RESUMO
Recent studies have implicated pre-beta and beta lipoproteins (VLDL and LDL) in the etiopathogenesis of complications of diabetes mellitus (DM). In contrast, alpha lipoprotein (HDL) is protective of the beta cells of the pancreas. This study examined the distribution of HDL in the islets of Langerhans of murine models of type 1 diabetic rats (streptozotocin (STZ)-induced DM in Wistar rats) and type 2 models of DM rats (Goto-Kakizaki (GK), non-diabetic Zucker lean (ZL), and Zucker diabetic and fatty (ZDF)). The extent by which HDL co-localizes with insulin or glucagon in the islets of the pancreas was also investigated. Pancreatic tissues of Wistar non-diabetic, diabetic Wistar, GK, ZL, and ZDF rats were processed for immunohistochemistry. Pancreatic samples of GK rats fed with either a low-fat or a high-fat diet were prepared for transmission immune-electron microscopy (TIEM) to establish the cytoplasmic localization of HDL in islet cells. HDL was detected in the core and periphery of pancreatic islets of Wistar non-diabetic and diabetic, GK, ZL, and ZDF rats. The average total of islet cells immune positive for HDL was markedly (<0.05) reduced in GK and ZDF rats in comparison to Wistar controls. The number of islet cells containing HDL was also remarkably (p < 0.05) reduced in Wistar diabetic rats and GK models fed on high-fat food. The co-localization study using immunofluorescence and TIEM techniques showed that HDL is detected alongside insulin within the secretory granules of ß-cells. HDL did not co-localize with glucagon. This observation implies that HDL may contribute to the metabolism of insulin.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ilhotas Pancreáticas , Ratos , Camundongos , Animais , Insulina/metabolismo , Glucagon/metabolismo , Diabetes Mellitus Experimental/metabolismo , Roedores , Lipoproteínas HDL/metabolismo , Ratos Wistar , Ratos Zucker , Ilhotas Pancreáticas/metabolismo , Hormônios Pancreáticos/metabolismo , Diabetes Mellitus Tipo 2/metabolismoRESUMO
Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24-51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10-6M and 10-12M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.
Assuntos
Diabetes Mellitus Experimental/sangue , Grelina/farmacologia , Insulina/sangue , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Jejum/sangue , Teste de Tolerância a Glucose , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/ultraestrutura , Masculino , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
INTRODUCTION: Early life exposures, particularly environmental and parental lifestyle factors, have a major influence on children's health and development. Due to increasing interest in the early life developmental origins of diseases, many birth cohorts have been established. These studies constitute a repository of data which researchers use over many years to investigate emerging research questions. However, no such databank or cohort study is available in the United Arab Emirates (UAE). This project aims to establish a prospective mother and child cohort study in Al Ain (Abu Dhabi, UAE) to investigate the maternal and early life determinants of infant, child, adolescent and maternal health of the Emirati population. METHODS AND ANALYSIS: During the period 2017-2021, this study aims to recruit 10 000 pregnancies at approximately 12 weeks of gestation from hospitals and clinics in Al Ain city. For each mother/newborn pair, an initial dataset will be collected including anthropometric, physiological and biochemical measurements, medical interventions, circumstances of pregnancy, delivery details and neonatal and perinatal growth and health using a combination of questionnaires, interviews and medical record extractions. Baseline data will act as the starting point from which the children will be followed up and re-surveyed at intervals throughout their life course until the age of 16 years, to explore how familial, socioeconomic and lifestyle factors interact with genetic and environmental factors to influence health outcomes and achievements later in life. ETHICS AND DISSEMINATION: Ethical approval has been granted by the United Arab Emirates University Human Research Ethics Committee and the ethical committees of the participating institutions. Results will be widely disseminated via peer-reviewed manuscripts, conference presentations, media outlets and reports to relevant authorities.