RESUMEN
The morphological and biochemical changes that occur in the early phase of streptozotocin (STZ)-induced beta cell failure have not been characterized. The pancreas and plasma of rats treated with STZ were processed for morphological and biochemical parameters 1-24 h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3 h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1 h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24 h after STZ treatment. The number of insulin-positive cells decreased significantly (p<0.05) at 24 h after STZ treatment with a concomitant increase in the number of glucagon-immunoreactive cells. Electron microscopy showed coalescing of beta cell granules 18 h after STZ treatment. A near to complete degranulation of beta cells settled at 21 h after STZ administration. The pancreatic tissue and plasma levels of adrenaline and noradrenaline increased significantly (p<0.004: pancreatic tissue; p<0.04: plasma) 3 h after STZ treatment and remained high after a reduction at 6 h post STZ treatment. The pancreatic tissue and plasma levels of 5-HIAA decreased significantly (p<0.002 pancreatic tissue; p<0.04: plasma) 1 h after STZ treatment and remained low after a reduction at 6-9 h post STZ treatment. STZ elicited significant dose-dependent increases in insulin secretion from the isolated pancreas. The early changes in catecholamine level may be used in screening and follow-up studies on diabetes mellitus.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/ultraestructura , Estreptozocina/toxicidad , Animales , Degranulación de la Célula/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Epinefrina/sangre , Glucagón/sangre , Glucagón/metabolismo , Ácido Hidroxiindolacético/sangre , Ácido Hidroxiindolacético/metabolismo , Hiperglucemia/inducido químicamente , Técnicas In Vitro , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/fisiología , Masculino , Norepinefrina/sangre , Concentración Osmolar , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Ratas , Ratas Wistar , Vesículas Secretoras/efectos de los fármacos , Vesículas Secretoras/metabolismo , Vesículas Secretoras/ultraestructura , Factores de Tiempo , Pérdida de Peso/efectos de los fármacosRESUMEN
Ventricular electrical conduction has been investigated in the streptozotocin (STZ)-induced diabetic rat. Diabetes was induced with a single injection of STZ (60 mg/kg bodyweight, ip). The ECG was measured continuously, in vivo, using a biotelemetry system. Left ventricular action potentials were recorded with an extracellular suction electrode. Expression of mRNA transcripts for selected ion transport proteins was measured in left ventricle with real-time RT-PCR. At 10 weeks after STZ treatment, in vivo heart rate (HR) was reduced (267 +/- 3 vs. 329 +/- 5 BPM), QRS complex duration and QT interval were prolonged in diabetic rats compared to controls. In vitro spontaneous HR was reduced and paced heart action potential repolarization was prolonged in diabetic rats compared to controls. The mRNA expression for Kcnd2 (I (to) channel) and Kcne2 (I (kr) channel) was significantly reduced in diabetic rats compared to controls. Altered gene expression and, in particular, genes that encode K(+) channel proteins may underlie delayed propagation of electrical activity in the ventricular myocardium of STZ-induced diabetic rat.
Asunto(s)
Potenciales de Acción , Diabetes Mellitus Experimental/fisiopatología , Regulación de la Expresión Génica , Ventrículos Cardíacos/fisiopatología , Canales de Potasio con Entrada de Voltaje/genética , Canales de Potasio Shal/genética , Animales , Electrocardiografía , Frecuencia Cardíaca , Miocardio/metabolismo , ARN Mensajero/análisis , RatasRESUMEN
Orexin-B, ghrelin and their receptors play an important role in the regulation of feeding in mammals. The pattern of distribution of orexin-B, orexin-1-receptor (OX1R), ghrelin and growth hormone secretagogue receptor (GHS-R) in the lacrimal gland of normal and diabetic rats has not been reported. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg kg(-1). Forty weeks after the induction of STZ-induced diabetes, normal, age-matched controls and diabetic rats were anesthetized with chloral hydrate (intraperitoneally) and their lacrimal glands removed and processed for immunofluorescence. Orexin-B was observed in the cells localized to the interacinar regions while OX1R was discerned in the nerves innervating the wall of small blood vessels. Ghrelin was also present in a group of cells located in the periacinar regions of the lacrimal glands of normal and diabetic rats. In contrast, GHS-R was observed in the apical region of the ductal cells of the lacrimal glands of both normal and diabetic rats. The pattern of distribution of these orexigenic peptides and their receptors did not significantly change after the onset of diabetes. In conclusion, orexin-B, ghrelin and their receptors are present in the lacrimal glands of both normal and diabetic rats and may play a role in the regulation of lacrimal gland function.
