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Copies of author's previously published articles inserted behind back end-papers. Bibliography: leaves 139-160. Identifies and characterises specific residues of biGFBP-2 that comprises the IGF binding site.

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on November 19, 2009). Thesis advisor: Dr. Thyfault. Includes bibliographical references.

Insulin receptor (IR) exists in two isoforms (IR-A and IR-B), which differ in the tissue distribution and probably also in their function, i.e. in their response to insulin binding. It is supposed that IR-A activates mainly mitogenic processes and that IR-B triggers mainly metabolic effects resulting in the uptake of glucose by muscle and fat cells. Insulin can also weakly bind to the receptor for IGF-1 (IGF-1R), a growth factor involved in the regulation of growth and development. Insulin derivatives selectively binding only to one of the receptors would be interesting for the study of the receptors but also potentially for the treatment of diseases such as diabetes or cancer. Here we used our experience in the structure-activity studies of insulin for the design, synthesis and biological characterization of 4 new insulin derivatives in order to modify their selectivity towards the individual receptors. We systematically modified insulin by amidation of the C-terminus of its B-chain or by prolongation of the B-chain by 1-3 carboxyamidated glycine residues. Binding affinities of all new analogues for IR-A and IR-B were determined and for some of the analogues binding affinities for IGF-1R as well. Finally, abilities of analogues to activate autophosphorylation of intracellular subunits of IR-A and...

Introduction: Metabolic syndrome and depression are considered to be important risk factors for the development of cardiovascular diseases. The prevalence of metabolic syndrome is estimated to be around 25% of the adult population in industrialized countries, including the population of Czech Republic. The prevalence of depression is estimated to be around 15% of the same adult population. It is not clear yet on the base of poor literature, which is so far available, whether there is a causal relationship between these factors or not. Objective: To try to find a relationship between metabolic syndrome and depression in a population sample using clinical and metabolic parameters. Methods: The prevalence of depressivity or other psychopathologies was evaluated with the use of self-report questionnaires in a randomly selected population sample of 259 people living in Pilsen. The questionnaires were mailed to the subjects. Those of them who responded were invited to the examination of anthropometric and laboratory parameters defining the metabolic syndrome and to the examination of some other parameters. The occurrence of risk factors of the metabolic syndrome of insulin resistance and the relationship between depression and metabolic syndrome was investigated. Metabolic syndrome of insulin resistance...

This thesis deals with the analysis of eating habits of seniors with Diabetes mellitus type 2. Many seniors with Diabetes mellitus type 2 are introduced to a proper diet either through their Doctor or a nutrition therapist. This diabetic diet assists them in maintaining proper blood glucose levels and helps prevent a variety of diabetic complications. Many diabetics, who understand their illness, begin to make changes in their lifestyles that will help them in the future. More thought is put into their lifestyle and how to improve their quality of life. For example, many diabetics become more active, begin to be more diligent with their dietary choices and discover a new meaning of life.

Made available in DSpace on 2015-12-06T23:47:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2007 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A pineal é aceita como reguladora da reprodução em mamíferos, por sua capacidade de interagir com as gonadotrofinas e influenciar as gônadas e promover a ciclicidade estral em algumas espécies. Contudo, sua função em espécies não foto-periódicas (camundongo, rato, macaco e ser humano) ainda não está totalmente esclarecida. Por este motivo, propusemo-nos a avaliar a histomorfologia e a histomorfometria do sistema reprodutor (ovários e útero), bem como os níveis plasmáticos de IGF-I e dos esteróides sexuais em ratas pinealectomizadas ou mantidas sob estímulo luminoso contínuo e após o tratamento com melatonina. Foram utilizadas ratas albinas, adultas, virgens, pesando aproximadamente 250g, da linhagem EPM - 1 Wistar. As ratas foram divididas, aleatoriamente, em seis grupos, a saber: GI – controle, tratado com veículo (n=20); GII – falsamente pinealectomizado, sham, tratado com veículo (n=20); GIII – pinealectomizado e tratado com veículo (n=20); GIV - pinealectomizado e tratado com melatonina (n=20); GV - submetido à luz contínua e tratado com veículo (n= 20); GVI – submetido à luz contínua e tratado com melatonina (n=20). O tratamento com melatonina (GIV e GVI) foi realizado por 90 dias consecutivos. Na noite anterior ao término do estudo, os animais foram colocados em gaiolas metabólicas, coletandose a urina noturna. Posteriormente, o sangue foi retirado pelo plexo ocular nos animais para determinação hormonal. Em seguida, as ratas foram sacrificadas e os ovários e o útero foram removidos para análise histomorfológica e histomorfométrica. Observou-se que a redução dos níveis séricos da melatonina (pela pinealectomia ou luz contínua, grupos III e V, respectivamente) determinou elevação sérica de estrogênio e redução significante de progesterona e IGF-I. Já a reposição com melatonina, reverteu este estado nos animais pinealectomizados, mas não nos animais sob luz contínua (grupo VI). Houve diminuição dos níveis androgênicos nos animais que receberam melatonina (grupos IV e VI) em relação os animais com baixos níveis de melatonina (grupos III e V). A diminuição sérica de melatonina (grupos III e V) determinou a proliferação do endométrio. Este efeito não foi totalmente bloqueado nos animais submetidos à luz contínua ou à pinealectomia e que foram tratados com melatonina. A diminuição dos níveis de melatonina determina alterações histomorfológicas e histomorfométricas nos ovários, sendo que a reposição de melatonina restaura essas modificações nos folículos ovarianos, bem como no epitélio e no estroma (células intersticiais). Contudo, o efeito desse hormônio tem menor impacto no epitélio superficial do ovário dos animais sob luz contínua. Nossos dados sugerem que a melatonina interfere com a produção hormonal e o sistema reprodutor, mas não é efetiva em animais sob luz contínua; possivelmente outros mecanismos que possam estar envolvidos sejam independentes da pineal. / The pineal gland is accepted as the reproduction modulator in mammals but its function in non-photoperiodic species (mouse, rat and primate) is still not thoroughly clear considering the endocrine interactions are fairly complex. For this reason, we have proposed to evaluate the histomorphology of the reproductive system (ovary and uterus) as well as the plasmatic levels of IGF-I and the sexual steroids in pinealectomized female rats or kept under continuous luminous stimulus and after the treatment using melatonin. The albino virgo female rats weighed approximately 250g from the EPM lineage – 1 Wistar were randomly divided into six groups: GI – control treated with vehicle (n=20); GII – falsely pinealectomized, sham, and treated with vehicle (n=20); GIII – pinealectomized and treated with vehicle (n=20); GIV – pinealectomized and treated with melatonin (n=20); GV – submitted to continuous light and treated with vehicle (n=20); GVI – submitted to continuous light and treated with melatonin (n=20). The treatment using melatonin for these groups lasted 90 consecutive days. The night before the end of the study, the animals were put in metabolic cages to collect urine. Later, the blood was taken through the ocular plexus for the hormonal determination. Then, both the ovary and the uterus of the female rats were removed for a histomorphological and histomorphometric analyses. The reduction of the serum levels of melatonin (pinealectomy or continuous light) as followed by an increase in estrogen levels and a significant reduction in progesterone and IGF-I blood levels. Differently, the replacement with melatonin reverted this condition in the pinealectomized animals but this did not happen with the animals exposed to continuous light. There was a reduction in the androgenic levels when compared to animals with low levels of melatonin. The reduction in serum melatonin is related to the endometrial proliferation. This effect is not totally blocked in animals submitted to continuous light or pinealectomy, which were treated with melatonin. Also, the decrase in the melatonin levels determined histomorphologic changes in the ovaries and the melatonin replacement restored these alterations in the ovarian follicle as well as in the epithelium and in the ovarian stroma (interstitial cells). Nevertheless, the effect of this hormone has a smaller impact in the ovarian superficial epithelium in animals under continuous light. Our data suggest that melatonin interferes with the hormone production and the reproductive system, but this is not the case in animals under continuous light; it is possible that other mechanisms, which may be involved are regardless of the pineal. / BV UNIFESP: Teses e dissertações

O efeito de refeições ricas em carboidratos e lipídeos sobre a sensibilidade à insulina foi avaliado. Além disso, investigou-se o conteúdo da proteína GLUT4 em músculo esquelético e tecido adiposo branco. Ratos foram realimentados por 1, 2, 4 e 6 horas com: refeição balanceada (B); rica em carboidrato (C) e rica em lipídeo (L). O índice glicose/insulina revelou que C e L apresentavam resistência à insulina 2 horas após o início da ingestão. No teste de tolerância à insulina, uma redução (~47%) na sensibilidade à insulina foi observada em C após 2 e 4 horas de realimentação. O teste de tolerância à glicose confirmou a resistência à insulina em C e L após 2 horas de ingestão. Não houve alteração no conteúdo de GLUT4, nos momentos em que se verificou alteração na sensibilidade à insulina. Tais resultados indicam que, em ratos, refeições não balanceadas (alto teor de carboidrato ou alto teor de lipídeo), induzem menor sensibilidade à insulina 2 horas após o início da ingestão, e este fenômeno não envolve alterações no conteúdo de GLUT4 nos tecidos avaliados. / The effect of high carbohydrate and fat meals on the insulin sensitivity was evaluated. Furthermore, it was investigated the content of GLUT4 protein on the skeletal muscle and white adipose tissue. Rats were refed for 1, 2, 4 and 6 hours with: balanced meal (B); high carbohydrate meal (C) and high fat meal (L). The glucose/insulin index shows that C and L meals exhibited insulin resistance after 2 hours of ingestion. In the insulin tolerance test, a reduction (~47%) in the insulin sensitivity was observed in C group after 2 and 4 hours of refeeding. The glucose tolerance test confirmed the insulin resistance in C and L-groups after 2 hours of ingestion and such phenomena did not involve alterations in the GLUT4 content on both skeletal muscle or white adipose tissue.

Made available in DSpace on 2014-06-11T19:22:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-01-27Bitstream added on 2014-06-13T20:27:33Z : No. of bitstreams: 1 pintojunior_dac_me_prud_prot.pdf: 1186583 bytes, checksum: e83d66af1d0fd4767ad1c9b69a60014b (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A obesidade é uma condição que afeta muitos indivíduos e está relacionada a vários tipos de disfunções,como a resistência insulínica.Esta patologiase dá devido a uma falha na sinalização entre o hormônio, proteínas intracelularese o GLUT4 em células musculares e adiposas. Alguns fatores contribuem para aumentar esta falha, como o aumento da fosforilação em serinado IRS –1 e atividade pró -inflamatória. Uma maneira indireta de se avaliar o grau de inflamação é analisar a expressão do SOCS3,que estámais expressoquando há maior atividade inflamatória. Aprática de exercício físico aparece como uma importante ferramenta, pois melhora a sensibilidade insulínica e pode aumentara expressão do transportador de glicose até mesmo em animais obesos. Oobjetivo do trabalho foiavaliar o efeito dos exercícios aeróbio contínuo e com pesoscombinadossobre a via de sinalização da insulina e expressão de transportador... / Obesity is a condition that affects manypeople and is related with some kindof diseases, like insulin resistance.This pathology occurs because of animpairmenton activation of GLUT4 machinery (insulin signaling, activation of intracellular proteins) in skeletal muscle and adipose tissue. Some factors contributedirectly with this illness, like increase IRS –1 serinephosphorylationand pro –inflammatoryactivity. An indirect way to measure inflammation istoanalyze expression of SOCS3, because when it is overexpressed means thatthere are more pro –inflammatory activity.Literature shows that physical exercise can improve insulin sensitivity by increases of GLUT4 expression even in obese rats. So we aimed... (Complete abstract click electronic access below)

Made available in DSpace on 2014-10-09T12:38:49Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:59:43Z (GMT). No. of bitstreams: 1 02813.pdf: 2047482 bytes, checksum: f4697322c53a019aad9b8eaba41372a8 (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP