Effects of different routes of heparin on instant blood-mediated inflammatory reaction after portal vein islet transplantation / 中南大学学报(医学版)

OBJECTIVES@#Heparin is mainly used as an anticoagulant in clinic, and it also has a certain anti-inflammatory effect. At present, after portal vein islet transplantation in diabetic patients, heparin is mainly infused through the peripheral veins of the limbs to achieve the purpose of anticoagulation and protection of the graft, rather than through the portal vein. In this study, animal experiments were conducted to investigate the effect of heparin infusion via the portal vein and marginal ear vein on the instant blood-mediated inflammatory reaction (IBMIR) after portal vein islet transplantation, which is the choice of anticoagulation methods for clinical islet transplantation to provide a basis for decision-making.@*METHODS@#A total of 50 neonatal pigs (Xeno-1 type, 3-5 days) were selected. Islets were isolated and purified from the pancreas of neonatal pigs. Ten non-diabetic Landrace pigs (1.5-2.0 months) served as recipients, and 12 000 IEQ/kg neonatal porcine islets were transplanted into the liver through the portal vein. All recipients received bolus injection of 50 U/kg of heparin 10 minutes before transplantation. After the bolus injection of heparin, the experimental group received heparin via the portal vein [10 U/(kg·h), 5 recipients], and the control group received heparin via the marginal ear vein [10 U/(kg·h), 5 recipients]. The superior vena cava blood was collected from the 2 groups pre-operation at 1, 3, 24 h post-operation of the transplantation. The portal vein blood was collected from the experimental group at 1 and 3 h after the transplantation as well. The levels of complement C3a, C5a, thrombin-antithrombin complex (TAT), β-thromboglobulin (β-TG), and D-dimer as well as activated partial thromboplastin time (APTT) in superior vena cava blood from 1 and 3 h post-transplantation were detected in the 2 groups, and the levels of anti-Xa and anti-IIa in the portal vein and superior vena cava blood from 1 and 3 h post-transplantation in the experimental group were detected. Twenty four hours after the transplantation, the liver tissues in the 2 groups were collected for pathological examination to observe the inflammatory cell infiltration and peripheral thrombosis around the islets graft in liver.@*RESULTS@#Before transplantation, there was no statistically significant difference in C3a, C5a, TAT, β-TG, D-dimer levels and APTT between the 2 groups (all P>0.05). At 1 and 3 h after transplantation, the C3a, TAT, and D-dimer levels in the experimental group were significant decreased than those in the control groups (all P<0.05), and at 3 h after transplantation the C5a was significant decreased than that in the control group (P<0.05). At 1 and 3 h after transplantation, the anti-Xa and anti-IIa levels in the portal vein blood were significantly increased than those in the superior vena cava blood in the experimental group (all P<0.05). Pathological results showed the presence of islet cell clusters in the liver blood vessels. The thrombus formation and neutrophil infiltration around islet graft was not obvious in the experimental group, while massive thrombus formation and neutrophil infiltration in the control group.@*CONCLUSIONS@#Compared with marginal ear vein infusion of heparin, the direct infusion of heparin in the portal vein has a certain inhibitory effect on complement system, coagulation system activation and inflammatory cell infiltration in portal vein islet transplantation, which may attenuate the occurrence of IBMIR.

Investigation on the mechanism of acupuncture in treatment of diabetes mellitus type 2 based on the network of islet macrophages-pancreatic adipose cells-islet β cells / 中国针灸

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.

Immunohistomorphology of pancreatic islet microvasculature and the immunophenotypic analysis of CEPC in adult diabetic rats / Inmunohistomorfología de microvasculatura de islotes pancreatic y el análisis inmunofenotípico de CEPC en ratas diabéticas adultas

SUMMARY: Hyperglycaemia is one of the main causes for the endothelial cell (EC) damage in diabetic patients. Even though circulating endothelial progenitor cells (CEPC) could be used as a prognosis for microvascular complications, there is very little information on the islet microvasculature. We analysed by immunohistochemistry and by flow cytometric immunophenotyping, the expression of CD34 on EC and the expressions of CD31, CD34, CD45 and CD133 on CEPC in Streptozotocin (STZ)-induced diabetic rats. Peripheral blood and tissue specimens were obtained from rats of different treatment regimens: STZ treatment, control saline (NS) and sodium citrate (CB) treatments. Blood cells were exposed to flow cytometric immunophenotyping for CD133, CD31, CD34, CD45 and CD133. While tissues from the pancreas, liver and kidney were routinely processed and stained immunohistochemically for CD34. There was a tendency of an increased in CD45-/CD133+/CD31+/CD34+ cells (0.04 ± 0.11 %) in diabetic rats compared to the controls (CB: 0.03 ± 0.04 %; Saline: 0.01 ± 0.03 %). But there was no significant statistical difference between them. The expression pattern of CD34 on the EC in the organs' vascular beds including arterioles, venules, capillaries and sinusoids was extremely heterogeneous across and within treatment regimens. The ECs in the sinusoids of the liver presented similar CD34 expression patterns across different treatment regimens, while the expression of CD34 on the ECs of sinusoidal capillaries in the pancreas vary with the treatment regimen. We conclude that the degree of endothelial cell damage is not uniform across organs' vascular beds in the rat, contrary to mice and humans. Furthermore, the sinusoids in the pancreas and the kidney may have the same degree of endothelial damage when exposed to the same deleterious causes.

RESUMEN: La hiperglucemia es una de las principales causas del daño de las células endoteliales (EC) en pacientes diabéticos. A pesar de que las células progenitoras endoteliales circulantes (CEPC) podrían utilizarse como pronóstico de las complicaciones microvasculares, hay muy poca información sobre la microvasculatura de los islotes. Se analizaron por inmunohistoquímica y por inmunofenotipificación citométrica de flujo, la expresión de CD34 en EC y las expresiones de CD31, CD34, CD45 y CD133 en CEPC en ratas diabéticas inducidas por estreptozotocina (STZ). Se obtuvieron muestras de sangre y tejidos periféricos a partir de ratas de diferentes regímenes de tratamiento: tratamiento con STZ, solución salina control (NS) y citrato de sodio (CB). Las células sanguíneas fueron expuestas a inmunofenotipado por citometría de flujo para CD133, CD31, CD34, CD45 y CD133. Mientras que los tejidos del páncreas, el hígado y el riñón fueron rutinariamente procesados y teñidos inmunohistoquímicamente para CD34. Se observó una tendencia a un aumento en las células CD45- / CD133 + / CD31 + / CD34 + (0,04 ± 0,11 %) en ratas diabéticas en comparación con los controles (CB: 0,03 ± 0,04 %; Salino: 0,01 ± 0,03 %). Pero no hubo diferencias estadísticamente significativas entre ellos. El patrón de expresión de CD34 en la EC en los lechos vasculares de los órganos incluyendo arteriolas, vénulas, capilares y sinusoides fue extremadamente heterogéneo a través de y dentro de los regímenes de tratamiento. Las EC en los sinusoides del hígado presentaron patrones de expresión de CD34 similares a través de diferentes regímenes de tratamiento, mientras que la expresión de CD34 en las CE de capilares sinusoidales en el páncreas varía con el régimen de tratamiento. Concluimos que el grado de daño de las células endoteliales no es uniforme en los lechos vasculares de los órganos en la rata, en comparación de los ratones y los seres humanos. Además, los sinusoides en el páncreas y el riñón pueden tener el mismo grado de daño endotelial cuando se exponen a las mismas causas deletéreas.

Gestational diabetes induces pancreatic beta-bells apoptosis in adult rat offspring / Diabetes gestacional induce apoptosis de células beta del páncreas en crías de ratas adultas

Several studies indicated that pancreatic ß-cell death occurs in both type 1 and type 2 diabetes. This experimental study was designed to determine the effect of gestational diabetes on the ß-cells in 16-week-old rat offspring. By this aim, adult Wistar rats aged 10-12 weeks were randomly allocated in control and diabetic groups. The diabetic group received 40 mg/kg/body weight of streptozotocin (STZ) on day zero of gestation. After delivery, diabetic offspring of GDM mothers and controls at the age of 16 weeks were sacrificed and pancreases harvested and fixed. The number of ß-cells and were counted by Gomori's method staining. Also, apoptosis in pancreas tissue of diabetic and control offspring was detected by TUNEL assay. Results showed a significant reduction in ß-cell number in offspring of GDM (p<0.05). TUNEL assay showed that the number of apoptotic cells increased in GDM compared to controls (P<0.05). This study revealed that gestational diabetes induces pancreatic beta-cells apoptosis in 16-week-old rat offspring.

Varios estudios indican que la muerte de las células ß del páncreas se produce tanto en la diabetes Tipo 1 como en la Tipo 2. Este estudio experimental fue diseñado para determinar el efecto de la diabetes gestacional en las células ß del páncreas en crías de ratas de 16 semanas. Para ello, ratas Wistar adultas de entre 10-12 semanas fueron asignadas al azar en dos grupos: control y diabetes. El grupo diabetes recibió 40 mg / kg / peso corporal de estreptozotocina (STZ) en el día cero de la gestación. Después del parto, a las 16 semanas, las crías de las madres diabéticas y controles de madres con diabetes gestacional (MDG), fueron sacrificadas para la extracción del páncreas, el cual posteriormente fue fijado. Se contó el número de células ß del páncreas mediante tinción con el método de Gomori. Además, se detectó apoptosis en el tejido del páncreas de la descendencia diabética y el grupo control mediante un ensayo TUNEL. Los resultados mostraron una reducción significativa en el número de células b en la descendencia de MDG (p <0,05). El ensayo TUNEL mostró que el número de células apoptóticas aumentó en MDG en comparación con los controles (P <0,05). Este estudio reveló que la diabetes gestacional induce apoptosis de células ß en el páncreas de crías de ratas de 16 semanas.

High-intensity interval training beneficial effects in diet-induced obesity in mice: adipose tissue, liver structure, and pancreatic islets / Efectos beneficiosos del entrenamiento con intervalos de alta intensidad en la obesidad inducida por dieta en ratones: tejido adiposo: estructura del hígado e islotes pancreáticos

The study aimed to evaluate the impact of high-intensity interval training (HIIT) on adipose tissue, pancreatic islets and liver in mice fed high-fat diet. C57BL/6 male mice were fed one of two diets: standard chow (Lean group - LE) or a high-fat diet (Obese group ­ OB). After the first 12-weeks, the animals were divided into non-trained (LE-NT and OB-NT), trained groups (LE-T and OB-T), and started the exercise protocol. The HIIT protocol in the trained animals (LE-T and OB-T) compared to their counterparts (LE-NT and OB-NT) led to a reduction in size of the pancreatic islets (LE-T vs. LE-NT -40 %, OB-T vs. OB-NT -22 %) and to an increase in insulin immunodensity in pancreatic islet (LE-T vs. LE-NT +35 %, OB-T vs. OB-NT +31 %). Apart from the above results, in adipose tissue, a decrease of the diameter of adipocytes (LE-T vs. LE-NT -23 %, OB-T vs. OB-NT -12 %), a reduction in adiposity index (LE-T vs. LE-NT -49 %, OB-T vs. OB-NT -24 %) and in the liver, a decrease in the context of hepatic steatosis (LE-T vs. LE-NT -57 %, OB-T vs. OB-NT -77 %). These metabolic changes characterize a benefits performance of the HIIT protocol in swimming. HIIT is able to mitigate the bad effects caused by high-fat diet, even with continued intake of this diet in an animal model. HIIT has the advantage of requiring only a few weekly sessions with short duration in each session. These benefits are important to motivate people who nowadays live with a lack of time condition for these activities.

El objetivo fue evaluar el impacto del entrenamiento con intervalos de alta intensidad (EIAI) sobre el tejido adiposo, el hígado y los islotes pancreáticos en ratones alimentados con dieta alta en grasas. Ratones C57BL/6, machos fueron alimentados con una de dos dietas: dieta estándar (grupo magro - MA) o una dieta alta en grasas (grupo obeso - OB). Después de las primeras 12 semanas, los animales fueron divididos en dos grupos, no entrenados (MA-NE y OB-NE) y grupos entrenados (MA-E y OB-E), y comenzaron el protocolo de ejercicio. El protocolo de IEAI en los animales entrenados (MA-E y OB-E) en comparación con sus contrapartes (MA-NE y OB-NE) condujo a una reducción en el tamaño de los islotes pancreáticos (MA-E vs. MA-NE -40 %, OB-E vs. OB-NE -22 %) y al aumento de la inmunodensidad de insulina en los islotes pancreáticos (MA-E vs. MA-NE +35 %, OB-E vs. OB-NE +31 %). Además, en el tejido adiposo se detectó una disminución del diámetro de los adipocitos (MA-E vs. MA-NE -23 %, OB-E vs. OB-NE -12 %), una reducción en el índice de adiposidad (MA-E vs. MA-NE -49 %, OB-E vs. OB-NE -24 %) y en el hígado una disminución de la esteatosis (MA-E vs. MA-NE -57 %, OB-E vs. OB-NE -77 %). Estos cambios metabólicos caracterizan una actuación beneficiosa del protocolo de EIAI en la natación. El EIAI es capaz de mitigar los efectos negativos causados por la dieta alta en grasas, incluso con la ingesta continuada de esta dieta en el modelo animal. La EIAI tiene la ventaja de requir sólo unas pocas sesiones semanales con corta duración de cada sesión. Estos beneficios son importantes para motivar a la personas en las condiciones de falta de tiempo que tienen en la actualidad.

[Nesidioblastosis in adults]

Nesidioblastosis is a rare disorder in adults characterized by diffuse proliferation of islet cells. The ideal diagnostic and therapeutic approach is still controversial. The diagnosis in our case was made after distal pancreatectomy as the treatment of insulinoma. Finally, all the remaining pancreatic tissue had to be removed [total pancreatectomy] to control episodes of hypoglycemia

Pancreatic Islet Cell Amyloidosis Manifesting as a Large Pancreas

A 39-year-old female patient presented to our hospital with epigastric pain lasting for two months. Laboratory results showed impaired glucose tolerance. Ultrasonography of the patient showed a hypoechoic, diffusely enlarged pancreas. CT revealed a large pancreas, with multiple calcifications. On MRI, a diffusely enlarged pancreas was seen hypointense on both T1- and T2-weighted images with heterogeneous enhancement after gadolinium administration. A biopsy of the pancreas revealed primary amyloidosis of islet cells. Decreased signal on T1-weighted images without inflammation findings on CT and MRI were clues for the diagnosis.

Retrospective review of cross sectional imaging findings of pancreatic non functional islet cell tumor [NFICT] and its hepatic metastases

Review and correlate the computed tomography [CT] imaging features of pancreatic Non Functional Islet Cell Tumors [NFICT] and its hepatic metastases. CT examinations of 28 patients with pathologically proven diagnosis of pancreatic NFICT and no clinical symptoms or signs attributed to hormone overproduction, performed at Mallinkrodt Institute of Radiology, Saint Louis, Missouri, USA between March 2002-July 2006, were retrospectively reviewed by two abdominal radiologists. The imaging findings were analyzed and summarized. Pancreatic NFICT size ranged from 1.2-13 cm. The commonest pattern of enhancement was hypervascular and heterogenous enhancement. The spleen was the commonest invaded nearby local structure. The commonest pattern of enhancement noted in the metastatic liver lesions was hypervascular heterogenous enhancement. 26% of the liver metastatic lesions were associated with invasion/encasement of nearby vessels. Imaging features of pancreatic NFICT can overlap with other pancreatic neoplasms. Therefore combining the imaging features of pancreatic NFICT and its hepatic metastases helps in narrowing the differential diagnosis

Chronic treatment with ethanolic extract of the leavesof Azadirachta indica ameliorates lesions of pancreatic islets in streptozotocin diabetes / Tratamiento crónico con extracto etanólico de hojas de Azadirachta indica disminuye las lesiones de los islotes pancreáticos en diabetes por estreptozotocina

Botanical drugs are complementary therapies in the management of diabetes mellitus. In this work, we studied the effects of chronic treatment of diabetic rats with A. indica (neem) on blood glucose, pancreatic islet histopathology, and oxidative status of the pancreas. Fifty-four Wistar rats (5-8 weeks old) were randomly assigned to 5 treatment groups. Hyperglycemia was induced in 34 fasted rats with a single i.p. injection of STZ (70 mg/kg bw/d). Ethanolic extract of A. indica leaves (500 mg/kg bw/d) was given orally to diabetic rats (n=12) for 50d. Glibenclamide was given (p.o) at 600 µg/ kg bw/d. In each group, blood glucose, islet histopathology, and pancreatic oxidative status, were assessed. All hyperglycemic rats in the neem-treated group had become normoglycemic at the end of week 2. By 50d, the number of viable b cells was highest in the neem-treated diabetic rats (compared with the diabetic and glibenclamide groups). Similarly, islet histology showed marked improvement in this group, in addition to improved oxidative stress. Our findings confirmed the hypoglycemic effect of neem. Besides, the improved islet morphology and oxidative status in neem-treated diabetic rats suggest the potential of this herb at improving lesions of the pancreatic islet in diabetes mellitus.

Los medicamentos a base de plantas son terapias complementarias en el manejo de la diabetes mellitus. En este trabajo se estudiaron los efectos del tratamiento crónico de ratas diabéticas con A. indica (Neem) sobre la glucosa de la sangre, la histopatología de los islotes pancreáticos, y el estado oxidativo del páncreas. Cincuenta y cuatro ratas Wistar (5-8 semanas de edad) fueron asignadas aleatoriamente a 5 grupos de tratamiento. La hiperglucemia fue inducida en 34 ratas en ayunas con una única inyección IP de STZ (70 mg/kg peso corporal/d). El extracto etanólico de hojas de A. indica (500 mg/kg de peso corporal/día) fue administrado por vía oral a ratas diabéticas (n=12) por 50d. Glibenclamida fue dada (PO) a 600 mg/kg peso corporal/d. En cada grupo, la glucosa en la sangre, la histopatología de los islotes, y el estado oxidativo de páncreas, se evaluaron. Todas las ratas de hiperglucemia en el grupo tratado con el Neem se habían convertido en normoglucémicas al final de la semana 2. Por 50d, el número de células b viables fue mayor en el Neem ratas tratadas con diabetes (en comparación con los grupos de diabéticos y glibenclamida). Del mismo modo, la histología de los islotes mostró una notable mejoría en este grupo, además de mejorar el estrés oxidativo. Nuestros resultados confirman el efecto hipoglucemiante de Neem. Además, la mejora de la morfología de los islotes y el estado de oxidación en el neem tratados con ratas diabéticas sugieren el potencial de esta hierba en la mejora de las lesiones de los islotes pancreáticos en la diabetes mellitus.

Inmunopatogenia de la diabetes mellitus tipo 1 / Immunopathology of the diabetes mellitus type 1

La diabetes mellitus tipo 1 (DM_1) es el resultado de la destrucción de las cálulas ß pancréaticas secundaria a un proceso autoinmune específico. Los autoantígenos, macrófagos, células dendríticas (DDcs), linfocitos ß y T han demostrado estar involucrados en la patogenia de la DM-1. Los autoantígenos son liberados desde las células ß, secundarios a un recambio o daño celular, siendo éstos procesados y presentados a las célular T helper por las células presentadoras de antígenos. Los macrófagos y las DCs son las primeras en infiltrar los islotes pancreáticos. Los linfocitos TCD4+ vírgenes circulantes y ubicados en los linfonodos, incluyendo los pancreáticos, pueden reconocer el complejo mayor de histocompatibilidad y los péptidos presentados por las DCs y macrófagos en los islotes. Estos LTCD4+ pueden ser activados por la interleuquina (IL)-12 liberada desde los macrófagos y DCs. Mientras este proceso ocurre, LTCD8+ específicos de células ß son activados diferenciándose en LT citotóxicos, los que son reclutados en los islotes pancreáticos. Estos, junto con los LTH1 CD4+ T activados, están involucrados en la destrucción de las células ß. Adicionalmente, las Células ß son dañadas por granzimas y perforinas liberadas desde los LTCD8+ citotóxicos y por los distintos mediadores solubles, como citoquinas y moléculas reactivas derivadas del oxígeno, liberados desde macrófagos activados a nivel de los islotes. Es así como los macrófagos activado, los LTH1 CD4+ y CD8+ actúan sinérgicamente destruyendo las células ß, desencadenando la DM-1.

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.

Isolated islets in diabetes research.

This review highlights some recent developments and diversified applications of islets in diabetes research as they are rapidly emerging as a model system in biomedical and biotechnological research. Isolated islets have formed an effective in vitro model in antidiabetic drug development programme, screening of potential hypoglycaemic agents and for investigating their mechanisms of action. Yet another application of isolated islets could be to understand the mechanisms of beta cell death in vitro and to identify the sites of intervention for possible cytoprotection. Advances in immunoisolation and immunomodulation protocols have made xeno-transplantation feasible without immunosuppression thus increasing the availability of islets. Research in the areas of pancreatic and non pancreatic stem cells has given new hope to diabetic subjects to renew their islet cell mass for the possible cure of diabetes. Investigations of the factors leading to differentiation of pancreatic stem/progenitor cells would be of interest as they are likely to induce pancreatic regeneration in diabetics. Similarly search for the beta cell protective agents has a great future in preservation of residual beta cell mass left after diabetogenic insults. We have detailed various applications of islets in diabetes research in context of their current status, progress and future challenges and long term prospects for a cure.

Genesis de la mellitus tipo 1 / Genesis of the mellitus type I

La incidencia de la Diabetes Tipo 1 ha aumentado durante los últimos decenios en todo el mundo, representando en nuestro medio la séptima causa de muerte y afectando aproximadamente a un millón de venezolanos. De acuerdo a la OMS se clasifica en: Autoinmune (tipo A y tipo B) e idiopática. Esta enfermedad se considera como el resultado de una serie de factores genéticos (asociados a la región HLA-D del MHC clase II; principalmente es el locus HLA-DQ) y ambientales (relacionados con el estilo de vida del paciente e infecciones virales principalemente en virus coxsackie) que medían la activación del sistema inmunológico del individuo provocando de esta manera la destrucción de las células beta pancreáticas por diferentes mecanismos: pérdida de la Autotolerancia, Directo "Reconocimiento de Unión" e Indirecto "Unión-Activación" y como consecuencia la aparición de las manifestaciones clínicas de la enfermedad. La DM tipo 1 cursa con un período asintomático que se caracteriza por una infiltración de los islotes por monocitos/macrófagos y células T citotóxicas activadas. Este estado en el que se encuentran el paciente mientras se está produciendo (de forma indetectable), la agregación inmunitaria se denomina PRE-DIABETES, posteriormente las reservas de insulina van disminuyendo constantemente hasta hacerse insuficientes y es cuando se manifiesta clínicamente la DM.

Indução in vitro da trans-diferenciação de células ovais hepáticas em estruturas semelhantes às ilhotas pancreáticas / In vitro induction of hepatic oval cell of hepatic transdifferentiation into structures similar to pancreatic islets

Embora as células-tronco possuam grande capacidade de diferenciação em diversos tipos celulares no organismo, tanto "in vivo" como "in vitro", a produção de células endócrinas pancreáticas e de células produtoras de insulina, a partir destes tipos celulares em animais adultos, não está completamente demonstrada. A proliferação das células ovais hepáticas (COH) pode ser induzidas pela administração / Although stem cells have the ability to differentiale "in vivo" and "in vitro" into several types tof cells in the body, the production of endocrine pancreatic cells and insulin producing cells from adult stem cells is not completely elucidated. Hepatic oval cell (Hoc) proliferation can be induced by 2-AAF administration. Studies have showed that HOC can transdifferentiate 'in vitro' into endocrine pancreatic cells, when cultured for long periods and with high glucose concentrations. The aim of this study was to induce rat HOC transfifferentiation in shorter...

A Large Malignant Insulinoma: Case Report with Endosonographic, Immunohistochemical and Ultrastructural Features

Malignant insulinoma in the beta cells of the pancreatic islet is rare and usually presented as hypoglycemia. We report a case of large malignant insulinoma in a 53-year-old Korean woman. A presumptive clinical diagnosis was made before surgery, based on the high plasma insulin-to-glucose ratio and a large solitary heterogeneous pancreatic mass by abdominal computed tomography and endosonography. The tumor measured 5.8X4.7X4.5 cm in dimension and showed capsular invasions and metastases in two of four peripancreatic lymph nodes. The tumor cells were strongly immunoreactive to insulin and had a high Ki-67 labeling index (13%) and atypical membranous electron-dense granules, ranging from 120 to 400 nm in diameter, in the cytoplasm on electron microscopy. The patient was treated by distal pancreatectomy with splenectomy and rapidly recovered without neurohypoglycemic symptoms. This case showed not only lymph node metastases, the most reliable parameter for malignancy in pancreatic endocrine tumors, but also other valid diagnostic clues, such as high Ki-67 labeling index, heterogeneous enodosonographic findings, capsular invasions with large tumor and pure atypical secretory granules.

Influence of the pineal gland on the physiology, morphometry and morphology of pancreatic islets in rats

To investigate the influence of the pineal gland through melatonin secretion on the physiological and morphological parameters of pancreatic islets, we studied the plasma biochemistry and morphological and morphometric characteristics of the endocrine pancreas of male Wistar rats. The animals were distributed into five groups of ten rats each: NC - normal control group; NS - sham-operated group; Px (25) - pinealectomised group, studied 15-25 days after surgery; Px (70) - pinealectomised group, studied 60-70 days after surgery; ALX - alloxan monohydrate-treated group. Data are analyzed statistically by ANOVA and by the Kruskal-Wallis test. Although there was no significant difference in plasma glucose or insulin levels between the Px (25), Px (70) and NC groups, Px (25) animals showed a tendency to increased glucose and reduced insulin levels. The ALX group showed a clear elevation of plasma glucose and a reduction of plasma insulin compared to the other groups. Morphometric analysis showed a larger pancreatic islet area and a lower pancreatic islet density in the pancreas of Px (70) animals and an increase in degenerative pathological processes in the pancreatic islets of the Px (25) and ALX groups. The present results suggest that melatonin, in addition to acting on tissue sensitivity to insulin (as reported in other studies), affects the secretory action of beta cells, as demonstrated by the morphological and morphometric changes observed in pinealectomised animals

Islet cell hyperplasia of the pancreas presenting as hyperinsulinemic hypoglycemia in an adult

A 72-year-old man who had suffered several episodes of syncope was diagnosed as having hyperinsulinemic hypoglycemia. Although imaging studies and percutaneous transhepatic portal venous sampling did not reveal the existence of any tumors in the pancreas, distal pancreatectomy was performed because the possibility of a small pancreatic endocrine tumor could not be completely rejected. External examination of the surgically removed pancreas did not reveal any tumors. Microscopically, the pancreas exhibited diffuse islet cell hyperplasia without nesidioblastosis. The patient remains euglycemic and has tolerated 24-hour fasting without any medication for a period of 10 months after the operation.

Alteraçöes anatomopatológicas do pâncreas em chagásicas crônicas: dados preliminares / Pancreatic anatomopathologic changes in chronic chagasic women. preliminary data

Comparação da freqüência de alterações morfológicas e morfométricas no pâncreas de mulheres chagásicas (n=6) com idade igual ou acima de 40 anos e controles não-chagásicas (n = 4), pareadas quanto à idade (59,8 + 11,5 versus 59,0 + 6,3 anos), percentagem de cor branca (33,3 por cento versus 50,0 por cento) e índice de massa corporal (22,3 + 7,0 versus 18,8 + 2,1 Kg/m2). Não houve diferença morfométrica significante entre as ilhotas pancreáticas de pacientes chagásicas e de pacientes controles submetidas a necropsia. Entretanto, foram observadas diferencas morfológicas entre os grupos, com menor número de neurônios intrapancreáticos e maior freqüência de infiltrados leucocitários perineurais entre as mulheres chagásicas. Essa possível desnervação intrapancreática poderia estar relacionada a alterações no metabolismo dos hidratos de carbono, inclusive hiperglicemia e diabetes mellitus, observadas em algumas chagásicas crônicas.

Effects of BCG, lymphotoxin and bee venom on insulitis and development of IDDM in non-obese diabetic mice

To investigate whether BCG, lymphtoxin (LT) or bee venom (BV) can prevent insulitis and development of diabetes in non-obese diabetic (NOD) mice, we measured the degree of insulitis and incidence of diabetes in 24 ICR and 96 female NOD mice. NOD mice were randomly assigned to control, BCG-, LT-, and BV-treated groups. The BCG was given once at 6 weeks of age, and LT was given in 3 weekly doses from the age of 4 to 10 weeks. The BV was injected in 2 weekly doses from the age of 4 to 10 weeks. Diabetes started in control group at 18 weeks of age, in BCG group at 24 weeks of age, and in LT- or BV-treated group at 23 weeks of age. Cumulative incidences of diabetes at 25 weeks of age in control, BCG-, LT-, and BV-treated NOD mice are 58, 17, 25, and 21%, respectively. Incidence and severity of insulitis were reduced by BCG, LT and BV treatment. In conclusion, these results suggest that BCG, LT or BV treatment in NOD mice at early age inhibit insulitis, onset and cumulative incidence of diabetes.