Página 1 dos resultados de 42536 itens digitais encontrados em 0.025 segundos

‣ Estudo dos mecanismos envolvidos na redução da sensibilidade à insulina decorrente da restrição crônica de sal: o sistema nervoso simpático e a via 1-arginina - óxido nítrico; Study of the mechanisms of the lower insulin sensitivity due to chronic salt restriction: the sympathetic nervous system and the l-arginine - nitric oxide pathway

Ruivo, Gilson Fernandes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 31/03/2003 Português
Relevância na Pesquisa
36.553423%
A restrição crônica de sal na dieta tem sido recomendada como medida não medicamentosa do tratamento da hipertensão arterial sistêmica. Entre os efeitos observados desta medida terapêutica tem sido descrita uma redução dos valores da pressão arterial (PA), tanto em indivíduos normotensos e pacientes hipertensos, assim como em animais de laboratório. Outros efeitos observados são alterações do metabolismo de carboidratos e de lípides. Tanto em indivíduos normotensos e pacientes hipertensos, assim como em animais de laboratório foram observadas maiores concentrações de peptídeo C e de insulina, sem alteração da glicemia e com redução da captação periférica de glicose pelos tecidos, caracterizando um estado de resistência à insulina. No metabolismo de lípides, uma outra conseqüência da restrição crônica de sal é a maior concentração plasmática de colesterol total e triacilgliceróis. Apesar da demonstração dos efeitos do sal sobre o metabolismo de carboidratos e lípides em humanos e animais existem dados conflitantes na literatura, com resultados opostos a estes descritos. Para melhor compreensão deste fenômeno, foi desenvolvido um estudo em nosso laboratório, o qual demonstrou que ratos Wistar machos que receberam restrição crônica de sal na dieta apresentaram maiores insulinemias medidas durante um teste de tolerância à glicose e sem a constatação de resistência à insulina em adipócitos isolados avaliada pela EC50 Entretanto...

‣ Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

Pimenta, W.P.; Santos, M.L.; Cruz, N.S.; Aragon, Flávio Ferrari; Padovani, C.R.; Gerich, J.E.
Fonte: Associação Brasileira de Divulgação Científica (ABRADIC) Publicador: Associação Brasileira de Divulgação Científica (ABRADIC)
Tipo: Artigo de Revista Científica Formato: 301-308
Português
Relevância na Pesquisa
36.56226%
To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml...

‣ Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats

Reis, Marise A.B.; Carneiro, Everardo M.; Mello, Maria A.R.; Boschero, A. Carlos; Saad, Mario J. A.; Velloso, Licio A.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 403-410
Português
Relevância na Pesquisa
36.585908%
Malnutrition is related to diabetes in tropical countries. In experimental animals, protein deficiency may affect insulin secretion. However, the effect of malnutrition on insulin receptor phosphorylation and further intracellular signaling events is not known. Therefore, we decided to evaluate the rate of insulin secretion and the early molecular steps of insulin action in insulin-sensitive tissues of an animal model of protein deficiency. Pancreatic islets isolated from rats fed a standard (17%) or a low (6%) protein diet were studied for their secretory response to increasing concentrations of glucose in the culture medium. Basal as well as maximal rates of insulin secretion were significantly lower in the islets isolated from rats fed a low protein diet. Moreover, the dose-response curve to glucose was significantly shifted to the right in the islets from malnourished rats compared with islets from control rats. During an oral glucose tolerance test, there were significantly lower circulating concentrations of insulin in the serum of rats fed a low protein diet in spite of no difference in serum glucose concentration between the groups, suggesting an increased peripheral insulin sensitivity. Immunoblotting and immunoprecipitation were used to study the phosphorylation of the insulin receptor and the insulin receptor substrate-1 as well as the insulin receptor substrate-1-p85 subunit of phosphatidylinositol 3-kinase association in response to insulin. Values were greater in hind-limb muscle from rats fed a low protein diet compared with controls. No differences were detected in the total amount of protein corresponding to the insulin receptor or insulin receptor substrate-1 between muscle from rats fed the two diets. Therefore...

‣ Protein deficiency and nutritional recovery modulate insulin secretion and the early steps of insulin action in rats

Latorraca, Márcia Q.; Reis, Marise A. B.; Carneiro, Everardo M.; Mello, Maria A. R.; Velloso, Licio A.; Saad, Mario J. A.; Boschero, A. Carlos
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1643-1649
Português
Relevância na Pesquisa
36.56226%
Maternal malnutrition was shown to affect early growth and leads to permanent alterations in insulin secretion and sensitivity of offspring. In addition, epidemiological studies showed an association between low birth weight and glucose intolerance in adult life. To understand these interactions better, we investigated the insulin secretion by isolated islets and the early events related to insulin action in the hind-limb muscle of adult rats fed a diet of 17% protein (control) or 6% protein [low (LP) protein] during fetal life, suckling and after weaning, and in rats receiving 6% protein during fetal life and suckling followed by a 17% protein diet after weaning (recovered). The basal and maximal insulin secretion by islets from rats fed LP diet and the basal release by islets from recovered rats were significantly lower than that of control rats. The dose-response curves to glucose of islets from LP and recovered groups were shifted to the right compared to control islets, with the half-maximal response (EC 50) occurring at 16.9 ± 1.3, 12.4 ± 0.5 and 8.4 ± 0.1 mmol/L, respectively. The levels of insulin receptor, as well as insulin receptor substrate-1 and phosphorylation and the association between insulin receptor substrate-1 and phosphatidylinositol 3-kinase were greater in rats fed a LP diet than in control rats. In recovered rats...

‣ Low ethanol consumption induces enhancement of insulin sensitivity in liver of normal rats

Furuya, Daniela Tomie; Binsack, Ralf; Onishi, Mary Emy; Seraphim, Patricia Monteiro; Machado, Ubiratan Fabres
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1813-1824
Português
Relevância na Pesquisa
36.56226%
Moderate amounts of alcohol intake have been reported to have a protective effect on the cardiovascular system and this may involve enhanced insulin sensitivity. We established an animal model of increased insulin sensitivity by low ethanol consumption and here we investigated metabolic parameters and molecular mechanisms potentially involved in this phenomenon. For that, Wistar rats have received drinking water either without (control) or with 3% ethanol for four weeks. The effect of ethanol intake on insulin sensitivity was analyzed by insulin resistance index (HOMA-IR), intravenous insulin tolerance test (IVITT) and lipid profile. The role of liver was investigated by the analysis of insulin signaling pathway, GLUT2 gene expression and tissue glycogen content. Rats consuming 3% ethanol showed lower values of HOMA-IR and plasma free fatty acids (FFA) levels and higher hepatic glycogen content and glucose disappearance constant during the IVITT. Neither the phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), nor its association with phosphatidylinositol-3-kinase (PI3-kinase), was affected by ethanol. However, ethanol consumption enhanced liver IRS-2 and protein kinase B (Akt) phosphorylation (3 times...

‣ Dieta de cafeteria induz obesidade, resistência periférica a insulina, e reduz a secreção deste hormônio por ilhotas de ratas : restauração do processo secretório, mas não da sensibilidade à insulina durante a prenhez; Cafeteria diet induces obesity, peripheral insulin resistance, and reduces insulin secretion in isolated from rats : restoration of the secretory process but not of the insulin sensibility during pregnancy

Emerielle Cristine Vanzela
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 31/03/2010 Português
Relevância na Pesquisa
36.548313%
A obesidade atingiu proporções alarmantes constituindo-se num fator de risco para o desenvolvimento de várias doenças. O aumento da resistência periférica à insulina acompanha esta patologia e a incapacidade da célula beta pancreática em suprir a maior necessidade por insulina leva ao desenvolvimento de intolerância à glicose, hiperglicemia e diabetes. Por esta razão, é importante investigar mecanismos que tornem a célula beta capaz de aumentar sua capacidade secretória. A exemplo da obesidade, resistência periférica à insulina é também observada durante a prenhez. No entanto, neste caso, a célula beta é capaz de aumentar a produção e secreção do hormônio, mantendo a tolerância à glicose em condições adequadas. Diante disso,decidimos investigar a sensibilidade à insulina e a consequente resposta das células beta pancreáticas durante a prenhez em ratas obesas. Observamos que a alimentação com a dieta de cafeteria aumentou o ganho de peso, bem como os depósitos de gordura das ratas. Ratas obesas não-prenhes (Caf) e prenhes (CafP) apresentaram tolerância à glicose diminuída, associada a um aumento da insulina plasmática em resposta à sobrecarga de glicose no grupo CafP. Apesar disso, as glicemias de jejum e pós-prandial foram normais nos dois grupos. No entanto...

‣ Secreção e ação da insulina em camundongos knockout para o receptor de LDL (LDLR -/-) alimentados com dieta padrão ou hiperlipídica; Secretion and action of the insulin on LDL receptor knockout mice (LDLR -/-) fed with chow or hyperlipidic diet

Jane Cristina de Souza
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 2012/03/3 Português
Relevância na Pesquisa
36.548313%
Alterações no conteúdo de colesterol celular podem contribuir para o mau funcionamento das células-beta pancreáticas. Camundongos knockout para o receptor de LDL (LDLR-/-) possuem maior teor de colesterol nas ilhotas pancreáticas e secretam menos insulina em comparação a camundongos selvagens (WT). Neste estudo, investigamos a associação entre o conteúdo de colesterol, a secreção de insulina e a movimentação de cálcio citoplasmático nessas ilhotas. Além disso, analisamos o efeito da dieta rica em gordura (HFD) sobre a homeostasia glicêmica, secreção e ação da insulina nesses camundongos. Os resultados mostraram que a primeira e segunda fase de secreção de insulina assim como a movimentação de Ca2+, estimuladas por glicose, foram reduzidas nos LDLR-/-. Camundongos LDLR-/- também apresentaram menor conteúdo de proteínas envolvidas com a extrusão dos grânulos de insulina tais como: VAMP-2 e SNAP-25 (p<0,05). A remoção do excesso de colesterol pelo uso da metil-beta-ciclodextrina (M?CD) normalizou a secreção de insulina, estimulada por glicose (GSIS) ou tolbutamida, assim como a movimentação de cálcio estimulada por glicose. A remoção do colesterol das ilhotas WT com 0.1 e 1 mmol/L de M?CD reduziu a secreção bem como a movimentação de cálcio. No entanto...

‣ Insulin secretion, insulin sensitivity, and hepatic insulin extraction in first-degree relatives of type 2 diabetic patients

Pimenta,W.P.; Santos,M.L.; Cruz,N.S.; Aragon,F.F.; Padovani,C.R.; Gerich,J.E.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2003 Português
Relevância na Pesquisa
36.56226%
To identify early metabolic abnormalities in type 2 diabetes mellitus, we measured insulin secretion, sensitivity to insulin, and hepatic insulin extraction in 48 healthy normal glucose-tolerant Brazilians, first-degree relatives of type 2 diabetic patients (FH+). Each individual was matched for sex, age, weight, and body fat distribution with a person without history of type 2 diabetes (FH-). Both groups were submitted to a hyperglycemic clamp procedure (180 mg/dl). Insulin release was evaluated in its two phases. The first was calculated as the sum of plasma insulin at 2.5, 5.0, 7.5, and 10.0 min after the beginning of glucose infusion, and the second as the mean plasma insulin level in the third hour of the clamp procedure. Insulin sensitivity index (ISI) was the mean glucose infusion rate in the third hour of the clamp experiment divided by the mean plasma insulin concentration during the same period of time. Hepatic insulin extraction was determined under fasting conditions and in the third hour of the clamp procedure as the ratio between C-peptide and plasma insulin levels. FH+ individuals did not differ from FH- individuals in terms of the following parameters [median (range)]: a) first-phase insulin secretion, 174 (116-221) vs 207 (108-277) µU/ml...

‣ Differential activation of insulin receptor substrates 1 and 2 by insulin-like growth factor-activated insulin receptors

Denley, A.; Carroll, J.; Brierley, G.; Cosgrove, L.; Wallace, J.; Forbes, B.; Roberts, C.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
Relevância na Pesquisa
36.548313%
The insulin-like growth factors (insulin-like growth factor I [IGF-I] and IGF-II) exert important effects on growth, development, and differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. The insulin receptor (IR) is structurally related to the IGF-IR, and at high concentrations, the IGFs can also activate the IR, in spite of their generally low affinity for the latter. Two mechanisms that facilitate cross talk between the IGF ligands and the IR at physiological concentrations have been described. The first of these is the existence of an alternatively spliced IR variant that exhibits high affinity for IGF-II as well as for insulin. A second phenomenon is the ability of hybrid receptors comprised of IGF-IR and IR hemireceptors to bind IGFs, but not insulin. To date, however, direct activation of an IR holoreceptor by IGF-I at physiological levels has not been demonstrated. We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II. The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal-regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis. These findings suggest that IGF-I can function directly through the IR and that the observed effects of IGF-I on insulin sensitivity may be the result of direct facilitation of insulin action by IGF-I costimulation of the IR in insulin target tissues.; Adam Denley...

‣ Structural basis for the lower affinity of the insulin-like growth factors for the insulin receptor

Gauguin, L.; Klaproth, B.; Sajid, W.; Andersen, A.; McNeil, K.; Forbes, B.; De Meyts, P.
Fonte: Amer Soc Biochemistry Molecular Biology Inc Publicador: Amer Soc Biochemistry Molecular Biology Inc
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
Relevância na Pesquisa
36.57589%
Insulin and the insulin-like growth factors (IGFs) bind with high affinity to their cognate receptor and with lower affinity to the noncognate receptor. The major structural difference between insulin and the IGFs is that the IGFs are single chain polypeptides containing A-, B-, C-, and D-domains, whereas the insulin molecule contains separate A- and B-chains. The C-domain of IGF-I is critical for high affinity binding to the insulin-like growth factor I receptor, and lack of a C-domain largely explains the low affinity of insulin for the insulin-like growth factor I receptor. It is less clear why the IGFs have lower affinity for the insulin receptor. In this study, 24 insulin analogues and four IGF analogues were expressed and analyzed to explore the role of amino acid differences in the A- and B-domains between insulin and the IGFs in binding affinity for the insulin receptor. Using the information obtained from single substituted analogues, four multiple substituted analogues were produced. A "quadruple insulin" analogue ([Phe(A8), Ser(A10), Thr(B5), Gln(B16)]Ins) showed affinity as IGF-I for the insulin receptor, and a "sextuple insulin" analogue ([Phe(A8), Ser(A10), Thr(A18), Thr(B5), Thr(B14), Gln(B16)]Ins) showed an affinity close to that of IGF-II for the insulin receptor...

‣ Testing the plasticity of insulin secretion and β-cell function in vivo: responses to chronic hyperglycaemia in the sheep; Testing the plasticity of insulin secretion and beta-cell function in vivo: responses to chronic hyperglycaemia in the sheep

Gatford, K.; De Blasio, M.; How, T.; Harland, M.; Pearce, B.; Owens, J.
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
Relevância na Pesquisa
36.553423%
Plasticity of insulin secretion is essential to maintain the action of insulin during insulin resistance and to prevent diabetes. Investigation of the plasticity of insulin secretion and its regulation is challenging, and the objective of this study was to develop a novel large-animal-based model. The effect of chronic moderate hyperglycaemia on the plasticity of insulin secretion, β-cell mass and function was determined in sheep. Adolescent sheep (120 days old) were infused with 25% glucose for 16 days to increase blood glucose by 50% (n = 10), and control animals (n = 9) were infused with saline. Glucose- and arginine-stimulated insulin secretion, insulin sensitivity and glucose effectiveness were measured in vivo before and during treatment (days 10–14), and β-cell mass was measured at the end of treatment. Hyperglycaemia increased blood glucose (+53%) and plasma insulin (+403%; each P < 0.003) and did not alter whole-body insulin sensitivity. Hyperglycaemia increased glucose-stimulated insulin secretion (particularly second phase; five-fold) and arginine-stimulated insulin secretion (particularly first phase; four-fold). Hyperglycaemia reduced β-cell mass (∼50%, P = 0.038) and increased glucose- and arginine-stimulated insulin secretion relative to β-cell mass five-fold (P = 0.060) and 20-fold (P = 0.007)...

‣ Role of microRNA in early life placental programming of insulin resistance and metabolic health.

Harryanto, Himawan
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2014 Português
Relevância na Pesquisa
36.57589%
Intrauterine growth restriction (IUGR) is associated with insulin resistance and diabetes, particularly later in adult life. Placental restriction is a common cause of IUGR, this condition induces insulin resistance and/ or insulin deficiency and consequently, impaired glucose tolerance in offspring, in the sheep and rat. Reduced expression of insulin signalling genes and that of their key metabolic targets in insulin sensitive tissues and of some molecular determinants of pancreatic β-cell insulin secretion and mass, contributes to impaired insulin action in offspring, in experimental and human IUGR. However, the underlying molecular mechanisms whereby IUGR alters the molecular profile of insulin sensitive and secreting tissues in later life are largely unknown. The studies described in this thesis examine the potential role of microRNAs (miRNAs) in the developmental programming of impaired insulin action in IUGR offspring. MiRNAs are short single-stranded RNAs (22 nucleotide in length), which are able to reduce the translation and/or abundance of mRNA and protein of targets. Each miRNA is predicted to regulate the abundance of many targets in co-ordinated networks to modify function, providing a potentially powerful pathway for developmental programming to influence later phenotype. Here...

‣ Regulation der Lipolyse im Fett- und im Muskelgewebe - Bedeutung für die Pathogenese der Insulinresistenz : Klinische Untersuchungen mit der Mikrodialyse; Regulation of lipolysis in adipose and skeletal muscle - significance of the pathogenesis of insulin resistance : Clinical study with the microdialysis technique

Hauer, Bastian
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.578672%
Einleitung: In der Pathogenese des Typ 2 Diabetes spielen einerseits eine reduzierte Insulinsekretion des Pankreas und andererseits eine gestörte insulinabhängige Glukoseverwertung der Skelettmuskulatur eine wichtige Rolle. Man nimmt an, dass bei der Entwicklung der Insulinresistenz eine Dysregulation des Lipidstoffwechsels von besonderer Bedeutung ist. Diese Störung im Lipidstoffwechsel kann das Resultat einer vermehrten Lipolyse und/oder einer verminderten Insulin-vermittelten Antilipolyse sein. Im Skelettmuskel lassen sich Lipidakkumulationen nachweisen. Somit könnte die Skelettmuskulatur als ein drittes Kompartiment der Fettverteilung neben dem viszeralen und subkutanen Fettgewebe angesehen werden. Ziel dieser Arbeit war es zu überprüfen, ob das muskuläre Fett metabolisch aktiv ist, wie diese Lipide durch Insulin hormonell reguliert werden und ob Unterschiede zu dem subkutanen Fettgewebe existieren. Dabei war zusätzlich von besonderem Interesse, ob Unterschiede in der Regulation der Lipolyse bei Personen mit Insulinresistenz im Vergleich zu insulinsensiblen Personen vorhanden sind. Methodik: Um die Regulation und die Aktivität der Lipolyse bestimmen zu können, wurde die Methodik der Mikrodialyse-Technik eingesetzt und aus dem gewonnenen Dialysat Glyzerol unter standardisierten Bedingungen (vor...

‣ Effekte einer kurzfristigen kohlenhydratreichen Ernährung auf die Insulinsensitivität und den intramyozellulären Lipidgehalt bei gesunden Nachkommen von Typ 2 Diabetikern; Effects of short-term high-carbohydrate nutrition on insulin sensitivity and intramyocellular lipids in healthy descendents of type 2 diabetics

Constantinidou, Evgenia
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.572888%
Bei der Pathogenese des Diabetes mellitus Typ 2 stehen sowohl Störungen im Kohlenhydrat- als auch im Lipidstoffwechsel im Vordergrund. Dies macht sich u.a. in einer gestörten Insulinsekretion der ß-Zellen sowie in einer Insulinresistenz der peripheren Zielgewebe bemerkbar. Es gibt zunehmend Hinweise für eine Beteiligung von ektopen Lipiden an der Insulinresistenz. Insbesondere die Speicherung und Akkumulation von Lipiden in der Skelettmuskelzelle, welche neben dem viszeralen und subkutanen Kompartiment als das neue dritte Lipidkompartiment angesehen wird, wird aktuell als ein Surrogat für biochemische Prozesse diskutiert, welche die Insulinsensitivität herabsetzen. Vorhergehende Studien konnten zeigen, dass eine langanhaltende Glukose-Infusion an Ratten, neben der Anhäufung von Triglyzeriden im Rattenskelettmuskel, zur Insulinresistenz führt. Die Auswirkungen eines Übermasses an Kohlenhydraten in der Ernährung beim Menschen werden bislang kontrovers dikutiert. Ziel: In der vorliegenden Studie sollte deshalb die Auswirkung einer kurzfristigen Kohlenhydrat-Überversorgung auf die Insulinresistenz und den intramyozellulären Lipidgehalt bei gesunden Normalpersonen untersucht werden. Es stellte sich auch die Frage, ob eine direkte Beziehung zwischen dem IMCL und der Insulinsensitivität bestand. Außerdem sollte überprüft werden...

‣ Untersuchungen zur Regulation der Phosphorylierung des Insulin-Rezeptor-Substrates-1 an Serin 318; Exploring regulation of phosphorylation in insulin-receptor-substrate-1 at serine 318

Fiedler, Hendrik
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.569639%
Die genauen molekularen Mechanismen der Insulinresistenz, welcher eine bedeutende Rolle bei der Pathogenese des Diabetes mellitus Typ 2 zukommt, sind bis heute nicht vollständig aufgeklärt. Bekannt ist jedoch, dass die zelluläre Insulinresistenz u. a. mit einer vermehrten Phosphorylierung des Insulinrezeptorsubstrates-1 (IRS-1) an mehreren Serinen und Threoninen einhergeht. IRS-1 wird nach Stimulation mit dem Phorbolester 12-OTetradecanoylphorbol-13-acetat (TPA) bzw. Insulin an der kürzlich identifizierten Serinstelle 318 phosphoryliert. Der genaue Signalweg, der zu dieser Phosphorylierung führt, ist bislang nicht bekannt. In der vorliegenden Arbeit galt es daher zu untersuchen, ob Kinasen, für die beschrieben ist, dass sie IRS-1 phosphorylieren können, an dieser TPA- bzw. Insulin-induzierten Phosphorylierung beteiligt sind. Die Phosphorylierung von IRS-1 an Serin 318 wurde in C2C12-Myotuben mittels Western-Blotting nachgewiesen. Die 30-minütige Stimulation mit TPA führte zu einer starken Phosphorylierung von IRS-1 an Serin 318. Durch 30-minütige Vorinkubation mit dem PKCInhibitor Bisindolylmaleimid I (500 nM), konnte die Phosphorylierung nach 30-minütiger Stimulation mit 100 nM TPA deutlich abgeschwächt und die Phosphorylierung nach 30-minütiger Stimulation mit 1 und 10 nM TPA auf das basale Niveau reduziert werden. Die Stimulation mit 100 nM Insulin (30 min) führte ebenfalls zu einer starken Phosphorylierung von IRS-1 an Serin 318. Die Vorinkubation mit dem Inhibitor der c-Jun-N-terminalen Kinase (JNK) SP600125 (50 mikroM...

‣ Einfluss freier Fettsäuren auf die Insulinsekretion beim Menschen; Influence of free fatty acids on insulin secretion in humans

Steigenberger, Mirjam Elisabeth
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.553423%
Zu den pathophysiologischen Grundlagen des Diabetes mellitus Typ 2 gehören die Insulinresistenz und die gestörte Insulinsekretion. Ziel dieser Arbeit war es, zu untersuchen, ob der Spiegel der freien Fettsäuren im Nüchternplasma bei Risikopersonen für Diabetes mellitus Typ 2 die Insulinsekretion beeinträchtigt. Hierfür untersuchten wir in einer Querschnittsuntersuchung 1055 Probanden mit positiver Familienanamnese für Typ 2 Diabetes mellitus. Unabhängig von Alter, Geschlecht, Insulinsensitivität und prozentualem Fettgehalt des Körpers fanden wir in unserer multivariaten linearen Regressionsanalyse eine statistisch signifikante negative Korrelation (p<0,0001) der Konzentration nüchtern freier Fettsäuren mit der ersten Phase der Insulinsekretion. Dieser Befund bestätigt Hinweise aus früheren Studien. Aus bisher durchgeführten Studien ging jedoch nicht hervor, ob ein erhöhter Nüchternspiegel freier Fettsäuren die Entwicklung der ersten Phase der Glukose-induzierten Insulinsekretion beeinflusst oder voraussagen kann. Außerdem war bisher unklar inwiefern der Nüchternspiegel der freien Fettsäuren und die Änderung der ersten Phase der Glukose-induzierten Insulinsekretion durch eine Lebensstiländerung beeinflusst werden können. Zu diesem Zweck untersuchten wir bei 105 Probanden mit positiver Familienanamnese für Typ 2 Diabetes mellitus den Nüchternspiegel freier Fettsäuren und im Rahmen eines oralen Glukosetoleranztests die erste Phase der Insulinsekretion vor und nach einer 9-monatigen Lebensstilintervention. Außerdem wurden anthropometrische und metabolische Parameter erhoben...

‣ Auswirkungen des Gly972Arg-Polymorphismus im Insulin Rezeptor Substrat-1 (IRS-1) auf die Insulinsensitivität des zentralen Nervensystems; Effects of Gly972Arg-Polymorphism in the Insulin Receptor Substrate-1 (IRS-1) on insulin sensitivity of the central nervous system

Klösel, Benjamin
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.572888%
Die vorliegende Arbeit befasst sich mit der Frage, ob die Insulinsensitivität des zentralen Nervensystems (ZNS) von einer genetischen Komponente mitbestimmt wird. Nachdem das Gehirn eine lange Zeit als insulinunempfindliches Organ galt, zeigten neuere Studien, dass Insulinrezeptoren mit funktionsfähiger Signaltransduktionskaskade im ZNS vorhanden sind. Es konnten im weiteren Verlauf eine modulierende Wirkung von Insulin auf Energiehomöostase, Kognition, Nahrungsaufnahme und Reproduktion nachgewiesen werden. Unsere Gruppe konnte in zwei Experimenten den Nachweis erbringen, dass sich die Insulinwirkung am ZNS durch Messung der spontanen und stimulierten kortikalen Aktivität im Magnetencephalografen (MEG) beurteilen lässt, und dass der Insulineffekt bei übergewichtigen im Vergleich zu normalgewichtigen Probanden nicht vorhanden ist. Während bei diesen Experimenten das Hauptaugenmerk auf Umweltvariablen (Gewicht des Probanden, Body-mass index, Körperfett) lag, stellte sich die Frage, ob auch genetischen Variablen eine beeinflussende Rolle zukommt. Um dies zu untersuchen wählten wir Probanden mit einem prävalenten Polymorphismus im IRS-1 Gen (Gly972Arg), der zu einer Beeinträchtigung der normalen Signaltransduktion führt und somit möglicherweise Auswirkungen auf die Insulinsensitivität hat. Um etwaige Auswirkungen auf die Insulinsensitivität des ZNS beurteilen zu können...

‣ Untersuchungen zur adipogenen Wirkung von Insulin Detemir auf 3T3-L1-Präadipozyten; Investigation of adipogenic effects of insulin detemir on 3T3-L1-preadipocytes

Böhm, Anja Andrea
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.548313%
Da bis heute eine Heilung der Volkskrankheit Diabetes nicht möglich ist, bleibt die Vermeidung der Folgeschäden durch normnahe Blutglukose in Folge Imitation einer möglichst physiologischen Insulinzufuhr oberstes Ziel. Insulin Detemir mit seinem langen Wirkprofil kann dies durch die Albuminbindung, der ein Myristinsäurerest zugrunde liegt, nahezu erreichen. In vielen Studien konnte inzwischen nachgewiesen werden, dass Detemir – im Vergleich zu herkömmlichen Insulinen - keinen Gewichtsanstieg hervorruft. Aus diesem Grund wurde die Wirkung des Insulin Detemir auf das wichtige Erfolgsorgan Fettgewebe anhand der Differenzierung von 3T3-L1-Präadipozyten auf drei Ebenen untersucht, jeweils versus Humaninsulin: die enzymatische Ebene mit der photometrisch bestimmten GPDH-Aktivität als Differenzierungsmarker; die morphologische mittels mikroskopischer Ansicht nach Färbung der Fetttröpfchen, sowie die Ebene der Genexpression, da während der Adipogenese mehr als 2000 Gene in ihrer Expression verändert werden; es wurden PPARG2 und Leptin als Differenzierungsmarker mittels Polymerase-Ketten-Reaktion quantifiziert. Da sich in den ersten Experimenten eine starke Differenzierungs-hemmung durch Serumalbumin zeigte, mussten alle Versuche in Abwesenheit von Albumin stattfinden. Bei supraphysiologischen Konzentrationen trat eine signifikant höhere Adipogenität des DET auf...

‣ The Role of Insulin and Insulin Signaling in Eye Growth Regulation; Das Interesse an dem Zusammenhang zwischen Insulin und der Ausbildung von Myopie und den zugrundeliegenden molekularen Signalwegen

Marchã Penha, Maria Alexandra
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.595232%
The prevalence of myopia in the human population has dramatically increased in developed regions of Asia (Lin, 1999) but also in Western societies during the last decades (Vitale, 2009) and it is estimated that more than 30% of the worldwide population is currently myopic (Dirani, 2006). Although myopia is not a life-threatening disease, high myopia (more than 6 diopters) increases the risk of secondary diseases, such as myopic choroidal neovascularization, retinal degeneration, retinal detachment and glaucoma and thus the risk of becoming blind. It is therefore important to study the mechanisms underlying eye growth regulation. The interest in studying the role of insulin in myopia development and to investigate the underlying molecular pathways is mainly based on three different key findings. First, it was previously found that glucagon, a peptide hormone with opposite metabolic effects to those of insulin, acts as a “STOP” signal for myopia development in the chicken model of myopia (Bitzer, 2002). Two parallel studies proved that, in fact, glucagon and insulin have opposite effects on axial eye growth as well (Feldkaemper, 2009; Zhu, 2009), with insulin acting as a “GO” signal. In 2002, Cordain and collaborators stated that “during the last years diet has changed. Diets high in refined starches such as bread and cereals increase insulin levels in humans". It was further hypothesized that “high levels of insulin lead to a fall of insulin-binding protein 3 which could disturb the coordination of the eye ball lengthening and lens growth…” Second...

‣ Efeito da rosiglitazona e da lovastatina na resistencia insulinica da dieta hiperlipidica; Effects of rosiglitazone and lovastatin in insulin resistance of high-fat fed rats

Cristina Alba Lalli
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 07/12/2007 Português
Relevância na Pesquisa
36.548313%
A insulina é o principal hormônio anabólico, que atua através da ativação de transportadores, regulação de enzimas e expressão de genes que codificam enzimas envolvidas na captação e armazenamento de substratos. Para exercer suas ações, a insulina emprega duas vias principais de sinalização intracelular: a via da PI 3-quinase e a via da MAPK. A regulação da ação do hormônio se faz por meio de vários mecanismos. O modelo animal de dieta hiperlipídica apresenta alterações metabólicas e de sinalização semelhantes aos encontrados na resistência insulínica de humanos com obesidade induzida por dieta. O objetivo de nosso trabalho foi estudar em ratos alimentados com dieta hiperlipídica, etapas da sinalização insulínica e também algumas vias de regulação da sinalização, após o uso de duas drogas: a rosiglitazona, uma tiazolidinediona usada para o tratamento do diabetes melito tipo 2 como sensibilizadora de insulina e a lovastatina, droga inibidora da HMGCoA redutase, que diminui a síntese de colesterol, mas que também tem apresentado efeito de aumentar a sensibilidade à insulina, tanto em modelos animais como em humanos. Ratos alimentados com dieta hiperlipídica por quatro semanas e tratados na última semana com as drogas...