RESUMEN
We have identified a region within the beta CGRP gene which has the potential to encode a novel calcitonin-like peptide. The gene is located on the short arm of chromosome 11 (11p 12-14.2) and we suggest that it resulted from a local duplication of the alpha gene. We have been unable to detect the corresponding mRNA in a variety of tissues which express alpha-calcitonin. It is not clear whether this sequence can be expressed in man.
Asunto(s)
Calcitonina/genética , Neuropéptidos/genética , Secuencia de Bases , Péptido Relacionado con Gen de Calcitonina , Cromosomas Humanos Par 11 , ADN Recombinante , Humanos , Hibridación de Ácido NucleicoRESUMEN
We have used the polymerase chain reaction with mixed sequence primers to generate a probe for rat amylin and have used this to detect expression in various rat tissues. Amylin mRNA is found in greatest concentrations in the pancreas where a single mRNA species can be detected giving a hybridisation signal intensity approximately 10% that of insulin mRNA. When the beta cell population was depleted with streptozotocin, both amylin and insulin mRNAs were reduced to a similar extent. Consistent with its supposed role in the control of carbohydrate metabolism, amylin mRNA was also found in the stomach. Unlike the related peptide, CGRP, amylin mRNA is not present in the thyroid and is not widely distributed in the central nervous system. The only nervous tissue in which it could be detected was the dorsal root ganglion. Surprisingly, amylin mRNA was also found in the lung though only at very low levels.
Asunto(s)
Amiloide/genética , Páncreas/análisis , ARN Mensajero/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Gatos , Sistema Nervioso Central/análisis , Clonación Molecular , ADN/aislamiento & purificación , Diabetes Mellitus Experimental/genética , Sistema Digestivo/análisis , Polipéptido Amiloide de los Islotes Pancreáticos , Islotes Pancreáticos/análisis , Masculino , Datos de Secuencia Molecular , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Ratas , Ratas Endogámicas , EstreptozocinaRESUMEN
The response of the islet amyloid polypeptide gene to chronic dexamethasone treatment in adult rats was investigated. After 12 daily injections, rats were severely underweight and fasting blood glucose levels were elevated. When pancreatic mRNA was analysed, a 16-fold elevation in islet amyloid polypeptide mRNA was observed with only a four-fold increase in insulin mRNA levels. Pancreatic islet amyloid polypeptide and insulin mRNA levels were also determined 12 days after streptozotocin treatment. In these rats, which were not severely diabetic, the reduction in islet amyloid polypeptide mRNA levels was sixfold less than the reduction in insulin mRNA levels. In both these models of diabetes the ratio of islet amyloid polypeptide to insulin mRNA levels was raised. This would not be expected if the physiological role of islet amyloid polypeptide is as a simple hyperglycaemic agent opposing insulin action or release.