Beneficial effects of immunotherapy with extracts derived from Actinomycetales on rats with spontaneous obesity and diabetes.

AIMS: To determine whether immunotherapy with heat-killed, selected Actinomycetales species could influence the progression of spontaneous Type 2 diabetes mellitus and obesity in a rat model. MATERIALS & METHODS: Preparations of either Gordonia bronchialis, Tsukamurella inchonensis or a saline placebo were given by three subcutaneous injections, 30 days apart, starting when rats were aged 120 days, just before development of Type 2 diabetes mellitus, and at day 440, when the disease was well established. Bodyweight, blood sugar, cholesterol, triglycerides and insulin levels were measured to determine the effects and at the end of the experiments, animals were subjected to necropsy. RESULTS: The development of Type 2 diabetes mellitus was prevented by both reagents, most effectively by T. inchonensis. In the treatment experiment, the effects of the disease were reduced by both treatments, markedly so by T. inchonensis. In both experiments obesity was reduced in treated animals. The possible mechanisms of action are discussed. CONCLUSION: Our findings suggest that Type 2 diabetes mellitus in the studied rats is associated with obesity, and that both diabetes and obesity can be prevented or improved by treatment with Actinomycetales immune modulators.

[Dynamic modifications in islets of Langerhans in two lines of spontaneously diabetic rats]. / Modificaciones dinámicas en los islotes de Langerhans de dos lineas de ratas espontáneamente diabéticas.

The eSMT rat is derived from the crossing of eSS and beta, both lines belonging to the IIM strain, while eSS is a model of type 2 diabetes without overweight and beta develops moderate obesity and late glucose intolerance. Metabolic characteristics and histopathological findings in endocrine pancreas of eSS and eSMT were compared. Young eSMT animals are more robust than eSS and develop more intense fasting hyperglycemia and glucose intolerance at an earlier age. eSMT males of 6 and 9 months show islets with altered shapes and fibrosis, as well as sporadic images of apoptosis. At 12 months of age, islets are reduced in number and size, resembling the histoarchitecture of eSS males during their second year of life; eventually islets undergo disruption and, at the same time, occasional mitoses and nesidioblastosis are seen. These dynamic modifications may be expressing a response to hyperglycemia. eSS females preserve their insular structure for a longer time and have less glycemic alterations. Sexual dimorphism of the diabetic syndrome of eSMT is attenuated when compared with eSS. The construction of a typology of individuals through multivariate analysis separated three clusters, evidencing genetic, age and sex differences.

Modificaciones dinámicas en los islotes de Langerhans de dos Líneas de ratas espontaneamente diabeticas / Dynamic modifications in islets of Langerhans in two lines of spontaneously diabetic rats

La rata eSMT derivó del cruzamiento de eSS y b, líneas de la cepa IIM. eSS es un modelo de diabetes tipo 2 sin sobrepeso; b desarrolla obesidad moderada e intolerancia tardía a la glucosa. Fueron comparados características metabólicas y hallazgos histopatológicos del páncreas endocrino entre eSS y eSMT. Cotejados con eSS, los animales eSMT jóvenes son más corpulentos y desarrollan hiperglucemia de ayuno e intolerancia a la glucosa más precoces e intensas. En los machos eSMT de 6 y 9 meses existen islotes de formas alteradas y con fibrosis, detectándose esporádicas imágenes de apoptosis. En los de un año se tornan más pequeños y escasos, remedando la histoarquitectura de los machos eSS en el segundo año de vida; posteriormente los islotes van disgregándose, a la vez que muestran ocasionales mitosis y se observa nesidioblastosis. Se sugiere que estas modificaciones dinámicas constituyen una respuesta a la hiperglucemia. Las hembras eSS conservan por más tiempo la estructura insular y tienen menores alteraciones de la glucemia. El dimorfismo sexual del síndrome diabético de eSMT es atenuado respecto de eSS. La construcción de una tipología de individuos mediante el análisis multivariado separó tres clusters, evidenciando diferencias genéticas, etáreas y de sexo.

The eSMT rat is derived from the crossing of eSS and b, both lines belonging to the IIM strain, while eSS is a model of type 2 diabetes without overweight and b develops moderate obesity and late glucose intolerance. Metabolic characteristics and histopathological findings in endocrine pancreas of eSS and eSMT were compared. Young eSMT animals are more robust than eSS and develop more intense fasting hyperglycemia and glucose intolerance at an earlier age. eSMT males of 6 and 9 months show islets with altered shapes and fibrosis, as well as sporadic images of apoptosis. At 12 months of age, islets are reduced in number and size, resembling the histoarchitecture of eSS males during their second year of life; eventually islets undergo disruption and, at the same time, occasional mitoses and nesidioblastosis are seen. These dynamic modifications may be expressing a response to hyperglycemia. eSS females preserve their insular structure for a longer time and have less glycemic alterations. Sexual dimorphism of the diabetic syndrome of eSMT is attenuated when compared with eSS. The construction of a typology of individuals through multivariate analysis separated three clusters, evidencing genetic, age and sex differences.

Modificaciones dinámicas en los islotes de Langerhans de dos Líneas de ratas espontaneamente diabeticas / Dynamic modifications in islets of Langerhans in two lines of spontaneously diabetic rats

La rata eSMT derivó del cruzamiento de eSS y b, líneas de la cepa IIM. eSS es un modelo de diabetes tipo 2 sin sobrepeso; b desarrolla obesidad moderada e intolerancia tardía a la glucosa. Fueron comparados características metabólicas y hallazgos histopatológicos del páncreas endocrino entre eSS y eSMT. Cotejados con eSS, los animales eSMT jóvenes son más corpulentos y desarrollan hiperglucemia de ayuno e intolerancia a la glucosa más precoces e intensas. En los machos eSMT de 6 y 9 meses existen islotes de formas alteradas y con fibrosis, detectándose esporádicas imágenes de apoptosis. En los de un año se tornan más pequeños y escasos, remedando la histoarquitectura de los machos eSS en el segundo año de vida; posteriormente los islotes van disgregándose, a la vez que muestran ocasionales mitosis y se observa nesidioblastosis. Se sugiere que estas modificaciones dinámicas constituyen una respuesta a la hiperglucemia. Las hembras eSS conservan por más tiempo la estructura insular y tienen menores alteraciones de la glucemia. El dimorfismo sexual del síndrome diabético de eSMT es atenuado respecto de eSS. La construcción de una tipología de individuos mediante el análisis multivariado separó tres clusters, evidenciando diferencias genéticas, etáreas y de sexo.(AU)

The eSMT rat is derived from the crossing of eSS and b, both lines belonging to the IIM strain, while eSS is a model of type 2 diabetes without overweight and b develops moderate obesity and late glucose intolerance. Metabolic characteristics and histopathological findings in endocrine pancreas of eSS and eSMT were compared. Young eSMT animals are more robust than eSS and develop more intense fasting hyperglycemia and glucose intolerance at an earlier age. eSMT males of 6 and 9 months show islets with altered shapes and fibrosis, as well as sporadic images of apoptosis. At 12 months of age, islets are reduced in number and size, resembling the histoarchitecture of eSS males during their second year of life; eventually islets undergo disruption and, at the same time, occasional mitoses and nesidioblastosis are seen. These dynamic modifications may be expressing a response to hyperglycemia. eSS females preserve their insular structure for a longer time and have less glycemic alterations. Sexual dimorphism of the diabetic syndrome of eSMT is attenuated when compared with eSS. The construction of a typology of individuals through multivariate analysis separated three clusters, evidencing genetic, age and sex differences.(AU)

Conducta alimentaria y perfil glucémico en dos líneas de ratas con diabetes genética: eSS y eSMT / Feeding behavior and glycemic profile in two lines of rats with genetic diabetes

Introducción. La alimentación puede agravar la diabetes de humanos y modelos animales. Entre ellos, la rata eSMT presenta un curso más exacerbado y mayor biomasa que la línea parental eSS. Objetivo. Estudiar la conducta alimentaria de ratas macho eSMT y eSS ante oferta ilimitada y bajo restricción alternada, analizando su incidencia sobre el peso y la glucemia. Materiales y métodos. Se registró el consumo ad libitum en etapas de crecimiento y mantenimiento. Un grupo de eSMT recibió durante 5 semanas a partir del destete, una dietarestringida intermitente seguida de oferta ilimitada, y otro fue restringido hasta el año de edad, midiéndose el peso y el perfil glucémico en distintas edades. Resultados. Durante el crecimiento, eSMT aumentó de peso más que eSS con ingestas similares, y en la etapa de mantenimiento sustentó mayor biomasa con menor consumo. Larestricción intermitente posterior al destete indujo un patrón de crecimiento más lento y menor peso adulto. A los 5 meses presentaron valores de G0 normales (85±12 mg/dl) y los controles mostraron cifras alteradas (119±14 mg/dl). En los animales restringidos la posterior oferta ilimitada produjo glucemias de ayuno compatibles con diabetes (163±25 mg/dl) y un incremento ponderado 75 por ciento superior a los alimentados ad libitum. Conclusión. La alternancia prolongada hambre-saciedad indujo en eSMT desaceleración de su metabolopatía mientras que la realimentación se asoció con incrementos superiores de peso y glucemia, atribuibles a un aumento de la eficiencia de conversión inducida por el ayuno. Estos resultados enfatizan la importancia de mejorar el conocimiento sobre las relaciones entre crecimiento, alimentación y diabetes

[Feeding behavior and glycemic profile in two lines of rats with genetic diabetes]. / Conducta alimentaria y perfil glucémico en dos líneas de ratas con diabetes genética: eSS y eSMT.

INTRODUCTION: Food intake can aggravate diabetes in humans and in animal models. In rat model systems, the eSMT rat strain shows increased diabetes expression and higher biomass than its eSS parental line. OBVJECTIVE: The feeding behavior of eSMT and eSS males was compared under conditions of ad libitum versus restrictive food intake. The effects on rat weight and glycemia were examined. MATERIALS AND METHODS: Unrestricted food intake during growth and maintenance stages was recorded. One group of eSMT was submitted to intermittent dietary restriction for 5 weeks after weaning, followed by ad libitum food availability. A second group was restricted until one year of age. Weights and glycemic profiles were measured at periodic intervals. RESULTS: During the growth stage, eSMT showed weight increases higher than the eSS with similar food intake. In the maintenance stage, eSMT reached higher biomass with less intake. Post-weaning alternate restriction induced a slower growth pattern and lower adult weight. After five months of fasting, glycemia was normal (85 +/- 12 mg/dl) and controls showed altered values (119 +/- 14 mg/dl). Ad libitum nutrition after restriction resulted in glycemia levels compatible with diabetes (163 +/- 25 mg/dl) and a weight gain 75% higher than in ad libitum-fed animals. CONCLUSIONS: Prolonged hunger-satiety alternation induced slowing of the eSMT metabolopathy, whereas refeeding was associated with higher increases of weight and glycemia. This was imputed to an augmented conversion efficiency caused by fasting. These results emphasize the importance of understanding the relations between growth, feeding and diabetes.

[Chronic bronchial dilatations in different colonies of laboratory rats]. / Dilataciones bronquiales crónicas en differentes colonias de ratas de laboratorio.

Bronchiectasis occurred naturally in 12-month-old spontaneously diabetic eSS male rats. The lungs of 3 and 6-month-old eSS rats were compared in eumetabolic eSS rats from three inbred lines consisting of inbred spontaneously diabetic eSS derived from IIM strain; these were compared with eumetabolic, outbred Wistar rats, paired by sex and age. Acrylic casts of bronchial tree were obtained after injection of a plastic substance. The casts were pruned to focus on the first four bronchial branchings. Diameter and volume of the conductive bronchial tree were determined using a binocular magnifier. Histological sections were obtained. All lines showed multiple bronchiectasis, mostly fusiform, bronchial dilatation and inflammatory response with lymphocytic infiltrates. These symptoms were much more severe in 180-day-old eSS males. Bacteria were isolated from the lungs in 70% of cases (n = 32), except in eSS rats. Pseudomonas spp. (38%) and Gram-positive cocci as coagulase-negative Staphylococcus spp. (20%) were detected. Neither pathogenic bacteria nor saprophyte fungi were found. Although all lines were affected, diabetes in eSS appears to be an aggravating factor.

Dilataciones bronquiales crónicas en diferentes colonias de ratas de laboratorio / Bronchial chronic dilatations in different colonies of laboratory rats

Ante la aparición espontánea de bronquiectasias en ratas macho eSS diabéticas, se examinaron los pulmones de ratas eSS de 3 a 6 meses de edad y los de ratas eumetabólica de tres líneas: eSS endocriada con diabetes espontánea tipo 2 derevida de la cepa IIM; líneas e, m y alfa endocriadas, y Wistar eumetabólica y exocriada, agrupadas según sexo y edad. Se obtuvieron moldes se recortaron y se concentró la observación en las primeras cuatro ramificaciones bronquiales; se determinaron el diámetro y el volumen con la lente binocular de aumento. Además, se obtuvieron cortes histológicos. Aunque en todas las líneas se observaron bronquiectasias múltiples, principalmente fusiformes, la dilatación bronquial y la respuesta inflamatoria con los infiltrados linfocíticos fueron mucho más graves en los machoos eSS de 180 días de edad. En el 70 por ciento de los casos (n=32) se aislaron bacterias en los pulmones, excepto en las ratas eSS. Se detectaron Pseudomona spp. (38 por ciento) y cocos Gram positivos en forma de Staphylococcus spp. coagulasa negativos (20 por ciento). No se encontraton hongos patógenos ni saprofíticos. Si bien todas las líneas aparecen afectadas, la diabetes de eSS sería un factor agravante