[Truncated abstract] Cardiovascular reflex control of the vasculature is important in maintaining adequate tissue oxygenation in the face of disturbances in physiological homeostasis. Alterations in blood oxygen levels and blood distribution evoke integrated neural, mechanical and humoral responses which modulate peripheral vasomotor tone to maintain systemic cardiovascular integrity. The balance between the local effects of hypoxia and changes in chemoreflex control of vascular tone during hypoxia determine whether net vasoconstriction or vasodilatation is evident in the peripheral vasculature. The mechanisms contributing to hypoxic vasodilatation per se have not previously been defined in healthy humans. Study 1 of this thesis (Chapter 3) investigated the mechanisms contributing to vasomotor responses to chemoreflex activation in the human forearm ... Study 2 (Chapter 4a) investigated the mechanisms controlling vasomotor responses to isocapnic hypoxia in subjects with type 2 diabetes ... Study 3 (Chapter 5) compared the vascular responses to decreased venous return in individuals with and without right atrial afferent innervation ... The results of this thesis indicate that in healthy humans isocapnic hypoxia induces sympathetic vasoconstriction, which masks underlying β-adrenoceptor mediated vasodilatation. The normal vasomotor response to isocapnic hypoxia is impaired in subjects with type 2 diabetes. Despite intact vasoconstrictor responses, subjects with type 2 diabetes exhibited attenuated adrenaline-mediated vasodilatation compared to healthy control subjects, suggesting that the chemoreflex in these subjects is ill-equipped to respond to hypoxic stress. In clinical terms, impaired reflex vasomotor

Thesis (M.D.)--University of Adelaide, Dept. of General Practice, 2005. / Includes publications published as a result of ideas developed in this thesis, inserted at end. "April 2005" Includes bibliographical references (leaves 210-242).

Thesis (M.S.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains xiii, 177 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 147-154).

Thesis (M.S.)--University of Michigan, 1991.

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains xiv, 287 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 261-282).

Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5301. Adviser: Eric Boerwinkle. Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1991.

Thesis (M.S.) --The University of North Carolina at Greensboro, 2008. / Directed by Martha Taylor; submitted to the Dept. of Nutrition. Title from PDF t.p. (viewed Apr. 13, 2010). Includes bibliographical references (p. 62-65).

Este trabalho teve como objetivo conhecer como se dão as interações familiares de adolescentes com diabetes tipo 1 desde o diagnóstico da doença.Utilizou-se como referencial metodológico a História Oral .Os dados coletados mediante entrevistas gravadas com sete adolescentes foram analisados à luz do Modelo Calgary para Avaliação da Família de Wright e Leahey.As narrativas demonstraram que apesar do acréscimo de atividades na rotina diária do adolescente e da família, relacionadas à manutenção e controle do diabetes, as interações familiares sofrem poucas modificações com a chegada da doença e que os conflitos entre os pais e o adolescente com diabetes não diferem tanto daqueles ocorridos entre os pais e adolescentes saudáveis.A superproteção foi um sentimento percebido pelos adolescentes após o surgimento da doença,pois os pais têm preocupações com complicações imediatas e em longo prazo. O principal vínculo demonstrado pelos adolescentes entrevistados com a suas famílias foi o vínculo de confiança. Para eles é muito importante saber que conquistaram a confiança de seus pais de que podem ter certa autonomia em relação ao manejo do diabetes.Com os irmãos compartilham superficialmente o diabetes,mesmo aqueles que mantêm relações mais estreitas.A família extensa também oferece contribuições em diferentes fases da doença. Os adolescentes entrevistados forneceram dados de que sua comunicação verbal com sua família é ampla e direta. Sentem-se livres e confiantes em falar abertamente sobre assuntos diversos com os pais e os outros membros que coabitam, relatando também com quem se relacionam melhor em casa. Percebe-se também que a família tenta de alguma maneira moldar-se de acordo com as necessidades da pessoa que tem diabetes,na organização e funcionamento.Sentimentos de gratidão são demonstrados pela associação especializada em educação em diabetes, citada como a responsável por todo ou grande parte do conhecimento adquirido,principalmente pelas atividades oferecidas no acampamento para jovens, e também como fonte de solução de problemas oriundos do diagnóstico do diabetes para os pais e para os próprios adolescentes. / This study aimed to understand how to give the family interactions of adolescents with type 1 diabetes since diagnosis of illness. The method used was Oral History y. Data collected through recorded interviews with seven adolescents were examined in the light of Wright e Leaheys Calgary Family Evaluation Model .Narratives demonstrated that despite the increased activities in the daily routine of the adolescent and family for care and control of diabetes, family interactions experience little change with the arrival of the illness and that conflicts between parents and adolescents with diabetes do not differ from those that occurred between parents and healthy adolescents. Overprotection was a sentiment felt by the teenagers after the onset of the disease because parents have concerns about immediate complications and long term. The main bond shown by the adolescents interviewed with their families was the bond of trust. Adolescents share the diabetes management with brothers superficially, even those who maintain more closed. Extended family also offers contributions in different stages of the disease. The adolescents interviewed communicate with your family is extensive and direct, feeling confident to talk about various issues with parents and other members, also reporting to whom they relate better at home. Family tries shape up according to the needs of the person who has diabetes, the organization and function.

The ability of insulin to stimulate glucose uptake into muscle and adipose tissue is central to the maintenance of whole-body glucose homeostasis. Deregulation of insulin action manifests itself as insulin resistance, a key component of type 2 diabetes. Insulin resistance is also observed in HIV patients receiving protease inhibitors. An agent that can reversibly induce an insulin-resistant state would be a very useful tool in developing model systems that mimic the pathogenesis of type 2 diabetes. Insulin resistance can arise from defects in insulin signal transduction, changes in the expression of proteins or genes that are targets of insulin action, cross talk from other hormonal systems or metabolic abnormalities. Deterioration of the insulin-receptor-signalling pathway at different levels leading to decreased levels of signalling pathway intermediates and/or decreased activation through phosphorylation accounts for the evolution from an insulin-resistant state to type 2 diabetes. In addition, defects in GLUT4 glucose transporter translocation are observed, further fuelling impairments in skeletal muscle glucose uptake. Levels of insulin-induced GLUT4 translocation in the skeletal muscle of type 2 diabetic patients are typically reduced by 90%. Many cellular pathways & their intermediates are in some way or another linked to insulin signalling. This study focused on three of these namely the PI3-kinase/Akt pathway, the Mitogen Activated Protein Kinase (MAPK) cascade and the AMP Kinase pathway, with successful monitoring of the PI3-K pathway. Investigations involved observing and evaluating the effects of various compounds as well as an indigenous medicinal plant, Sutherlandia frutescens on the activities of key insulin signalling pathway intermediates within the three fore mentioned pathways including Akt, AMPK and MEK1/2 as well as membrane surface GLUT4 levels. Scientific research has in the past leant heavily on Western blotting as the method of choice for gaining vital information relating to signal transduction pathways, however for research into cellular mechanisms the negatives of this method outweigh the positives. The drawbacks include a need for large amount of cells, multiple washing steps which may be disadvantageous to any weak and transient interactions as well as lysing of cells which may interfere with the maintenance of the subcellular localisation of a specific signalling event. Based on these, the need for a better method in terms of speed & reliability to monitor phosphorylation states of signal transduction pathway intermediates & GLUT4 translocation was evident and was one VII of the main aims & successes of this study. The method created used the mouse muscle cell line C2C12 in conjunction with the quick, sensitive method of flow cytometry which allowed us to monitor these processes in these cells through immune-labelling. Adherent cell cultures such as the C2C12 cell line pose the problem of possible damage to plasma membrane receptors (including insulin receptors) during harvesting to obtain a cell suspension for flow cytometry. We however used C2C12 mouse myocytes to optimize a method yielding insulin responsive cells in suspension that were successfully used for flow cytometry after immunelabelling of insulin signalling intermediates. Insulin (0.1μM) significantly raised the levels of both P-Akt and GLUT4 above basal levels. This effect was shown to be dose dependent. At a concentration of 50μg/ml, Sutherlandia frutescens was able to act as an insulin-mimetic in terms of its ability to increase P-Akt levels, GLUT4 translocation and glucose utilisation in an acute manner. These increases could be reduced with the addition of wortmannin, a PI3-K inhibitor. Therefore, these results suggest the mechanism of the plant extract’s insulin-like activity may be in part due to the activation of the insulin signalling pathway leading to GLUT4 translocation, which involves the phosphorylation of insulin receptor- and subsequent PI3-K activity, leading to P-Akt activity. These results provide further evidence of this plant extract’s anti-diabetic potential. The effect of Sutherlandia frutescens on insulin secretion, calcium signalling and proliferation in INS-1 rat pancreatic cells was also investigated and it was found to increase the activities of all of these processes. However no change in the levels of GLUT2 glucose transporter was seen. Ritonavir is prescribed by the South African Department of Health in co-formulation with other protease inhibitors within its second regime in the treatment of HIV and AIDS. Using C2C12 cells, ritonavir decreased glucose uptake acutely and had no effect on GLUT4 translocation however surprisingly increased P-Akt levels. In conclusion, it was found that Sutherlandia frutescens has antidiabetic benefits, diverse in nature depending on tissue type as well as length of time administered. The establishment of novel flow cytometry techniques to assess antidiabetic properties using in vitro cell culture was achieved. These methods will be useful in the future for the assessment of insulin sensitivity and in the identification of novel compounds that stimulate the insulin signalling pathways.