在2型糖尿病病人身上，常常併發高膽固醇血症，HMG CoA 還原酶的抑制劑常常用作治療這類病症。由於高膽固醇血症與胰島素抵抗和2型糖尿病有著密切關係，我們推測辛伐他汀對於2型糖尿病的發展有著保護和有利的作用。在這項研究中，我們主要測試了辛伐他汀 （10 nM； 24 hr）對於胰島β細胞主要功能的影響，包括其對於葡萄糖的胰島素分泌功能影響。我們假設，在肥胖/糖尿病（db⁺/ db⁺）小鼠分離的胰島，辛伐他汀可以恢復葡萄糖 （5 mM和15 mM）引起的胰島素分泌（加上降低的胰島素含量）。 / 在這個項目中，我們運用24周大的基因糖尿糖C57BL/KSJ +db/+db (db⁺/db⁺)肥鼠和相同年齡的無糖尿病C57BL/KSJ +m/+m (db⁺/m⁺)小鼠作為動物模型。通過應用obese/diabetic (db+/db+)和lean/non-diabetic (db+/m+)中分離的胰腺胰島和胰島β細胞，我們研究了胰腺胰島功能性障礙的潛在機理以及辛伐他汀對於恢復葡萄糖 （5 mM和15 mM）引起的胰島素分泌（加上降低的胰島素含量）的有利作用。資料清晰的顯示，葡萄糖引起的胰島素分泌和胰島素含量在obese/diabetic (db+/db+)的胰腺胰島中明顯低於在lean/non-diabetic (db⁺/m⁺)的胰腺胰島中。在24hr的辛伐他汀處理後，辛伐他汀恢復了葡萄糖 （5 mM和15 mM）引起的胰島素分泌（加上降低的胰島素含量）及葡萄糖 （15 mM）引起的胞內鈣離子變化。 / 在這個項目中，我們證明鈣敏感受體 （CaSR）在obese/diabetic (db⁺/db⁺)中的表達量明顯較低，而辛伐他汀的處理可以顯著性增加鈣敏感受體在obese/diabetic (db⁺/db⁺)胰島中的表達。有人建議說，obese/diabetic (db⁺/db⁺)的胰島中被抑制的鈣敏感受體表達與胰島β細胞的胰島分泌功能障礙有關。這暗示了辛伐他汀可能通過變構啟動鈣敏感受體來恢復obese/diabetic (db⁺/db⁺)胰島中葡萄糖引起的胰島素分泌和胰島含量。實驗也同樣証明辛伐他汀調節的PLA₂信號通路對於辛伐他汀改善obese/diabetic (db⁺/db⁺)胰島β細胞的胰島素分泌功能起著至關重要的作用。除此之外，我們的實驗結果證明高濃度的葡萄糖處理顯著的增加了obese/diabetic (db⁺/db⁺)細胞膜肌動蛋白骨架的密度，而辛伐他汀顯著的減少了這一變化。因此，obese/diabetic (db⁺/db⁺)胰島β細胞的胰島素分泌障礙是由肌動蛋白細胞骨架聚集阻礙胰島素顆粒胞吐引起的。而辛伐他汀通過解聚和重組肌動蛋白細胞骨架來改善obese/diabetic (db⁺/db⁺)胰島β細胞的胰島素分泌功能。 / 在這項研究中，我們的實驗結果證明葡萄糖可以顯著提高obese/diabetic (db⁺/db⁺)胰島β細胞內ROS的含量。而辛伐他汀處理部分降低了胰島β細胞內ROS的含量。除此之外，我們還研究了5 mM和15 mM葡萄糖對於內質網應力（ER-stress）相關的蛋白比如PERK, eIF2α 和IRE1表達的影響。這些內質網跨膜蛋白可以感應ER-stress從而啟動應力感測器來開啟複雜的信號通路。與lean/non-diabetic (db⁺/m⁺)相比，PERK and eIF2α在obese/diabetic (db⁺/db⁺)的胰島中表達量更低，這表明obese/diabetic (db⁺/db⁺)胰島β細胞的功能性障礙可能與ER-stress有關。而辛伐他汀的處理明顯的增加了這些蛋白的表達量，由此證明辛伐他汀還通過對抗ER-stress來保護obese/diabetic (db⁺/db⁺)胰島β細胞。 / 總而言之，我們的資料第一次證明了辛伐他汀通過PLA₂信號通路變構啟動鈣敏感受體來保護obese/diabetic (db⁺/db⁺)胰島β細胞（比如：恢復葡萄糖引發的胰島素分泌和提高減少的胰島素含量），還通過提高obese/diabetic (db⁺/db⁺)胰島β細胞中被抑制的ER-stress相關蛋白的表達量來抵抗ER-stress帶來的損傷。 / Diabetics often have hyperlipidemia as a co-morbidity. Despite the well-documented cholesterol-lowering properties of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) in treating hypercholesterolemia, the beneficial effects of statins consumption in T2DM treatment are confusing. In the current study, we examined the effects of the simvastatin (10 nM; 24 hr) on β-cell function leading to insulin secretory response to glucose. We hypothesized that statins restore the blunted glucose (5 mM and 15 mM)-induced insulin secretion (plus the reduced insulin content) of isolated pancreatic islets of obese/diabetic (db⁺/db⁺) mice. / In the present study, genetically diabetic C57BL/KSJ +db/+db (db⁺/db⁺) mice at 24 week of age and their age-matched non-diabetic littermates C57BL/KSJ +m/+m (db⁺/m⁺) were used. Our results clearly showed that the suppressed glucose (5 mM and 15 mM)-induced insulin release (plus insulin content) and glucose (15 mM)-induced [Ca²⁺]i changes of isolated pancreatic islets of obese/diabetic (db⁺/db⁺) was restored after simvastatin (10 nM; 24 hr) treatment. / The biochemical existence of CaR in pancreatic islets of lean/non-diabetic (db⁺/m⁺) and obese/diabetic (db⁺/db⁺) mice was confirmed. The suppressed/down-regulated expression of CaR was associated to the blunted insulin secretion in pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice, and it was markedly up-regulated by simvastatin (10 nM; 24 hr). The involvement of CaR-mediated PLA₂ signaling in simvastatin (10 nM; 24 hr)-induced restoration of glucose (15 mM)-induced insulin secretion in pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice was investigated. Our results also showed that the increased density of plasma membrane actin cytoskeleton of obese/diabetic (db⁺/db⁺) mice was significantly decreased by simvastatin (10 nM; 24 hr) treatment. The simvastatin-induced depolymerization and remodeling of actin cytoskeleton may improve insulin secretion capability in pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice. / The glucose (15 mM)-induced intracellular ROS level was significantly higher in pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice. The elevated ROS level was partially diminished by simvastatin (10 nM; 24 hr) treatment. The protein expressions of PERK and eIF2α (ER stress proteins) were lower in pancreatic islet cells isolated from obese/diabetic (db⁺/db⁺) mice, suggesting that abnormal expresstion/activity of PERK and eIF2α would be coupled to the ER-stress mediated failure of pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice. As simvastatin (10 nM; 24 hr) up-regulated the protein expression of these proteins, this drug exerted protective effect on pancreatic β-cells against ER stress and restored the blunted glucose (15 mM)-induced insulin secretion (plus the reduced insulin content) in obese/diabetic (db⁺/db⁺) mice. / In conclusion, our results demonstrate, for the first time, that simvasatatin (a HMG-CoA reductase inhibitor) (10 nM; 24 hr) provides beneficial effects (i.e. restoration of the blunted glucose-induced insulin release plus the reduced insulin content) in pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice via the allosteric modification/up-regulation of extracellular calcium-sensing receptor through the PLA₂ signaling pathway, and provides protective/antioxidant effects against oxidative stress caused by chronic hyperglycemia in pancreatic β-cells of obese/diabetic (db⁺/db⁺) mice by up-regulating protein expression of the suppressed ER stress sensors and antioxidant enzyme. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Au, Lai Shan. / Thesis (Ph.D.) Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 458-532). / Abstracts also in Chinese.

Objetivos: Avaliar o impacto da terapia periodontal supragengival nos parâmetros clínicos e microbiológicos de pacientes portadores de Diabetes Mellitus tipo 2 (DMT2) em um período de 6 meses, através da utilização do PCR (reação em cadeia da polimerase) em tempo real. Material e Métodos: A amostra foi composta por 20 pacientes portadores de DMT2. Os indivíduos foram randomizados em dois grupos diferentes e receberam duas formas de tratamento periodontal. O grupo teste, composto por 10 indivíduos, recebeu terapia periodontal supragengival (TPS) e o grupo controle, também com 10 indivíduos, recebeu terapia periodontal intensiva (TPI), considerada como o padrão ouro. Ambos os grupos receberam orientação de higiene (OHB), durante os 6 meses da realização do estudo. Foram coletadas amostras de biofilme subgengival em um sítio raso e outro profundo, antes do tratamento periodontal e após seis meses do seu término, perfazendo um total de 4 amostras por paciente. Foram avaliadas quatro bactérias periodontais (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia e Treponema denticola) e também foi feita a contagem Universal das bactérias presentes. O estudo avaliou um total de 80 amostras. Foram também coletados os dados clínicos periodontais. A quantidade de bactérias pré e pós tratamento foi determinada pela técnica de PCR em tempo real. Os dados clínicos e microbiológicos foram analisados por métodos estatísticos não-paramétricos. Resultados: A análise dos dados demográficos e clínicos no baseline, mostrou não haver diferenças entre os grupos TPS e TPI. Existem diferenças significativas entre os tratamentos com relação à melhora do sangramento (p<0,001) e profundidade clínica de sondagem (PCS) (p=0,011), em ambos à melhora pelo tratamento TPI é maior. Quanto a melhora dos parâmetros clínicos periodontais em cada um dos grupos após 6 meses, apenas a supuração não melhorou para o grupo TPS. Os demais parâmetros clínicos melhoram significativamente em ambos os tratamentos. Com relação aos dados microbiológicos, nas bolsas rasas os grupos são diferentes para a medida de A. actinomycetemcomitans e P. gingivalis na avaliação de 6 meses. No entanto, quando comparamos as diferenças (log final- log inicial), não houve diminuição significativa entre os grupos para nenhuma das bactérias. Com relação à diminuição do número de bactérias em cada um dos tratamentos, houve uma diminuição significativa para T. forsythia no grupo TPI. Nas bolsas profundas, quando comparamos as diferenças (log final- log inicial), não houve diminuição significativa entre os grupos para nenhuma das bactérias avaliadas, bem como após 6 meses em cada um dos tratamentos. Quando fazemos a razão do número de cópias de cada bactéria com relação ao número de cópias total (Universal) nas bolsas rasas, existe diferença significativa entre os grupos para P. gingivalis (p= 0,043) e A. actinomycetemcomitans (p= 0,019) na avaliação de 6 meses. Com relação à diminuição das proporções para cada um dos tratamentos após 6 meses, TPI foi capaz de reduzir significativamente o número de T. forsythia nas bolsas rasas (p=0,004) e o número de P. gingivalis nas bolsas profundas (p=0,037). / Objectives: To evaluate the supragingival periodontal therapy in clinical and microbiological parameters in subjects with type 2 diabetes mellitus (T2DM) in a 6 month period by using real-time PCR. Material and Methods: The study included 20 individuals with T2DM. The subjects were divided into two groups and received two different forms of periodontal treatment. A group of 10 individuals received supragingival periodontal treatment (SPT) and another, also with 10 patients received intensive periodontal treatment (IPT), the gold standard. Samples were collected from subgingival biofilm in shallow sites and deep sites before and after six months of the periodontal treatment, a total of four samples per patient. We evaluated four periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) and was also made Universal count of bacteria present. The study evaluated a total of 80 samples. Clinical parameters were also acessed. The amount of bacteria before and after treatment was determined by real time PCR. Clinical and microbiological data were analyzed by non-parametric statistical methods. Results: The analysis of demographic and clinical data at baseline, showed no differences between groups SPT and IPT. There are significant differences between the treatments with regard to improvement of bleeding (p<0.001) and probing depth (PD) (p=0.011) in both the IPT improvement is greater. Regarding the improvement of clinical periodontal parameters after 6 months for each group, only the suppuration has not improved for the SPT group. The other clinical parameters improved significantly in both treatments. Regarding the microbiological data in the shallow sites, the groups are different for the measurement of A. actinomycetemcomitans and P. gingivalis in the evaluation of 6 months. However, when comparing the differences (end log inicial log), there was no significant decrease between groups for any of the bacteria. With respect to reducing the number of bacteria in each of the treatments, there was a significant decrease in T. forsythia for IPT. In the deep sites, the groups are different for the measurement of A. actinomycetemcomitans at baseline. However, when comparing the differences (end log inicial log), there was no significant decrease between groups for any of the bacteria evaluated. There was also no significant decrease in the number of bacteria after 6 months in each treatment. When we make the ratio of the number of copies of each bacteria with respect to the number of complete copies (Universal) in shallow sites, there is a significant difference between groups for P. gingivalis (p=0.043) and A. actinomycetemcomitans (p = 0.019) in the evaluation of 6 months. With regard to reduction for each treatment after 6 months, IPT was able to significantly reduce the number of T. forsythia in shallow sites (p = 0.004) and the number of P. gingivalis in deep sites (p= 0.037).

Diabetes mellitus är en växande folksjukdom. Risken att drabbas av diabetes mellitus typ II ökar med åldern därför benämns den även vuxen eller åldersdiabetes. Blodsockerreglering som normalt är en automatisk och osynlig funktion i kroppen, kräver vid diabetes mellitus en medveten handling. För de flesta patienter innebär diabetes mellitus stora livsstilförändringar som till exempel att ha regelbundna tider för matintag, motionera, sluta röka, begränsa gamla vanor och eventuellt medicinering. Ansvaret av behandling ligger ytterst hos patienten själv. Att ha en kronisk sjukdom som diabetes mellitus kan många gånger innebära svårigheter som anpassning till de ändrade livssituationerna. Syftet med studien är att beskriva patientens upplevelser med att leva med sjukdomen. Metoden som valdes var en systematisk litteraturstudie. Modellen har valts för att den vetenskapliga kunskapen inom vårdverksamheten skall kunna bidra till grund för det praktiska vårdarbetet. Efter analys av tolv stycken vetenskapliga artiklar, fyra teman skapades. Teman visade patientens upplevelse i samband med den psykiska och fysiska hälsan, innehav av eget behandlingsansvar, samt utbildning och rådgivning som patienten får från vårdpersonalen. Studien visar, vilket framkommer i alla teman, att diabetespatienternas känslomässiga behov av att bemästra sin oro i samband med sjukdomen bör beaktas. Relationen mellan vårdaren och patienten bör läggas på en ömsesidig grund där det finns respekt och tilltro. / Program: Fristående kurs

No description available.

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.

O objetivo do presente trabalho foi investigar o efeito da hiperglicemia na alteração da homeostase imunológica mediada pelas células dendríticas (DCs) em resposta a uma bacteremia induzida por raspagem e alisamento radicular (RAR) em indivíduos com periodontite crônica generalizada (GCP). Foram selecionados 60 indivíduos igualmente divididos em quatro grupos: controles normoglicêmicos saudáveis, normoglicêmicos com GCP (NG+GCP), pré-diabéticos com GCP (PD+GCP) e diabéticos tipo 2 com GCP (T2DM+GCP). Os indivíduos com GCP receberam RAR, o que induziu uma bacteremia aguda e os controles saudáveis receberam apenas raspagem supragengival. Todos os participantes foram avaliados no início do estudo, 24hs, 1 mês e 3 meses após a raspagem. A frequência de células dendríticas mielóides (mDCs) CD1c+, mDCs CD141+, células dendríticas plasmocitoides (pDCs) CD303+ e a expressão dos receptores CCR6 (presente em altos níveis em células dendríticas imaturas) e CCR7 (presente em altos níveis em células dendríticas maduras) foram avaliados por citometria de fluxo. Foi utilizada técnica de PCR em tempo real para investigar a presença de Porphyromonas gingivalis (P. gingivalis) no biofilme e abrigada pelas DCs. No início do estudo, os indivíduos hiperglicêmicos com GCP tinham níveis de DCs significativamente mais baixos do que os indivíduos normoglicêmicos com ou sem GCP. Após a bacteremia induzida por RAR, observou-se um aumento significativo nos níveis de CD1c+ e CD1c+CCR6+ em todos os grupos com GCP, independentemente do status de glicemia, e esses níveis voltaram aos níveis basais após 1 mês. Em comparação com o grupo NG+GCP, o grupo T2DM+GCP apresentou níveis significativamente mais baixos de DCs ao longo de todos os períodos experimentais. Não foram observadas alterações significativas para CD303+, CD1c+ CCR7+ e CD141+ em resposta à bacteremia; CD303+ e CD141+ foram significativamente mais baixos para T2DM+GCP comparado ao grupo NG+GCP ao longo do estudo. A quantidade de P. gingivalis nas DCs estava aumentada no grupo NG+GCP no início do estudo e após 24h da RAR comparado ao controle, mas não nos grupos hiperglicêmicos. Os resultados premitiram concluir que a hiperglicemia parece afetar negativamente a presença de mDCs e pDCs no sangue periférico e a abilidade dessas células em capturar P. gingivalis. Considerando que a magnitude da expansão de mDCs em resposta a um desafio bacteriano foi semelhante, os indivíduos hiperglicêmicos permaneceram imunocomprometidos em comparação com indivíduos normoglicêmicos. / The objective of this study was to investigate the effect of hyperglycemia in the disruption of dendritic cells (DCs) mediated immune homeostasis in response to an acute short-term bacteremia in subjects with generalized chronic periodontitis (GCP). Sixty subjects equally divided into four groups were selected: normoglycemic healthy controls, normoglycemics with GCP (NG+GCP), pre-diabetics with GCP (PD+GCP), and type-2 diabetes mellitus with GCP (T2DM+GCP). Subjects with GCP received full-mouth scaling and root planning (SRP), which induced an acute bacteremia, while healthy controls received only a prophylaxis. All participants were examined at baseline, 24hs after SRP, 1 month, and 3 months. The frequency of CD1c+ myeloid DCs (mDCs), CD141+ mDCs, CD303+ plasmacytoid DCs (pDCs) and their expression of immature DC tissue homing receptor CCR6+ and secondary lymphoid organ (SLO)-homing receptor CCR7+ were analyzed by flow cytometry. The presence of Porphyromonas gingivalis (P. gingivalis) mRNA within blood DCs was analyzed by real time PCR. At baseline, hyperglycemic subjects with GCP showed lower DC levels than normoglycemic subjects with or without GCP. After SRP induced bacteremia, a significant increase in CD1c+ and CD1c+CCR6+ levels was observed in all GCP groups, which returned to baseline levels after 1 month. Compared to NG+GCP, T2DM+GCP had significantly lower levels of DCs throughout the experimental periods. No significant changes were observed for CD303+, CD1c+CCR7+ and CD141+ in response to the bacteremia; CD303+ and CD141+ were significantly lower for T2DM+GCP than NG+GCP throughout the study. P. gingivalis carriage state of DCs was increased in the NG+GCP group, but not in the hyperglycemic groups. Hyperglycemia appears to negatively affect the pool of mDCs and pDCs and the ability of blood DCs to captures bacteremic P. gingivalis. Whereas the magnitude of mDCs expansion in response to a bacterial challenge was similar, hyperglycemic subjects remained immunocompromised in comparison to normoglycemic subjects.

Ho Sin Ka Janice. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 105-119). / Abstracts in English and Chinese. / Chapter CHAPTER 1. --- Introduction / Chapter 1.1. --- Epidemiology of Type 2 Diabetes --- p.1 / Chapter 1.2. --- Risk factors contributing to Type 2 Diabetes --- p.3 / Chapter 1.2.1. --- Environmental and physiological factors --- p.3 / Chapter 1.2.2. --- Genetic factors --- p.3 / Chapter 1.3. --- Disruption of energy homeostasis in the pathogenesis of type 2 diabetes --- p.6 / Chapter 1.3.1. --- Clinical spectrum of diabetes --- p.6 / Chapter 1.3.2. --- Insulin as a key regulator of energy homeostasis --- p.7 / Chapter 1.3.3. --- Insulin secretion and glucose metabolism --- p.8 / Chapter 1.3.4. --- Insulin action and lipid metabolism --- p.9 / Chapter 1.3.5. --- Lipotoxicity and glucotoxicity --- p.12 / Chapter 1.3.6. --- Role of transcription factors as metabolic switch --- p.13 / Chapter 1.4. --- Candidate genes implicated in type 2 diabetes susceptibility --- p.15 / Chapter 1.4.1. --- Candidate genes involved in insulin secretion pathway --- p.15 / Chapter 1.4.1.1. --- HNF4A --- p.15 / Chapter 1.4.1.2. --- HNF1A --- p.16 / Chapter 1.4.1.3. --- PDX1/PBX1 --- p.17 / Chapter 1.4.1.4. --- NEUROD1 --- p.17 / Chapter 1.4.1.5. --- GCK --- p.17 / Chapter 1.4.1.6. --- KCNJ11/ABCC8 --- p.18 / Chapter 1.4.2 --- Candidate genes involved in insulin action pathway --- p.19 / Chapter 1.4.2.1. --- PPARG --- p.19 / Chapter 1.4.2.2. --- PPARA --- p.20 / Chapter 1.4.2.3. --- PPARGC1A --- p.20 / Chapter 1.4.2.4. --- ADIP0Q --- p.21 / Chapter 1.4.2.5. --- LPL --- p.21 / Chapter 1.4.2.6. --- UPC --- p.22 / Chapter 1.5. --- Hypothesis and objectives of the study --- p.23 / Chapter CHAPTER 2. --- Materials and methods / Chapter 2.1. --- Study design --- p.25 / Chapter 2.1.1. --- Two-stage candidate gene association design --- p.25 / Chapter 2.1.2. --- Power calculation --- p.27 / Chapter 2.2. --- Study cohort --- p.29 / Chapter 2.2.1. --- Subject recruitment --- p.29 / Chapter 2.2.2. --- Clinical and biochemical measurements --- p.30 / Chapter 2.2.3. --- Clinical definitions --- p.31 / Chapter 2.3. --- Genetic study --- p.32 / Chapter 2.3.1. --- Candidate gene selection --- p.32 / Chapter 2.3.2. --- SNP selection --- p.32 / Chapter 2.3.3. --- DNA sample preparation --- p.35 / Chapter 2.3.4. --- Genotyping methods --- p.36 / Chapter 2.3.4.1. --- Allele specific Tm shift assay --- p.36 / Chapter 2.3.4.2. --- Mass spectrometry assay --- p.40 / Chapter 2.4. --- Data quality control --- p.42 / Chapter 2.4.1. --- Stage 1 --- p.42 / Chapter 2.4.2. --- Stage 2 --- p.42 / Chapter 2.5. --- Statistical analysis --- p.45 / Chapter 2.5.1. --- Stage 1 analysis --- p.45 / Chapter 2.5.2. --- Stage 2 analysis --- p.45 / Chapter 2.5.3. --- Stage 1 and 2 combined analysis --- p.46 / Chapter CHAPTER 3. --- Results / Chapter 3.1. --- Clinical characteristics of subjects in stages 1 and 2 studies --- p.48 / Chapter 3.2. --- Case-control associations in stage 1 --- p.51 / Chapter 3.2.1. --- Association with T2D --- p.51 / Chapter 3.2.2. --- Association with T2D subset by metabolic syndrome --- p.54 / Chapter 3.3. --- Case-control associations in stage 2 --- p.60 / Chapter 3.3.1. --- SNP selection for genotyping --- p.60 / Chapter 3.3.2. --- Association with T2D --- p.63 / Chapter 3.3.3. --- Association with T2D subset by metabolic syndrome --- p.64 / Chapter 3.4. --- Case-control associations in combined stages 1 and 2 --- p.66 / Chapter 3.4.1. --- Association with T2D --- p.66 / Chapter 3.4.2. --- Association with T2D subset by metabolic syndrome --- p.70 / Chapter 3.4.3. --- Association with T2D subset by age at diagnosis --- p.74 / Chapter 3.4.4. --- Association with T2D subset by gender --- p.76 / Chapter 3.4.5. --- Genetic epistasis for T2D association --- p.79 / Chapter 3.5. --- Metabolic traits associations in control subjects in combined stages 1 and 2 studies --- p.83 / Chapter CHAPTER 4. --- Discussion --- p.86 / Chapter 4.1. --- Role of insulin secretion genes in type 2 diabetes --- p.87 / Chapter 4.2. --- Role of insulin action genes in type 2 diabetes --- p.92 / Chapter 4.3. --- Combined genetic effects on risk for type 2 diabetes --- p.97 / Chapter 4.4. --- Summary --- p.98 / Chapter 4.5. --- Limitation of this study and future direction --- p.101 / REFERENCES --- p.104 / APPENDICES --- p.119 / Chapter Appendix 1: --- Gene structure and linkage disequilibrium of genotyped SNPs of candidate genes --- p.119 / Chapter Appendix 2: --- Information of SNPs genotyped in stage 1 --- p.130 / Chapter Appendix 3: --- T2D association results (additive model) of 152 SNPs for stage 1 case- control samples --- p.137 / Chapter Appendix 4: --- T2D association results (additive model) of 152 SNPs for stage 1 case- control samples subset by metabolic syndrome status in cases --- p.144 / Chapter Appendix 5: --- T2D association results (additive model) of 22 SNPs for stage 2 case- control samples --- p.151 / Chapter Appendix 6: --- T2D association results (additive model) of 22 SNPs for stage 2 case- control samples subset by metabolic syndrome status in cases --- p.153

Lam Tsz Yan. / Thesis submitted in: October 2007. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references. / Abstracts in English and Chinese. / Abstract (English) --- p.i / 論文摘要 --- p.iv / Acknowledgements --- p.vi / Publications --- p.vii / Abbreviations --- p.ix / Contents --- p.x / Chapter 1. --- General Introduction --- p.1 / Chapter 1.1. --- Obesity --- p.1 / Chapter 1.1.1. --- Overview --- p.1 / Chapter 1.1.2. --- Pathophysiology --- p.1 / Chapter 1.1.3. --- Central obesity --- p.3 / Chapter 1.2. --- Diabetes --- p.7 / Chapter 1.2.1. --- Overview --- p.7 / Chapter 1.2.2. --- Pathophysiology --- p.8 / Chapter 1.3. --- Lipolysis --- p.9 / Chapter 1.3.1. --- Proteins participating in triglyceride lipolysis --- p.10 / Chapter 1.3.1.1. --- Hormone-sensitive lipase (HSL) --- p.10 / Chapter 1.3.1.2. --- Adipose triglyceride lipase (ATGL) --- p.10 / Chapter 1.3.1.3. --- Perilipins --- p.11 / Chapter 1.3.2. --- Abnormal regulation of lipolysis in obesity --- p.11 / Chapter 1.3.3. --- Disturbed lipolysis in insulin resistance --- p.13 / Chapter 1.4. --- Pharmacotherapy --- p.13 / Chapter 1.4.1. --- Obesity --- p.13 / Chapter 1.4.1.1. --- Orlistat --- p.13 / Chapter 1.4.1.2. --- Sibutramine --- p.14 / Chapter 1.4.1.3. --- Others --- p.15 / Chapter 1.4.2. --- Diabetes --- p.15 / Chapter 1.4.2.1. --- Modulation of the β-cells functions --- p.15 / Chapter 1.4.2.2. --- Control of glucose output --- p.16 / Chapter 1.4.2.3. --- Modulation of carbohydrate absorption --- p.16 / Chapter 1.4.2.4. --- Thiazolidinediones (TZDs) --- p.16 / Chapter 1.5. --- Animal models used in type 2 diabetes and obesity research --- p.17 / Chapter 1.6. --- Aim of study --- p.18 / Chapter 2. --- β-Adrenoceptors (β-ARs) --- p.21 / Chapter 2.1. --- Introduction --- p.21 / Chapter 2.1.1. --- Hormonal control of lipolysis --- p.21 / Chapter 2.1.1.1. --- Catecholamines --- p.21 / Chapter 2.1.1.2. --- Insulin --- p.23 / Chapter 2.1.2. --- Folic acid (folate) --- p.23 / Chapter 2.1.2.1. --- Physiological roles of folate --- p.23 / Chapter 2.1.2.2. --- Folate deficiency and its consequences --- p.24 / Chapter 2.1.2.3. --- Hyperhomocysteinemia --- p.24 / Chapter 2.1.2.4. --- Pleiotropic effects of folate --- p.25 / Chapter 2.1.2.5. --- Role of folate in type 2 diabetes and obesity --- p.26 / Chapter 2.1.3. --- Lingzhi --- p.28 / Chapter 2.1.3.1. --- Triterpenoids --- p.29 / Chapter 2.1.3.2. --- Polysaccharides --- p.30 / Chapter 2.2. --- Materials and methods --- p.32 / Chapter 2.2.1. --- Materials --- p.32 / Chapter 2.2.1.1. --- Composition of physiological salt solution --- p.32 / Chapter 2.2.1.2. --- Materials used in lipolysis experiment --- p.32 / Chapter 2.2.1.3. --- Materials used in reverse transcription polymerase chain reaction (RT-PCR) --- p.34 / Chapter 2.2.1.4. --- Materials used in Western blotting --- p.34 / Chapter 2.2.2. --- Methods --- p.36 / Chapter 2.2.2.1. --- Lipolysis experiment --- p.36 / Chapter 2.2.2.1.1. --- Animals --- p.36 / Chapter 2.2.2.1.2. --- Drug administration --- p.36 / Chapter 2.2.2.1.3. --- Isolation of adipocytes --- p.37 / Chapter 2.2.2.1.4. --- Lipolysis measurement --- p.37 / Chapter 2.2.2.1.5. --- Data analysis --- p.38 / Chapter 2.2.2.2. --- RT-PCR --- p.38 / Chapter 2.2.2.2.1. --- Tissue preparation --- p.39 / Chapter 2.2.2.2.2. --- RNA extraction --- p.39 / Chapter 2.2.2.2.3. --- Reverse transcription (RT) --- p.40 / Chapter 2.2.2.2.4. --- Polymerase chain reaction (PCR) --- p.40 / Chapter 2.2.2.2.5. --- Agarose gel electrophoresis --- p.41 / Chapter 2.2.2.2.6. --- Data representation and analysis --- p.41 / Chapter 2.2.2.3. --- Western blotting --- p.42 / Chapter 2.2.2.3.1. --- Tissue preparation --- p.42 / Chapter 2.2.2.3.2. --- Protein extraction --- p.42 / Chapter 2.2.2.3.3. --- Western blotting --- p.42 / Chapter 2.2.2.3.4. --- Data representation and analysis --- p.43 / Chapter 2.3. --- Results --- p.43 / Chapter 2.3.1. --- Studies on the β-adrenoceptor-mediated lipolytic response in +m/+db and +db/+db mice --- p.43 / Chapter 2.3.1.1. --- Effect of β2-adrenoceptor agonist on lipolysis --- p.43 / Chapter 2.3.1.2. --- Effect of β3-adrenoceptor agonists and their antagonists on lipolysis --- p.44 / Chapter 2.3.1.3. --- Effect of non-selective β-adrenoceptor agonists and their antagonists on lipolysis --- p.45 / Chapter 2.3.1.4. --- Effect of modulators of intracellular cyclic nucleotide monophosphate on lipolysis --- p.46 / Chapter 2.3.1.5. --- Effect of exogenously delivered nitric oxide on lipolysis --- p.47 / Chapter 2.3.1.6. --- Gene expression of β-adrenoceptors in white adipose tissue --- p.47 / Chapter 2.3.1.7. --- Protein expression of β-adrenoceptors in white adipose tissue --- p.47 / Chapter 2.3.2. --- Effect of folic acid treatment on lipolysis --- p.48 / Chapter 2.3.2.1. --- Determination of body weight --- p.48 / Chapter 2.3.2.2. --- Effect of β2-adrenoceptor agonist on lipolysis --- p.48 / Chapter 2.3.2.3. --- Effect of β-adrenoceptor agonists on lipolysis --- p.49 / Chapter 2.3.2.4. --- Effect of non-selective β-adrenoceptor agonist on lipolysis --- p.50 / Chapter 2.3.2.5. --- Effect of modulators of intracellular cyclic nucleotide monophosphate on lipolysis --- p.51 / Chapter 2.3.2.6. --- Effect of exogenously delivered nitric oxide on lipolysis --- p.52 / Chapter 2.3.2.7. --- Gene expression of β-adrenoceptors in white adipose tissue --- p.52 / Chapter 2.3.2.8. --- Protein expression of β-adrenoceptors in white adipose tissue --- p.53 / Chapter 2.3.3. --- Effect of Lingzhi (water-extract) treatment on lipolysis --- p.54 / Chapter 2.3.3.1. --- Determination of body weight --- p.54 / Chapter 2.3.3.2. --- Lipolytic effect of forskolin --- p.54 / Chapter 3. --- Peroxisome Proliferator-Activated Receptor-y (PPAR-γ) --- p.91 / Chapter 3.1. --- Introduction --- p.91 / Chapter 3.1.1. --- Peroxisome proliferator-activated receptors --- p.91 / Chapter 3.1.1.1. --- Peroxisome proliferator-activated receptor-γ --- p.91 / Chapter 3.1.1.1.1. --- "PPAR-γ in obesity, lipid metabolism and type 2 diabetes" --- p.91 / Chapter 3.1.1.1.2. --- PPAR-γ in inflammation and atherosclerosis --- p.92 / Chapter 3.1.1.2. --- PPAR-γ and thiazolidinediones --- p.93 / Chapter 3.2. --- Materials and method --- p.95 / Chapter 3.2.1. --- Materials --- p.95 / Chapter 3.2.1.1. --- Composition of physiological salt solution --- p.95 / Chapter 3.2.1.2. --- Materials used in lipolysis experiment --- p.95 / Chapter 3.2.1.3. --- Materials used in RT-PCR --- p.95 / Chapter 3.2.1.4. --- Materials used in Western blotting --- p.95 / Chapter 3.2.2. --- Methods --- p.96 / Chapter 3.2.2.1. --- Lipolysis experiment --- p.96 / Chapter 3.2.2.2. --- RT-PCR --- p.96 / Chapter 3.2.2.3. --- Western blotting --- p.97 / Chapter 3.3. --- Results --- p.97 / Chapter 3.3.1. --- Effect of PPAR-γ agonists on lipolysis --- p.97 / Chapter 3.3.2. --- Gene expression of PPAR-γ in white adipose tissue --- p.97 / Chapter 3.3.3. --- Protein expression of PPAR-γ in white adipose tissue --- p.97 / Chapter 4. --- 3-Hydoxy-3-MethylgIutaryl Coenzyme A (HMG-CoA) Reductase --- p.106 / Chapter 4.1. --- Introduction --- p.106 / Chapter 4.1.1. --- Cholesterol metabolism and cardiovascular diseases --- p.106 / Chapter 4.1.2. --- Statins --- p.106 / Chapter 4.1.2.1. --- Modes of action --- p.107 / Chapter 4.1.2.2. --- Therapeutic efficacy of statins --- p.108 / Chapter 4.1.2.2.1. --- Diabetes --- p.108 / Chapter 4.1.2.2.2. --- Coronary artery disease --- p.109 / Chapter 4.1.3. --- Distribution and expression of HMG-CoA reductase --- p.109 / Chapter 4.2. --- Materials and method --- p.110 / Chapter 4.2.1. --- Materials --- p.110 / Chapter 4.2.1.1. --- Composition of physiological salt solution --- p.110 / Chapter 4.2.1.2. --- Materials used in lipolysis experiment --- p.110 / Chapter 4.2.1.3. --- Materials used in RT-PCR --- p.110 / Chapter 4.2.1.4. --- Materials used in Western blotting --- p.110 / Chapter 4.2.2. --- Methods --- p.110 / Chapter 4.2.2.1. --- Lipolysis experiment --- p.110 / Chapter 4.2.2.2. --- RT-PCR --- p.111 / Chapter 4.2.2.3. --- Western blotting --- p.111 / Chapter 4.3. --- Results --- p.112 / Chapter 4.3.1. --- Effect of statins on lipolysis --- p.112 / Chapter 4.3.2. --- Gene expression of HMG-CoA reductase in various internal organs --- p.112 / Chapter 4.3.3. --- Protein expression of HMG-CoA reductase in various internal organs --- p.113 / Chapter 5. --- Discussion --- p.122 / Chapter 5.1. --- β-adrenoceptor-mediated lipolysis --- p.122 / Chapter 5.2. --- Studies on peroxisome proliferator-activated receptor-γ --- p.140 / Chapter 5.3. --- Studies on HMG-CoA reductase --- p.142 / Chapter 5.4. --- Further studies --- p.147 / Chapter 5.5. --- Conclusions --- p.148 / Chapter 6. --- References --- p.152

No description available.

The purpose of the quality improvement (QI) project was to examine the relationship between amended nursing education concerning diabetes mellitus (DM) Type 2 self-care management incorporating Tune in, Explore, Assist, Communicate, and Honor (TEACH) and Motivational Interviewing (MI) strategies and techniques and the Glycosylated hemoglobin (HgbA1C) of veteran patients with uncontrolled diabetes. The target sample included the 2 licensed practical nurses and 2 registered nurses assigned to 2 primary care teams, and the 10 purposively sampled patients with uncontrolled DM Type 2 from each team. The nurses' competencies were measured through descriptive comparison before and after nursing education implementation using the instrument Patient Education: TEACH for Success Self-Assessment Questionnaire. The nurses' confidence and their perceived importance of the TEACH and MI skills application and skill assessment for promoting health behavior change were tested inferentially with a paired t test before and after nursing education implementation using the instrument Clinician Importance and Confidence Regarding Health Behavior Counseling Questionnaire. The primary care team developed their skills tailored to each patient's needs, considering the guiding principles and premises of the health belief model (HBM). Patients' self-care management knowledge, skills and confidence were improved. The project decreased the elevated HgbA1C of patients measured after the project initiative. The QI project leads to positive social change by decreasing the number of patients with uncontrolled diabetes among the veteran population. The patients and their providers can develop individualized plans of care for diabetes management by educating, redirecting, and evoking behavioral changes in the veteran patients by using a team approach.