Assuntos
Glicemia , Insulina/administração & dosagem , Nebulizadores e Vaporizadores , Administração por Inalação , Animais , Área Sob a Curva , Glicemia/análise , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Injeções Subcutâneas , Insulina/farmacocinética , Pulmão/efeitos dos fármacos , Pulmão/ultraestrutura , Macaca mulatta , MasculinoRESUMO
Recent data suggest that proinsulin is strongly associated with cardiovascular risk factors in diabetic subjects. However, this relationship has not been examined in nondiabetic subjects. Therefore, we examined the relation of proinsulin to lipids, obesity (body mass index), and waist-to-hip ratio in 260 nondiabetic individuals from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Proinsulin was measured by radioimmunoassay, and insulin was measured by a Linco radioimmunoassay that does not cross-react with proinsulin. Fasting insulin was significantly associated with body mass index (0.42), waist-to-hip ratio (r = 0.30), triglyceride (r = 0.29), high-density lipoprotein cholesterol (r = -0.20), and systolic blood pressure (r = 0.16) but not significantly related to diastolic blood pressure (r = 0.11). Fasting proinsulin was significantly associated with body mass index (r = 0.19), waist-to-hip ratio (r = 0.25), triglyceride (r = 0.41), systolic blood pressure (r = 0.19), and diastolic blood pressure (r = 0.15). Proinsulin was more strongly related to increased triglyceride than insulin despite its weaker relationship to obesity. In multivariate analyses, proinsulin continued to be significantly related to triglyceride concentrations (explaining 23.1% of the variance) and to systolic blood pressure (explaining 4.0% of the variance), even after adjusting for insulin. These observations suggest that proinsulin should be measured in addition to insulin in epidemiological studies. Proinsulin may be a marker for metabolic decompensation in prediabetic subjects.
Assuntos
Doenças Cardiovasculares/etiologia , Insulina/sangue , Proinsulina/sangue , Adulto , Antropometria , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Hemodinâmica , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Texas/epidemiologiaRESUMO
To model islet amyloidogenesis in NIDDM and explore the glucoregulatory role of islet amyloid polypeptide (IAPP), we have created transgenic mice containing a rat insulin-I promoter-human IAPP fusion gene. Expression of human IAPP was localized to the islets of Langerhans, anterior pituitary and brain in transgenic animals; blood IAPP levels were elevated 5-fold while fasting glucose levels remained normal. Amyloid deposits have not been detected in transgenic islets suggesting that other co-existing abnormalities in NIDDM may be required for the formation of islet amyloid. These animals provide a unique model for exploring this hypothesis and other proposed functions of IAPP.
