alpha-Glucosidase from yeast was used to screen for alpha-glucosidase inhibitory activities in Chinese herbal medicines. Seventy crude extracts were studied. The extracts of Semen Fagopyri Esculenti, Herba Euphorbiae Humifusae, Radix Polygoni Multiflori, Cortex Cinnamomi, Radix Paeoniae Rubra, and Radix Paeoniae Alba exhibited alpha-glucosidase inhibitory activities. These herbs have high potential for finding active compounds to develop into new antidiabetic drugs. / In this study, an assay technique involving brush border membrane vesicles was developed to screen for glucose uptake inhibitory actions in sixteen compounds from natural sources. Two compounds, namely naringenin and desoxyrhaponticin, were demonstrated to exhibit moderate inhibitory action on glucose uptake in rabbit intestinal brush border membrane vesicles, and showed very strong inhibitory action in rat everted intestinal sleeves. The kinetics study indicated that they behave as competitive inhibitors on glucose uptake. Moreover, they could reduce the level of the glucose uptake in the diabetic rat intestinal and renal membrane vesicles. In vivo study further demonstrated that desoxyrhaponticin could significantly reduce the glucose levels after a single oral administration of glucose in neonatal streptozotocin-induced diabetic rats, but not naringenin. These results suggest that naringenin and desoxyrhaponticin may be useful in the control of hyperglycemia. They act by inhibiting glucose uptake in the intestine and glucose reabsorption in the renal proximal tubules. / On the other hand, several synthetic compounds based on the structure of valienamine were found to show strong inhibition on intestinal alpha-glucosidases such as sucrase, glucoamylase and maltase. The strongest inhibitor was further studied. It could reduce the postprandial plasma glucose level of neonatal streptozotocin-induced diabetic rats. These results demonstrated that it has the potential to develop inter an oral antihyperglycemic agent. / The objective of this study is to improve the postprandial hyperglycemic conditions of diabetes by two approaches: (1) inhibiting the digestive enzymes (alpha-glucosidases), and (2) inhibiting active glucose transport in the small intestine. We have screened for new inhibitors of alpha-glucosidase and monosaccharide cotransporters from natural products and their derivatives. These compounds may be useful in the management of type 2 diabetes and diabetic complications. / Type 2 diabetes mellitus accounts for 90-95% of all diabetic cases and has become a major health concern over the world. There is increasing evidence that postprandial hyperglycemia, a hallmark of diabetes, plays a critical role in the development of type 2 diabetes and cardiovascular complications. Therefore the early identification of postprandial hyperglycemia and its effective control can offer the potential for early intervention and prevention of diabetic complications. / Li Jianmei. / "August 2006." / Adviser: Christopher H. K. Cheng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1592. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 161-180). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Fan, Rongrong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 130-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Additionally, cyclosporin A, an inhibitor of the mitochondrial permeability transition (MPT) pore, failed to prevent hIAPP-induced DeltaPsim collapse, cytochrome c and AIF release and caspase-3 activation, indicating that the MPT pore was not involved in hIAPP-induced apoptosis. On the other hand, potential crosstalk between the extrinsic and intrinsic apoptotic pathways was demonstrated by cleavage of Bid by caspase-8 in the apoptotic process triggered by hIAPP. / It is widely accepted that human islet amyloid polypeptide (hIAPP) aggregation plays an important role in the loss of insulin-producing pancreatic beta cells. Insulin secretion impairment and cell apoptosis can be due to mitochondrial dysfunction in pancreatic beta cells. hIAPP-induced cytotoxicity is mediated by the generation of reactive oxygen species (ROS). Phycocyanin (PC) is a natural compound from blue-green algae that is widely used as food supplement. Currently, little information is available about the effect of hIAPP on mitochondrial function of beta cells and protection of PC against hIAPP-induced cytotoxicity. In this thesis, I hypothesize that hIAPP may impair beta cell function with the involvement of mitochrondrial dysfunction, and this effects could be attenuated by PC. Therefore, the aim of this study was to investigate the role of mitochondria in hIAPP-induced apoptosis, the in vitro protective effects of PC and explore the underlying mechanisms. / It was found that hIAPP induced apoptosis in INS-1E cells with the disruption of mitochondrial function, as evidenced by ATP depletion, mitochondrial mass reduction, mitochondrial fragmentation and loss of mitochondrial membrane potential (DeltaPsim). Further molecular analysis showed that hIAPP induced changes in the expression of Bcl-2 family members, release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria into cytosol, activation of caspases and cleavage of poly (ADP-ribose) polymerase. Interestingly, the hIAPP-induced mitochondrial dysfunction in INS1-E cells was effectively restored by co-treatment with PC. / Our results showed that hIAPP inhibited the INS-1E cell growth in a dose-dependent manner. However, cytotoxicity of hIAPP was significantly attenuated by co-incubation of the cells with PC. hIAPP induced DNA fragmentation and chromatin condensation, which were key characteristics of cell apoptosis. These changes were inhibited by PC as examined by TUNEL assay and DAPI staining. Moreover, PC significantly prevented the hIAPP-induced overproduction of intracellular ROS and malonaldehyde (MDA), as well as changes of activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Furthermore, hIAPP triggered the activation of mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinase (JNK) and p38 kinase, and these effects were effectively suppressed by PC. / Taken together, I have demonstrated for the first time the involvement of mitochondrial dysfunction in hIAPP-induced INS-1E cell apoptosis, which was attenuated by PC through attenuating oxidative stress, modulating JNK and p38 pathways and reducing mitochondrial dysfunction. / Li, Xiaoling. / Adviser: Juliana Chung Ngor Chan. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 150-159). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Chan Siu-Wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 173-200). / Abstracts in English and Chinese; appendix in Chinese. / Table of Contents --- p.i / Abstract --- p.v / 論文摘要 --- p.ix / Acknowledgments --- p.xii / Table of Figures --- p.xiii / Table of Tables --- p.xvii / Chapter Chapter 1. --- Introduction --- p.1 / Chapter Chapter 2. --- Literature Review --- p.3 / Chapter 2.1 --- Diabetes Mellitus (DM)： Overview --- p.3 / Chapter 2.1.1 --- Diagnosis and Diagnostic Criteria --- p.4 / Chapter 2.1.2 --- Classifications of Diabetes Mellitus --- p.8 / Chapter 2.1.3 --- Management of Type 2 Diabetes Mellitus --- p.15 / Chapter 2.2 --- Diabetes Mellitus Complications： Overview --- p.25 / Chapter 2.2.1 --- Microvascular Complications --- p.26 / Chapter 2.2.2 --- Macrovascular Complications --- p.31 / Chapter 2.3 --- Type 2 Diabetes Mellitus - A Rising Global Burden --- p.32 / Chapter 2.3.1 --- Prevalence of Type 2 Diabetes Mellitus --- p.32 / Chapter 2.3.2 --- Prevalence of Type 2 Diabetes Mellitus in Hong Kong --- p.36 / Chapter 2.3.3 --- Mortality and Morbidity of Type 2 Diabetes Mellitus in Hong Kong --- p.40 / Chapter 2.4 --- cost of Type 2 Diabetes Mellitus - Under-explored Area in Hong Kong and Asia --- p.46 / Chapter 2.4.1 --- Cost of Type 2 Diabetes Mellitus in the USA --- p.48 / Chapter 2.4.2 --- Cost of Type 2 Diabetes Mellitus in Europe --- p.57 / Chapter 2.4.3 --- Cost of Type 2 Diabetes Mellitus in Asia-Pacific --- p.61 / Chapter 2.5 --- Hong Kong Healthcare System --- p.65 / Chapter 2.5.1 --- Hospital Authority in Hong Kong (Public Healthcare Sector) --- p.67 / Chapter 2.5.2 --- Hong Kong Healthcare Financing System --- p.73 / Chapter 2.6 --- New Emerging Drug Treatment for Type 2 DM in Hong Kong Chinese - Rosiglitazone --- p.77 / Chapter 2.6.1 --- Clinical Efficacy and Tolerability of Rosiglitazone --- p.77 / Chapter 2.6.2 --- Cost-effectiveness of Rosiglitazone --- p.78 / Chapter Chapter 3. --- Hypothesis and Objectives --- p.81 / Chapter 3.1 --- Cost of Type 2 Diabetes Mellitus in Hong Kong Chinese --- p.81 / Chapter 3.1.1 --- Hypothesis --- p.81 / Chapter 3.1.2 --- Objectives --- p.81 / Chapter 3.2 --- Cost-effectiveness Analysis of Metformin + Rosiglitazone vs. Metformin + Glibenclamide for Type 2 DM Patient Whose Diabetes is not Adequately Controlled by Metformin Alone from a Payer's Perspective --- p.82 / Chapter 3.2.1 --- Hypothesis --- p.82 / Chapter 3.2.2 --- Objectives --- p.83 / Chapter Chapter 4. --- Cost of Type 2 Diabetes Mellitus in Hong Kong Chinese --- p.84 / Chapter 4.1 --- Subjects and Methods --- p.84 / Chapter 4.1.1 --- Subjects --- p.84 / Chapter 4.1.2 --- Methods --- p.85 / Chapter 4.1.3 --- Validity and Reliability of the Chinese Questionnaire --- p.96 / Chapter 4.2 --- Results --- p.96 / Chapter 4.2.1 --- Subjects' Characteristics --- p.96 / Chapter 4.2.3 --- Comorbidity --- p.102 / Chapter 4.2.4 --- Complications --- p.102 / Chapter 4.2.5 --- Costs of Type 2 DM --- p.104 / Chapter 4.3 --- Discussions --- p.123 / Chapter Chapter 5 --- Cost-effectiveness Analysis of Metformin + Rosiglitazone vs. Metformin + Glibenclamide for Type 2 DM Patient Whose Diabetes is not Adequately Controlled by Metformin Alone from a Payer's Perspective --- p.134 / Chapter 5.1 --- Methods --- p.134 / Chapter 5.1.1 --- Model Overview --- p.134 / Chapter 5.1.2 --- "Success, Failure and Discontinuation Rates" --- p.138 / Chapter 5.1.3 --- Resources Use and Costs --- p.142 / Chapter 5.1.4 --- Health-Related Quality of Life (HRQOL) --- p.148 / Chapter 5.1.5 --- Base Case Analysis --- p.149 / Chapter 5.1.6 --- Sensitivity Analyses --- p.149 / Chapter 5.2 --- Results --- p.150 / Chapter 5.2.1 --- Base Case Model - CE Analysis: cost per controlled Type 2 DM patient --- p.150 / Chapter 5.2.2 --- Sensitivity Analysis- CE Analysis: cost per controlled Type 2 DM patient --- p.151 / Chapter 5.2.3 --- Base Case Model - CE Analysis: cost per EQ5D utility score --- p.154 / Chapter 5.2.4 --- Sensitivity Analysis- CE Analysis: cost per EQ5D utility score --- p.155 / Chapter 5.3 --- Discussions --- p.158 / Chapter Chapter 6. --- Conclusions --- p.163 / Appendix --- p.165 / References