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.

Iatrogenic hypoglycemia is a limiting factor for managing diabetes mellitus and can have severe outcomes such as seizures and coma. Although several studies have investigated the central nervous system consequences of hypoglycemia, the effects of seizures, as well as possible treatment strategies, have yet to be elucidated in juvenile animals. The objective of this thesis was to establish an in vivo model of severe hypoglycemia and seizures in juvenile diabetic and non-diabetic rats. In both groups there existed a similar blood glucose threshold for seizures, and mortality only occurred following severe seizures, particularly with repeated seizures that were unresponsive to treatment. While the administration of anticonvulsants temporarily mitigated seizures, glucose administration was required to prevent mortality. Abnormalities in the hippocampal and brainstem electroencephalograms (EEG) were observed in hypoglycemic animals without a clear correlate to convulsive activity.

Iatrogenic hypoglycemia is a limiting factor for managing diabetes mellitus and can have severe outcomes such as seizures and coma. Although several studies have investigated the central nervous system consequences of hypoglycemia, the effects of seizures, as well as possible treatment strategies, have yet to be elucidated in juvenile animals. The objective of this thesis was to establish an in vivo model of severe hypoglycemia and seizures in juvenile diabetic and non-diabetic rats. In both groups there existed a similar blood glucose threshold for seizures, and mortality only occurred following severe seizures, particularly with repeated seizures that were unresponsive to treatment. While the administration of anticonvulsants temporarily mitigated seizures, glucose administration was required to prevent mortality. Abnormalities in the hippocampal and brainstem electroencephalograms (EEG) were observed in hypoglycemic animals without a clear correlate to convulsive activity.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Ohio University, June, 2004. / Includes bibliographical references (leaves 126-138).

Diabetes mellitus (DM) is a life changing disease which affects a large portion of the population and the economy through high medical costs and loss of productivity. Marrubiin (MAR), a diterpenoid isolated from Leonotis leonurus, a plant indigenous to Southern Africa, is used by traditional healers to alleviate DM symptoms. This study aims to screen the inhibitory potential of MAR and MAR derivatives on PTP1β and glucose uptake properties of Chang liver, C2C12 and 3T3-L1 cells. Marrubiin and 19 of its derivatives were tested to determine the inhibition constants for PTP1β. A Ki of 21 μM and 0.047 μM was detected for oleanolic acid in silico and in vitro, respectively. All other diterpene derivatives did not display substantial levels of inhibition of PTP1β. Treatment of Chang liver cells with the various MAR derivatives (10 μM) did not significantly increase glucose uptake beyond metformin, a known antidiabetic drug. The various treatments showed a protective/proliferative effect on the C2C12 muscle cells with two MAR treatments (DC16 and DC18) significantly increasing glucose uptake as compared to metformin in C2C12 muscle cells. It was noted that DC17, DC18 and MAR significantly increased glucose uptake in 3T3-L1 adipocytes, relative to the control. Contrary to cytotoxicity studies with Chang liver and C2C12 muscle cells, adipocytes displayed no cytotoxicity to treatments while a significant increase in cell viability was seen for DC9 and DC15. To unravel the mechanism of action, Western blotting analysis was completed and an increased expression of PTP1β was observed for treatments with DC17 and DC6 was seen in adipocytes, while DC18 and metformin decreased expression significantly. This correlated with a significant decrease of Ser 612 phosphorylation of insulin receptor substrate (IRS1) for DC17. Real time qPCR of IRS1 and GLUT4 highlighted that DC17 and MAR were able to significantly increase expression of IRS1 and GLUT4, respectively. The results show that MAR and the selected derivatives (DC6, DC17, DC18) have been found to increase glucose uptake in peripheral tissue types with IRS1, GLUT4 and PTP1β being associated with the mechanism of action. However, a complete understanding of the mechanisms is yet to be established.

No description available.

by Li Chi Yeung. / Thesis submitted in: November 2004. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 151-176). / Abstracts in English and Chinese. / Thesis Committee --- p.i / Acknowledgement --- p.ii / Abstract (English Version) --- p.iii / Abstract (Chinese Version) --- p.v / Content Page --- p.vii / List of Tables --- p.xiii / List of Figures --- p.xv / Abbreviation --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Diabetes Mellitus --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.1 / Chapter 1.1.2 --- Economic Impact --- p.3 / Chapter 1.2 --- "Digestion, Absorption and Metabolism of Carbohydrates" --- p.4 / Chapter 1.2.1 --- Carbohydrate Digestion --- p.4 / Chapter 1.2.2 --- Carbohydrate Absorption --- p.6 / Chapter 1.2.3 --- Insulin Secretion --- p.6 / Chapter 1.3 --- Pathophysiology of Diabetes Mellitus --- p.7 / Chapter 1.3.1 --- Insulin-Dependent Diabetes Mellitus (lDDM) --- p.7 / Chapter 1.3.1.1 --- Genetics --- p.8 / Chapter 1.3.1.2 --- Autoimmunity --- p.9 / Chapter 1.3.2 --- Non-Insulin-Dependent Diabetes Mellitus (NlDDM) --- p.11 / Chapter 1.3.2.1 --- Insulin Resistance --- p.11 / Chapter 1.3.2.2 --- Impaired Insulin Secretion --- p.14 / Chapter 1.4 --- Management of Diabetes Mellitus --- p.15 / Chapter 1.4.1 --- Sulfonylureas --- p.15 / Chapter 1.4.2 --- Biguanides --- p.16 / Chapter 1.4.3 --- Problems Encountered in the Management of Diabetes --- p.16 / Chapter 1.4.4 --- Role of Dietary Fiber in the Management of Diabetes Mellitus --- p.18 / Chapter 1.4.4.1 --- Dietary Fiber and Gastric Emptying Time --- p.19 / Chapter 1.4.4.2 --- Dietary Fiber and Glucose Absorption in Small Intestine --- p.20 / Chapter 1.4.5 --- Other Natural Products used for Diabetes Treatment…… --- p.22 / Chapter 1.5 --- Mushrooms --- p.22 / Chapter 1.5.1 --- The Definition of Mushrooms --- p.23 / Chapter 1.5.2 --- Nutritional Values of Mushrooms --- p.24 / Chapter 1.5.3 --- Production of Mushrooms --- p.25 / Chapter 1.6 --- Medicinal (Antidiabetic) Properties of Mushrooms --- p.28 / Chapter 1.6.1 --- Ganoderma lucidum --- p.29 / Chapter 1.6.2 --- Tremella aurantia --- p.33 / Chapter 1.6.3 --- Auricularia auricula --- p.36 / Chapter 1.6.4 --- Grifola frondosa --- p.37 / Chapter 1.7 --- Medicinal Uses of Hericium erinaceus --- p.39 / Chapter 1.7.1 --- HeLa Cell Proliferation Inhibitors --- p.39 / Chapter 1.7.2 --- Induction of Growth of Nerve Cells --- p.42 / Chapter 1.7.3 --- Antitumour Activity --- p.42 / Chapter 1.7.4 --- Antidiabetic Effect --- p.43 / Chapter 1.8 --- Objectives --- p.45 / Chapter Chapter 2 --- Materials and Methods --- p.46 / Chapter 2.1 --- Extraction of Polysaccharides from the Fruiting Body of H. erinaceus --- p.46 / Chapter 2.1.1 --- Small-scale Extraction --- p.46 / Chapter 2.1.2 --- Large-scale Extraction --- p.47 / Chapter 2.2 --- Physico-Chemical Characterization of HE-polysaccharides --- p.52 / Chapter 2.2.1 --- Carbohydrate Content: Phenol-Sulfuric Acid Method --- p.52 / Chapter 2.2.2 --- Protein Content: Lowry Assay --- p.52 / Chapter 2.2.3 --- Uronic Acid Content --- p.53 / Chapter 2.2.4 --- Molecular Weight Determination by High Pressure Liquid Chromatography (HPLC) --- p.55 / Chapter 2.2.5 --- Determination of Monosaccharide Composition of Non-Starch Polysaccharides by Gas Chromatography (GC) --- p.56 / Chapter 2.2.5.1 --- Acid Depolymerisation --- p.56 / Chapter 2.2.5.2 --- Neutral Sugar Derivatisation --- p.56 / Chapter 2.2.5.3 --- Determination of Neutral Sugar Composition by Gas Chromatography (GC) --- p.57 / Chapter 2.2.6 --- Structural Study of Polysaccharides by Methylation --- p.59 / Chapter 2.2.6.1 --- Preparation of dry Dimethyl Sulfoxide (DMSO) --- p.59 / Chapter 2.2.6.2 --- Preparation of Methylsulfinyl Methyl Sodium (CH3SOCH2-Na+) from the dry DMSO and Sodium Hydride --- p.59 / Chapter 2.2.6.3 --- Methylation Procedure --- p.60 / Chapter 2.2.6.4 --- Preparation of Partially Methylated Alditol Acetates (PMAAs) --- p.61 / Chapter 2.2.6.5 --- Analysis of the PMAAs by GC --- p.62 / Chapter 2.2.7 --- The Measurement of Viscosity --- p.62 / Chapter 2.3 --- In vitro Hypoglycemic Tests of HE-Polysaccharides --- p.64 / Chapter 2.3.1 --- Glucose Dialysis Retardation Index (GDRl) --- p.64 / Chapter 2.3.1.1 --- Experimental Setup --- p.64 / Chapter 2.3.1.2 --- Measurement of Glucose in the Dialysate --- p.65 / Chapter 2.3.2 --- Inhibition of Amylolysis --- p.66 / Chapter 2.3.2.1 --- Experimental Setup --- p.66 / Chapter 2.3.2.2 --- Measurement of Maltose in the Dialysate --- p.66 / Chapter 2.4 --- In vivo Hypoglycemic Evaluation of HE-Polysaccharides --- p.67 / Chapter 2.4.1 --- Oral Glucose Tolerance Test (OGTT) --- p.67 / Chapter 2.4.2 --- Induction of Type l Diabetes in Normal BALB/c Mice --- p.69 / Chapter 2.4.2.1 --- lnduction Protocol --- p.69 / Chapter 2.4.2.2 --- Measurement of Plasma Glucose Level --- p.70 / Chapter 2.4.3 --- Hypoglycemic Test on Normal and Diabetic BALB/c Mice --- p.71 / Chapter 2.4.4 --- Measurement of Insulin Level by Enzyme-Linked Immunoadsorbent Assay (ELlSA) --- p.72 / Chapter 2.4.4.1 --- Plasma Samples used in ELlSA --- p.72 / Chapter 2.4.4.2 --- Assay Procedure --- p.73 / Chapter 2.5 --- Statistical Evaluation --- p.74 / Chapter Chapter 3 --- Results and Discussion --- p.75 / Chapter 3.1 --- Yield of Polysaccharides extracted from H. erinaceus --- p.75 / Chapter 3.2 --- Physico-chemical Properties of HE Polysaccharides --- p.79 / Chapter 3.2.1 --- "Carbohydrate, Protein and Uronic Acid Content" --- p.79 / Chapter 3.2.2 --- Monosaccharide Compositions --- p.83 / Chapter 3.2.3 --- Molecular Weight of the HE polysaccharides --- p.85 / Chapter 3.2.4 --- Structure of HE polysaccharides --- p.90 / Chapter 3.2.5 --- Conclusion for the Physico-chemical Properties of HE-Polysaccharides --- p.96 / Chapter 3.2.6 --- Viscosity of HE Polysaccharides --- p.99 / Chapter 3.3 --- In vitro Study of the Hypoglycemic Effect of HE-Polysaccharides --- p.101 / Chapter 3.3.1 --- Glucose Dialysis Retardation Index (GDRl) --- p.101 / Chapter 3.3.2 --- Inhibition of α-Amylase Activity --- p.105 / Chapter 3.4 --- In vivo Hypoglycemic Evaluation of HE-Polysaccharides --- p.109 / Chapter 3.4.1 --- In vivo Oral Glucose Tolerance Test (OGTT) in Normal Mice --- p.109 / Chapter 3.4.1.1 --- Oral Glucose Tolerance Test --- p.109 / Chapter 3.4.1.2 --- Effect of Change of Viscosity of HE Polysaccharide in the Gl Tract of Mice --- p.114 / Chapter 3.4.2 --- Establishment of a Diabetic Murine Model --- p.120 / Chapter 3.4.3 --- Hypoglycemic Activity of HE-polysaccharides in Normal Mice --- p.123 / Chapter 3.4.4 --- Hypoglycemic Activity of HE-polysaccharides in Diabetic Mice --- p.126 / Chapter 3.4.5 --- Change of Plasma Insulin Level in the Hypoglycemic Test --- p.132 / Chapter 3.4.6 --- Comparison of Hypoglycemic Activity of HE-Polysaccharides in Normal and Diabetic mice --- p.139 / Chapter 3.4.6.1 --- Severity of Diabetic Conditions lnduced --- p.139 / Chapter 3.4.6.2 --- Change in Insulin Secretion --- p.140 / Chapter 3.4.6.3 --- Glucose Transporter --- p.140 / Chapter 3.5 --- Other Factors that Affect in vivo Hypoglycemic Activity of the HE-polysaccharides --- p.141 / Chapter 3.5.1 --- Route of Administration: Oral Feeding and Intraperitoneal Injection --- p.141 / Chapter 3.5.2 --- Molecular Mechanisms of Hypoglycemic Activity --- p.142 / Chapter 3.5.3 --- Glucose Toxicity --- p.144 / Chapter 3.5.3.1 --- Insulin Resistance --- p.144 / Chapter 3.5.3.2 --- Impaired Insulin Secretion --- p.145 / Chapter Chapter 4 --- Conclusions and Future Works --- p.147 / References --- p.151

Submitted in fulfillment of the requirements of the degree of Master in Technology, Department of Biomedical Technology and Clinical Technology, Durban University of Technology, Durban, South Africa, 2016. / Introduction In Africa, use of phytotherapy for treatment of diabetes mellitus is a common form of practice. Considering the increasing burden of non-communicable diseases in South Africa efforts are directed at simple, cost effective, non-hazardous and efficient methods to treat cancer, cardiovascular diseases and diabetes. The role of phytonanotherapy is an attractive proposition for advancing new therapies. Metal nanoparticles are a possible means for delivery of such therapies. However, this requires investigation on interactions, mechanisms and therapeutic efficacy upon co-administering ethnobotanicals with metal nanoparticles and existing drug therapy in human beings. Aim The primary aim of the study was to test the in vitro antidiabetic and antibacterial activity of Ocimum sanctum (leaf extracts and flower extracts), Ocimum basilicum (leaf extracts and flower extracts), and a combination of the leaf extracts of both, and to observe whether any antidiabetic and antibacterial activity was enhanced in due to phyto-synthesised bimetallic gold-silver (Au-Ag) nanoparticles and silver nanoparticles. Methods Aqueous and ethanol extracts of O. sanctum and O. basilicum leaf and flowers alone and combined (leaf + flower) were prepared using hot vs cold water extraction techniques and 60% and 70% ethanol as polar solvents. A simple, rapid, cost effective and reproducible green chemistry method synthesised alloyed bimetallic (Au-Ag) nanoparticles using O. basilicum leaf and flower aqueous extracts and prepared silver nanoparticles (AgNps) using O. basilicum and O. sanctum leaf aqueous extracts singly and in combination (O. sanctum + O. basilicum). The size, shape and elemental analysis of the nanoparticles was carried out using UV-Visible spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy coupled with energy-dispersive X-ray (SEM-EDX), dynamic light scattering (DLS) and zeta potential. Fourier transform infrared spectroscopy (FT-IR) supported by gas chromatography mass spectroscopy (GC-MS) identified the bio-capping agents. Antidiabetic carbohydrate metabolising enzymes, α-amylase (porcine) and Bacillus stearothermophilus α-glucosidase as models tested the in vitro inhibitory potential of the aqueous and ethanol plant extracts and the phyto-synthesised (Au-Ag) bimetallic and AgNps. In addition, the study investigated the antibacterial potential for the aqueous plant preparations and their respective phyto-synthesised bimetallic and AgNps against the bacterial species Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella species and Pseudomonas aeruginosa compared to gentamycin and vancomycin. Results Bimetallic nanoparticles (synthesised from leaf and flower aqueous extracts) displayed inhibitory activity that showed uncompetitive inhibition (leaf extract), and non-competitive inhibition (flower extract) of α-amylase and competitive (leaf extract) and uncompetitive inhibition (flower extract) of α-glucosidase. Bimetallic nanoparticles were higher in inhibitory activity than acarbose and the crude O. basilicum ethanol and aqueous leaf and flower extracts. In the antibacterial analysis, bimetallic nanoparticles derived from O. basilicum leaf showed inhibition against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa and were greater in activity compared to the crude aqueous leaf extract from O. basilicum. The in vitro inhibitory effect of AgNps derived from O. sanctum and AgNps derived from O. basilicum on both enzymes was higher in activity than acarbose and their respective crude extracts. However, in combination (O. sanctum + O. basilicum), the derived AgNps appeared to be a less potent inhibitor of α-amylase and α-glucosidase enzyme and was lower than acarbose. AgNps synthesised from the combination of O. sanctum and O. basilicum showed the highest percentage inhibition against Bacillus stearothermophilus α-glucosidase, and AgNps derived from O. sanctum and AgNps derived from O. basilicum displayed competitive type of inhibition. In the antibacterial analysis, AgNps derived from the various extracts showed zones of inhibition against the Gram negative and Gram positive bacterial test strains. However, AgNps synthesised from the O. sanctum leaf extract showed higher inhibition against Escherichia coli than the positive control gentamycin and higher inhibition against Staphylococcus aureus compared to vancomycin. In addition, AgNps from O. sanctum leaf extract displayed inhibition against Bacillus subtilis, Pseudomonas aeruginosa and Salmonella species, thus representing the highest antibacterial potential. Conclusion The results demonstrate the possibility of synthesis of stable silver and bimetallic nanoparticles of Ocimum sp. The synthesised silver nanoparticles and first time synthesis of bimetallic (Au-Ag) nanoparticles displayed enhanced antihyperglycaemic properties compared to their respective crude extracts and, therefore, show promising effects in lowering postprandial hyperglycaemia in diabetic patients with dual potential for antibacterial treatment. However, the antidiabetic and antibacterial effect will need to be further affirmed in a clinical context. Medicinal plants with therapeutic value may create a new platform for further research to explore the potential for herbal medicine and nanoscience as effective biomedical and industrial applications, and for improving existing drug delivery systems in diabetic patients. Investigations into the cytotoxicity of these extracts and phytosynthesised nanoparticles is recommended. / M

Class of 2010 Abstract / OBJECTIVES: To evaluate glycemic control, therapy associated weight loss/gain, and hypoglycemic events for the newer type 2 diabetic agents pramlintide, exenatide, and sitagliptin. METHODS: The meta-analysis examined the efficacy of three currently FDA approved peptide analogues in nonpregnant adults with type 2 diabetes mellitus. All randomized, placebo controlled trials of exenatide, pramlintide, and sitagliptin that were indexed in MEDLINE or and the Cochrane Database of Systematic Reviews that fit the inclusion criteria were included. The drug treatment efficacy was analyzed in terms of HbA1c (glycosylated hemoglobin) change from baseline compared to placebo in trials lasting at least 12 weeks. Weight change from baseline per treatment group was also a primary measure. The safety of the treatments was assessed in terms of number of hypoglycemic events noted in the clinical trials. Each of these dependent variables was assessed separately for the three products. RESULTS: The meta-analysis of the six exenatide articles included in the analysis found statistically significant reductions in both HbA1c and weight when compared to placebo. However, patients were three times as likely to experience hypoglycemia with exenatide than placebo (RR= 3.01 95%CI[0.427 to 3.865]). Meta-analysis of pramlintide studies showed statistically significant lowering of HbA1c and weight. Overall pramlintide resulted in a rate of hypoglycemia nearly equal to that of placebo (RR= 0.94 95%CI[0.699 to 1.265]). Meta-analysis of sitagliptin found statistically significant reductions in HbA1c compared to placebo. However, sitagliptin use was not associated with a reduction in weight in the random effects meta-analysis model. In terms of hypoglycemic events, sitagliptin use was associated with 2.89 times greater risk of causing hypoglycemic episodes compared to placebo (RR=2.89 95%CI[0.704 to 5.877]). CONCLUSIONS: All three newer products were associated with improved glycemic control compared to placebo. Improvement in weight was associated with exenatide and pramlintide treatment. Pramlintide was not associated with an increase in hypoglycemic episodes.