RESUMO
BACKGROUND: Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model. METHODS: Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals. KEY RESULTS: We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1ß concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1ß reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls. CONCLUSIONS: The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Trânsito Gastrointestinal , Resistência à Insulina , Intestino Delgado/fisiopatologia , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Duodeno/inervação , Duodeno/metabolismo , Duodeno/fisiopatologia , Íleo/inervação , Íleo/metabolismo , Íleo/fisiopatologia , Mediadores da Inflamação/metabolismo , Intestino Delgado/inervação , Intestino Delgado/metabolismo , Jejuno/inervação , Jejuno/metabolismo , Jejuno/fisiopatologia , Masculino , Plexo Mientérico/fisiopatologia , Ratos Wistar , Plexo Submucoso/fisiopatologiaRESUMO
OBJECTIVE: The posterior vagus nerve trunk innervates the entire small intestine, and elucidating its modulatory role in the IgA response was the aim of this study. METHODS: Two groups of six male BALB/c mice underwent sham or posterior subdiaphragmatic vagotomy and were euthanized on the 14th postoperative day; then, the small intestines were dissected. The intestinal fluid was harvested for antibody analysis by ELISA, and cell suspensions from Peyer's patches and lamina propria were prepared for cytofluorometric analysis of plasma cells and T lymphocytes. The CD4+ T cells were labeled for the intracellular IgA-producing interleukins (ILs)-4, -5, -6, and -10; transforming growth factor (TGF)-ß; and the inflammatory cytokines tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-12. In the intestinal tissue samples, myeloperoxidase (MPO) visualization and the enzymatic activity were assessed by immunohistochemistry and ELISA, respectively. The data were analyzed by Student's t test, and the differences were considered significant at p < 0.05. RESULTS: In the vagotomy group, the IgA levels and the CD4+ T cells labeled with mediators that promote IgA secretion, including IL-4 (only at lamina propria), TNF-α, and IFN-γ, were decreased, whereas the lamina propria IgA+ plasma cells and MPO presence/activity were increased; changes in the IgM levels, IgM+ plasma cells, and CD4+ T cells labeled with TGF-ß, which have a role in class switch recombination, were not observed. CONCLUSION: The downmodulating impact of vagotomy on IgA levels may result from defective IgA secretion without affecting class switch recombination, whereas vagotomy evoked a proinflammatory response regarding MPO. These findings may reflect the role of the vagus nerve on the control of the IgA response in the small intestine.
Assuntos
Imunidade nas Mucosas/imunologia , Imunoglobulina A/imunologia , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Nervo Vago/fisiologia , Animais , Linfócitos T CD4-Positivos/imunologia , Regulação para Baixo , Mucosa Intestinal/inervação , Intestino Delgado/inervação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plasmócitos/imunologia , VagotomiaRESUMO
BACKGROUND: The prevalence of obesity has increased at alarming rates, particularly because of the increased consumption of high-fat diets (HFDs). The influence of HFDs on intrinsic innervation and the intestinal wall has not been fully characterized. The aim of this study was to investigate the morpho-quantitative aspects of myenteric neurons and the wall of the small intestine in mice fed a HFD. METHODS: Swiss mice were fed a HFD (59% kcal from fat) or standard chow (9% Kcal from fat) for 8 weeks. Segments of the duodenum, jejunum, and ileum were subjected to histological processing for morpho-quantitative examination of the intestinal wall and mucosal cells, and immunohistochemistry was performed to evaluate myenteric neurons. The data for each segment were compared between the groups using an unpaired Student's t-test or an equivalent nonparametric test. RESULTS: The HFD increased body weight and visceral fat and decreased the length of the small intestine and the circumference of the ileum. In the duodenum, the HFD increased the density of the nitrergic subpopulation and decreased the area of nitrergic neurons and vasoactive intestinal peptide (VIP) varicosities. In the jejunum, the density of the nitrergic subpopulation was increased and the neuronal areas of the general population, nitrergic subpopulation and (VIP) varicosities were reduced. In the ileum, the density of the general population and nitrergic subpopulation were increased and the neuronal areas of the general population, nitrergic subpopulation and (VIP) varicosities were reduced. The morphometric parameters of the villi, crypts, muscular layer and total wall generally increased in the duodenum and jejunum and decreased in the ileum. In the duodenum and jejunum, the HFD promoted a decreased in the proportion of intraepithelial lymphocytes. In the ileum, the proportion of intraepithelial lymphocytes and goblet cells reduced, and the enteroendocrine cells increased. CONCLUSIONS: The high-fat diet induces changes in the myenteric innervation of the small intestine, intestinal wall and mucosal cells responsible for the secretion of hormones and maintenance of the protective intestinal barrier. The morpho-quantitative data provide a basis for further studies to clarify the influence of HFD in the motility, digestive and absorptive capacity, and intestinal barrier.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Mucosa Intestinal/patologia , Intestino Delgado/inervação , Intestino Delgado/patologia , Neurônios/química , Neurônios/patologia , Animais , Proliferação de Células , Duodeno/inervação , Duodeno/patologia , Duodeno/fisiopatologia , Células Enteroendócrinas , Células Caliciformes , Íleo/inervação , Íleo/patologia , Íleo/fisiopatologia , Mucosa Intestinal/fisiopatologia , Intestino Delgado/fisiopatologia , Jejuno/inervação , Jejuno/patologia , Jejuno/fisiopatologia , Contagem de Linfócitos , Masculino , Camundongos , Plexo Mientérico/patologia , Miosina Tipo V/análise , Neurônios Nitrérgicos/patologia , Obesidade/etiologia , Obesidade/patologia , Peptídeo Intestinal Vasoativo/análiseRESUMO
The nervous and endocrine systems jointly control intestinal movements, secretions of their glands and also participate of the processes of nutrient digestion and absorption. Therefore, the central objective of this study was to verify the existence of a possible relationship between the number of nervous cells and ganglia of the submucosal and myenteric plexuses and the number of endocrine cells in the small intestine of adult D. aurita. The utilized staining techniques were Grimelius, modified Masson-Fontana, direct immunoperoxidase and H-E. Argyrophillic, argentaffin and insulin immunoreactive endocrine cells do not numerically vary between the initial, mid and final regions of the duodenum, jejunum and ileum (P>0.05), except for argyrophillic cells in the jejunum (P>0.05). No numerical relationship has yet been verified between the number of nerve ganglia and endocrine cells, and also between nervous and endocrine cells. We recommended the use of new immunohistochemical techniques to confirm the numerical correlation between the nervous and endocrine systems in the small intestine. The morphology and distribution of endocrine cells and the nerve ganglia studied were similar to those encountered in eutherian mammals.
Assuntos
Células Enteroendócrinas/citologia , Gânglios/anatomia & histologia , Gânglios/citologia , Intestino Delgado/citologia , Intestino Delgado/inervação , Modelos Animais , Plexo Mientérico/citologia , Animais , Didelphis , Feminino , MasculinoRESUMO
This report aims to study architectural Auerbach plexus structure with NADH histochemistry (nicotinamide adenine dinucleotide, reduced form), along ages and their modifications with restricted diet in obese beta line rats. Experimental groups were: 1) After weaning, male rats were fed ad libitum (ALD) with standard rat chow. Autopsies were done at 2, 4, 8, 12, and 18 months old. 2) After weaning, one group was fed ad libitum, another group of rats were maintained on a restricted diet (RD). Autopsy was performed at 8 months of age. 3) After weaning, male rats were fed ad libitum (ALD) with standard rat chow. At 60 days old one group was continued with standard rat chow. Another group was fed with a restricted diet (RD). Autopsy was performed at 120 days old. After autopsy, segments of small intestine, proximal and distal colon were processed for NADH histochemistry. 1) At 2 months of age some empty spaces ("neuronal ghosts") were seen between neurons. Later on partial to total disruption of reticular structures was seen along ages. 2) In RD rats of 8 months of age, a mesh-like structure similar to normal control rats was observed. In ALD rats, partial to total disruption of mesh-like structures was seen. 3) In RD rats of 4 months of age, disruption intermingled with normal mesh-like zones was seen, more severe in ALD rats. Changes in Auerbach plexus structure (disruption of mesh-like appearance) in this line of rats were quite different from normal control rats suggesting dismetabolism effects. Dietary restriction delayed alterations in Auerbach plexus structures in obese rats.
Assuntos
Dieta Redutora , Intestino Delgado/inervação , Plexo Mientérico/patologia , NAD/análise , Obesidade/patologia , Animais , Histocitoquímica , Intestino Delgado/enzimologia , Intestino Delgado/patologia , Masculino , Plexo Mientérico/enzimologia , Obesidade/enzimologia , Ratos , Fatores de TempoRESUMO
The enteric nervous system comprises two major systems: the submucosal and the myenteric plexus. The aim of this study was to describe the myenteric plexus from three strains of spontaneous diabetic rats from the histological point of view. Samples of small intestine and of proximal and distal colon were obtained fom three spontaneous diabetic rats i.e., eSS, eSMT, beta strains and 1-year old Wistar rats. Specimens were stained with NADH (beta-nicotinamide adenine dinucleotide, reduced form) histochemical technique and examined with light microscope. Microscopically little modifications in mesh-like structure of intestinal Auerbach's plexus from eSS were detected in comparison with Wistar rats samples. Intestinal plexus of eSMT and beta rats showed disruption of mesh-like structures, modifications in the slightly colored background (smooth muscle) and augmented vascularization. Small intestine and colon are affected. In short: In our spontaneously diabetic rat models, mesh-like structure of Auerbach's plexus is strain dependent.
Assuntos
Diabetes Mellitus Experimental/patologia , Plexo Mientérico/ultraestrutura , Animais , Colo/inervação , Colo/patologia , Diabetes Mellitus Experimental/metabolismo , Histocitoquímica/métodos , Intestino Delgado/inervação , Intestino Delgado/patologia , Masculino , Microscopia Eletrônica de Varredura , Músculo Liso/inervação , NAD , Ratos , Ratos Endogâmicos , Ratos Wistar , Coloração e RotulagemRESUMO
The enteric nervous system comprises two major systems: the submucosal and the myenteric plexus. Theaim of this study was to describe the myenteric plexusfrom three strains of spontaneous diabetic rats from thehistological point of view. Samples of small intestineand of proximal and distal colon were obtained fromthree spontaneous diabetic rats i.e., eSS, eSMT, βstrains and 1-year old Wistar rats. Specimens werestained with NADH (β-nicotinamide adenine dinucleotide,reduced form) histochemical technique andexamined with light microscope. Microscopically little modifications in mesh-like structure of intestinal Auerbachs plexus from eSS were detected in comparisonwith Wistar rats samples. Intestinal plexus of eSMT and β rats showed disruption of mesh-like structures, modifications in the slightly colored background (smooth muscle) and augmented vascularization. Small intestine and colon are affected. In short: In our spontaneously diabetic rat models, mesh-like structure of Auerbachs plexus is strain dependent.
El sistema nerviso entérico comprende dos sistemas mayores: el plexo submucoso y el plexo mientérico. Este estudio describe la estructura histológica del plexo mientérico en tres líneas de ratas espontáneamente diabéticas. Especímenes de intestino delgado, colon proximal y colon distal fueron obtenidos de tres líneas de ratas espontáneamente diabéticas: eSS, eSMT, β y Wistar de 1 año de edad. Los materiales obtenidos fueron procesados con la técnica histoquímica del NADH (β-nicotinamida adenina dinucleotido, forma reducida) y observados en un microscopio óptico. Pequeñas modificaciones histológicas en la estructura reticular del plexo de Auerbach intestinal pueden ser detectados en las ratas eSS cuando son comparadas con las ratas Wistar. La estructura reticular del plexo de Auerbach de las ratass eSMT y β muestran una desaparición de dicha estructura reticular, disminución de la coloración de base (músculo liso) y un aumento de la vascularización. Tanto el intestino delgado como el colon están afectados. Resumiendo: en nuestros modelos experimentales de ratas diabéticas la estructura reticular del plexo de Auerbach es dependiente de la línea de rata estudiada.
Assuntos
Animais , Ratos , NAD , Diabetes Mellitus Experimental/patologia , Plexo Mientérico/ultraestrutura , Colo/inervação , Colo/patologia , Diabetes Mellitus Experimental/metabolismo , Histocitoquímica/métodos , Intestino Delgado/inervação , Intestino Delgado/patologia , Microscopia Eletrônica de Varredura , Músculo Liso/inervação , Ratos Endogâmicos , Ratos Wistar , Coloração e RotulagemRESUMO
The enteric nervous system comprises two major systems: the submucosal and the myenteric plexus. Theaim of this study was to describe the myenteric plexusfrom three strains of spontaneous diabetic rats from thehistological point of view. Samples of small intestineand of proximal and distal colon were obtained fromthree spontaneous diabetic rats i.e., eSS, eSMT, βstrains and 1-year old Wistar rats. Specimens werestained with NADH (β-nicotinamide adenine dinucleotide,reduced form) histochemical technique andexamined with light microscope. Microscopically little modifications in mesh-like structure of intestinal Auerbachãs plexus from eSS were detected in comparisonwith Wistar rats samples. Intestinal plexus of eSMT and β rats showed disruption of mesh-like structures, modifications in the slightly colored background (smooth muscle) and augmented vascularization. Small intestine and colon are affected. In short: In our spontaneously diabetic rat models, mesh-like structure of Auerbachãs plexus is strain dependent.(AU)
El sistema nerviso entérico comprende dos sistemas mayores: el plexo submucoso y el plexo mientérico. Este estudio describe la estructura histológica del plexo mientérico en tres líneas de ratas espontáneamente diabéticas. Especímenes de intestino delgado, colon proximal y colon distal fueron obtenidos de tres líneas de ratas espontáneamente diabéticas: eSS, eSMT, β y Wistar de 1 año de edad. Los materiales obtenidos fueron procesados con la técnica histoquímica del NADH (β-nicotinamida adenina dinucleotido, forma reducida) y observados en un microscopio óptico. Pequeñas modificaciones histológicas en la estructura reticular del plexo de Auerbach intestinal pueden ser detectados en las ratas eSS cuando son comparadas con las ratas Wistar. La estructura reticular del plexo de Auerbach de las ratass eSMT y β muestran una desaparición de dicha estructura reticular, disminución de la coloración de base (músculo liso) y un aumento de la vascularización. Tanto el intestino delgado como el colon están afectados. Resumiendo: en nuestros modelos experimentales de ratas diabéticas la estructura reticular del plexo de Auerbach es dependiente de la línea de rata estudiada.(AU)
Assuntos
Animais , Ratos , Plexo Mientérico/ultraestrutura , Diabetes Mellitus Experimental/patologia , NAD/análise , Colo/inervação , Colo/patologia , Diabetes Mellitus Experimental/metabolismo , Histocitoquímica/métodos , Intestino Delgado/inervação , Intestino Delgado/patologia , Microscopia Eletrônica de Varredura , Músculo Liso/inervação , Ratos Endogâmicos , Ratos Wistar , Coloração e RotulagemRESUMO
During continuous intraintestinal infusion of elementary diets, periodic fluctuation of the frequency of contractions has been observed. This study sought to characterize the temporospatial organization of this pattern and the influence of cholinergic input. Studies were performed on unanesthetized dogs with a duodenal cannula. Motor activity was recorded by means of infused catheters and external transducers. Nutrients were infused continuously at the duodenum and jejunal levels. Studies were repeated after administration of atropine. Six to 14 periodic variations of frequency of contractions during 10 basal infusion experiments were observed in random order. During duodenal infusion, atropine significantly increased the number of these events, associated with a synchronous pattern. Frequency and amplitude of contractions during jejunal infusion were significantly lower compared to duodenal infusion. Cyclic pattern elicited by nutrient infusion is related to a cholinergic mechanism; changes depend on the level of infusion.