), flash chromatography and column chromatography resulted in the generation of 29 fractions. Spectroscopic techniques utilized for chemical structural elucidation for compounds of interest included Liquid chromatography mass spectrometry and Nuclear Magnetic Resonance Spectroscopy. Of all the fractions generated, DM 23 was the purest and its structural elucidation was attempted.

In Africa, non-communicable diseases such as diabetes mellitus have been generally neglected. This problem has worsened over the years owing to continuous threats from infectious diseases such as HIV/AIDS, tuberculosis and malaria. Despite this, statistics have shown that by 2030, the African region will have the highest proportional increase in diabetes prevalence. Over 80% of all diabetic deaths occur in developing countries probably not only due to poor equity of access to medication but also due to limited efficacy and side effects associated with the commonly available anti-diabetic agents. Therefore, this creates the desperate need for the development of new anti-diabetic agents that are more efficacious and can be sourced from within the continent. With oxidative stress as a suggested mechanism underlying the cause of diabetes mellitus and diabetic complications, the discovery of natural anti-oxidants that prevent free radical mediated damage is important for developing new treatment strategies. Marine algae have been identified as good sources for natural anti-oxidants. Unfortunately, very few studies have embarked on the discovery of marine-derived anti-oxidant compounds with potential anti-diabetic activity. In this project, we investigated the potential anti-oxidant activity of the South African endemic algae Stypopodium multipartitum, Dictyopterus ligulata, Cystophora fibriosa, Bifurcariopsis capensis, Sargassum sp. and Sargassum heterophyllum. From these studies, Sargassum heterophyllum yielded prenylated compounds, the main compound being sargahydroquinoic acid (3.6) and the carotenoid metabolite fucoxanthin (3.8), which are in part responsible for the radical scavenging activity of the crude extract. Sargahydroquinoic acid (3.6) and fucoxanthin (3.8) also exhibited significant anti-inflammatory activity. Sargaquinoic acid (3.1), sargachromenoic acid (3.9) and sarganaphthoquinoic acid (3.10) were then semi-synthesized from sargahydroquinoic acid (3.6) and their in-vitro cytotoxicity profiles evaluated using Chang Liver, HT-29, Caco-2 and 3T3-L1 cell lines prior to antidiabetic testing. From the semi-synthetic derivatives, sargachromenoic acid (3.9) exhibited the most potent anti-oxidant activity (IC₅₀ = 6.99 μg/mL). After the evaluation of antidiabetic activity using 3T3-L1 preadipocyte differentiation, sarganaphthoquinoic acid (3.10) showed the most potent insulinomimetic activity at 1.19 μM by inducing a PPARγ response similar to that of rosiglitazone at 1 μM.

Diabetes mellitus has been associated with both clinical and experimental cardiac dysfunction. Diabetic cardiomyopathy which is characterized by depressed cardiac contractility is accompanied by a variety of biochemical changes in Ca⁺⁺ metabolism. This cardiomyopathy may occur in the presence of normal coronary arteries and normal blood pressure. However, some studies have shown that hypertension is more prevalent among diabetics and can aggravate the cardiovascular abnormalities associated with diabetes. To understand the mechanisms of diabetic cardiomyopathy and consequences of combined hypertension and diabetes, experiments were designed to measure cardiac tissue responses to various inotropic agents in experimental diabetes. Six weeks following streptozotocin (STZ) administration, Wistar, spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats exhibited the 'classical signs' of diabetes which included: hyperglycemia, hypoinsulinemia, hyperlipidemia (except in WKY), and hypothyroidism. Decreased basal atrial rate and increased basal developed force (BDF) suggest a depressed SA node function and an alteration of Ca⁺⁺ utilization by diabetic ventricles. Decreased post quiescent potentiation (PQP) values (except in WKY) in ventricular tissues suggest a diminished amount of releasable Ca⁺⁺ from sarcoplasmic reticulum (SR). Decreased post stimulation potentiation (PSP) values in SHR papillary muscles (PM) are probably suggestive of a depressed sarcolemmal Na⁺-Ca⁺⁺ exchange function in this tissue. Diabetic rats show subsensitivity to β-adrenergic stimulation in ventricular tissues, supersensitivity and hyperresponsiveness to Ca⁺⁺ and α-adrenergic stimulation (except in WKY) in ventricular tissues and left atria (LA) and supersensitivity to BAY K 8644 in SHR LA and hyperresponsiveness to verapamil in ventricular strips. These alterations may be attributed to a change in receptor number and/or a post receptor alteration. Ryanodine decreased the PQP of Wistar and SHR PM and SHR LA in both controls and diabetics. It especially abolished PQP in SHR diabetic tissues, but had no effect on WKY tissues, which may suggest a difference in the SR function in these tissues. SR with impaired Ca⁺⁺ uptake may contribute to these phenomena in diabetic rats. Ryanodine also diminished (PQP + BDF) of SHR LA and (PQP/BDF) of Wistar and SHR PM, ˙but had no effects on control and other diabetic tissues. It appears that ryanodine has some influence on the Na⁺-Ca⁺⁺ exchange generated by sarcolemma (SL) of certain diabetic tissues. Further experiments are required to clarify this. SHR diabetic rats had greater changes in most of the measurements such as hyperlipidemia, depressed PQP and PSP values, and altered drug responses. This model exhibited very high mortality as compared to Wistar and WKY diabetic rats. As has been shown previously, the combination of hypertension and diabetes exerts a synergistic effect on the cardiac dysfunction in this model, and that altered lipid metabolism, SL and SR function are all involved in the development of cardiomyopathy. WKY diabetic rats, on the other hand, exhibited no significant changes in blood lipids, or in response to phenylephrine or to Ca⁺⁺ (LA) stimulation. Lack of change in these factors may explain the relatively normal cardiac function of this model as measured previously. / Pharmaceutical Sciences, Faculty of / Graduate