Essential Role of Protein Arginine Methyltransferase 1 in Pancreas Development by Regulating Protein Stability of Neurogenin 3

BACKGROUND: Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells. Recent studies have revealed that PRMT1 plays important roles in the development of various tissues. However, its role in pancreas development has not yet been elucidated. METHODS: Pancreatic progenitor cell-specific Prmt1 knock-out (Prmt1 PKO) mice were generated and characterized for their metabolic and histological phenotypes and their levels of Neurog3 gene expression and neurogenin 3 (NGN3) protein expression. Protein degradation assays were performed in mPAC cells. RESULTS: Prmt1 PKO mice showed growth retardation and a severely diabetic phenotype. The pancreatic size and β-cell mass were significantly reduced in Prmt1 PKO mice. Proliferation of progenitor cells during the secondary transition was decreased and endocrine cell differentiation was impaired. These defects in pancreas development could be attributed to the sustained expression of NGN3 in progenitor cells. Protein degradation assays in mPAC cells revealed that PRMT1 was required for the rapid degradation of NGN3. CONCLUSION: PRMT1 critically contributes to pancreas development by destabilizing the NGN3 protein.

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.

Co-Culture of alpha TC-6 Cells and beta TC-1 Cells: Morphology and Function

BACKGROUND: In vitro experiments using only beta-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially alpha- and beta-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with alpha- and beta-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. METHODS: alpha TC-6 cells and beta TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5x10(5)) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). RESULTS: alpha TC-6 and beta TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. beta TC-1 cells showed both beta-beta and beta-alpha cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than beta TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for beta-cells alone (P=0.04). Compared to islets, the alpha-/beta-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). CONCLUSION: alpha TC-6 and beta TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

Immunohistochemical evaluation of the goat forestomach during prenatal development

Here we report the detection and distribution of synaptophysin (SPY), non-neuronal enolase (NNE), glial fibrillary acidic protein (GFAP), vimentin (VIM), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) expression in the goat forestomach during prenatal development. A total of 140 embryos and fetuses were examined to evaluate protein expression from the first stage of prenatal life until birth. In all cases, SPY immunoreactivity was detected at 53 days gestation in the lamina propria-submucosa, tunica muscularis, serosa, and myenteric plexuses. Immunoreactivity to NNE was observed at 64 days gestation in the same locations as well as the epithelial layer. Glial cells were found at 64 days as indicated by signals corresponding to GFAP and VIM at 39 days. Positive staining for NPY and VIP was observed at 113, 75, and 95 days in the rumen, reticulum, and omasum, respectively, in the lamina propria-submucosa, tunica muscularis, and myenteric plexuses of each of these gastric compartments. These findings indicate possible preparation of the fetal goat forestomach for postnatal function. Compared to other ruminant species, neuroendocrine cells, glial cells and peptidergic innervations markers were detected earlier compared to sheep but at around the same stage as in deer.

Culture of pancreatic progenitor cells in hanging drop and on floating filter / 中国医学科学院学报

<p><b>OBJECTIVE</b>To construct a method to culture pancreatic progenitor cells in hanging drop and on floating filter,and to examine if pancreatic progenitor cells can differentiate into mature endocrine cells with this method.</p><p><b>METHODS</b>Murine embryos at day 12.5 were isolated and digested into single cells,which were then cultured in hanging drop for 24h and formed spheres.Spheres were cultured on the filter for 6 days,which floated in the dish containing medium.During culture,the expressions of pancreas duodenum homeobox-1(PDX-1)and neurogenin3(Ngn3)were determined.The expressions of endocrine and exocrine markers,insulin,glucagon,and carboxypeptidase(CPA)were determined on day 7 by immunohistochemistry.Insulin secretion of spheres stimulated by glucose was detected by ELISA.The changes of pancreatic marker expressions during culture were monitored by real-time polymerase chain reaction(PCR).</p><p><b>RESULTS</b>One day after the culture,there were still a large amount of PDX-1 positive cells in pancreatic spheres,and these cells proliferated.On day 3,high expression of Ngn3 was detected,and the Ngn3-positive cells did not proliferate.On day 7,The expressions of endocrine and exocrine markers in the differentiated pancreatic progenitor cells were detected,which were consistent with that in vivo.Insulin was secreted by spheres upon the stimulation of glucose.</p><p><b>CONCLUSION</b>In hanging drop and on floating filter,pancreatic progenitor cells can differentiate into mature endocrine cells.</p>

The influence of selected pathological states on the somatostatin-like immunoreactive (SOM-LI) endocrine cells in the mucosal layer of the porcine descending colon

This study reports on changes in the number of somatostatin-like immunoreactive (SOM-LI) endocrine cells in the porcine descending colon, caused by chemically driven inflammation, axotomy and proliferative enteropathy (PE). The distribution pattern of SOM-LI endocrine cells has been studied using the routine single-labelling immunofluorescence technique. Semi-quantitative evaluation of the number of the SOM-immunostained endocrine cells within the mucosal layer of the porcine descending colon has been based on counting of all endocrine cells immunoreactive to SOM per unit area (0,1 mm²). Under physiological conditions the number of SOM-LI endocrine cells has been shown to constitute 3,30±0,22. All applied pathological processes resulted in changes in the SOM-like immunoreactivity, which varied in particular processes studied. The number of SOM-LI endocrine cells increased to 6,28±0,31 and 4,43±0,35 during chemically driven inflammation and proliferative enteropathy, respectively, and decreased to 1,17%±0,16 after axotomy. The obtained results suggest that SOM-LI endocrine cells may participate in various pathological states within porcine descending colon and their functions probably depend on the type of pathological factor.(AU)

Establishment of a new method to induce the differentiation of embryonic pancreatic cells into mature endocrine cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish a new culture method to induce the differentiation of embryonic pancreatic cells into mature endocrine cells.</p><p><b>METHODS</b>Mouse embryos at day 12.5 were used and embryonic pancreata were isolated. The isolated embryonic pancreata were cultured on the filter for 7 days, which floated in the dish containing medium. During culture, the expression of pancreas duodenum homeobox-1 (PDX-1), a pancreatic stem cell marker, was examined at day 1. The expression of neurogenin 3 (Ngn3), a pancreatic progenitor cell marker, was examined at day 3. The expressions of endocrine and exocrine markers, insulin, glucagon, and carboxypeptidase (CPA) were examined at day 7 by immunohistochemistry. The kinetics of pancreatic marker expression during culture was assayed by real-time PCR.</p><p><b>RESULTS</b>Many pancreatic stem cells still existed in embryonic pancreata cultured for 1 day; meanwhile, these pancreatic stem cells proliferated in high rate. A large amount of pancreatic progenitor cells were found in embryonic pancreata cultured for 3 days.Pancreatic stem/progenitor cells differentiated into mature endocrine and exocrine cells in embryonic pancreata after having been cultured for 7 days. Furthermore, the expression pattern of pancreatic marker is consistent with that in vivo.</p><p><b>CONCLUSION</b>We successfully established a new culture method, with which embryonic pancreatic cells can efficiently differentiate into mature endocrine cell.</p>

Quantification of argyrophillic, argentaffin and insulin immunoreactive cells in the small intestine in the opossum Didelphis aurita (Wied-Neuwied, 1826) / Quantificação das células argirófilas, argentafins e imunorreativas à insulina nos diferentes segmentos do intestino delgado do gambá Didelphis aurita (Wied-Neuwied, 1826)

The objective of this study was to quantify argyrophillic, argentaffin and insulin immunoreactive endocrine cells in the different segments of the small intestine of Didelphis aurita and measure probable differences in the number of these cells between adult and post-pubertal animals. Biological material consisted of ten male and female opossums specimen, divided in two groups according to weigh. The utilized staining techniques were Grimelius, modified Masson-Fontana and direct immunoperoxidase. Results indicated a predominance of argyrophillic cells in the small intestine of opossums from class 1 and 2, with an average of 52.58 and 56.15 cells mm-2, respectively; of which, the average number of total endocrine cells, argyrophillic and argentaffin cells decreased distally in the intestinal segments of opossums from classes 1 and 2. No significant difference was observed for the insulin immunoreactive cells between the intestinal segments of animals from class 2. A greater number of insulin immunoreactive cells was encountered in the jejunum and ileum of animals from class 2 when compared to the same segment in animals from class 1.

Os objetivos deste trabalho foram quantificar as células endócrinas argirófilas, argentafins e imunorreativas à insulina nos diferentes segmentos do intestino delgado de gambás Didelphis aurita e mensurar prováveis diferenças no número destas células entre animais adultos e pós-púberes. Dez exemplares de gambás D. aurita machos e fêmeas foram divididos em dois grupos de acordo com o peso. As técnicas de coloração utilizadas foram Grimelius, Masson-Fontana modificado e Imunoperoxidase direta. Os resultados indicaram um predomínio das células argirófilas no intestino delgado de gambás da classe 1 e 2, com uma média de 52,58 e 56,15 células mm-2, respectivamente. O número médio de células endócrinas totais, células argirófilas e argentafins decresceu distalmente nos segmentos intestinais dos gambás das classes 1 e 2. Nenhuma diferença significativa foi observada para as células imunorreativas à insulina entre os segmentos intestinais dos animais da classe 2. Foi encontrado maior número de células imunorreativas à insulina no jejuno e íleo de animais da classe 2 quando comparado ao mesmo segmento em animais da classe 1.

Ghrelin- and preproghrelin-immunoreactive cells in atrophic body gastritis / Células imunorreativas a grelina e preprogrelina na gastrite atrófica do corpo

INTRODUCTION: Ghrelin is a 28 amino acid peptide mainly secreted by endocrine cells of the gastric mucosa, which is believed to have a modulating effect on cell growth. OBJECTIVE: To assess the presence of ghrelin and its precursor preproghrelin molecule in endocrine hyperplasias associated with atrophic body gastritis (ABG). MATERIAL AND METHODS: Endoscopic biopsies from 54 patients with ABG were processed for immunohistochemistry and specific antibodies against ghrelin, preproghrelin and chromogranin were applied. We assessed the immunoreactive cells in endocrine hyperplasia from the atrophic mucosa and intestinal and pseudo-antral metaplasia areas. RESULTS: There was ghrelin expression in a variable number of hyperplastic endocrine cells from all patients studied. There was a statistically significant difference in the number of hyperplastic nodules with more than 50 percent immunostained cells for chromogranin and ghrelin and for chromogranin and preproghrelin. The mean number of hyperplastic nodules identified by chromogranin was 8.6 per patient. Most nodules were immunoreactive to ghrelin and preproghrelin. The presence of ghrelin and preproghrelin expression was uncommon in glands showing intestinal metaplasia: four (9.5 percent) and nine (21.4 percent) cases, respectively. In contrast, they were relatively frequent in pseudo-antral metaplasia areas: 37 (72.5 percent) and 26 (50.9 percent) cases, respectively. CONCLUSION: Ghrelin- and preproghrelin-immunoreactive cells are frequently present in endocrine hyperplasias associated with ABG. However, further studies are required to determine to what extent these hormones act as modulators of hyperplastic nodular growth and evolution.

INTRODUÇÃO: Grelina é um peptídeo de 28 aminoácidos secretado principalmente pelas células endócrinas da mucosa gástrica, acreditando-se que apresente ação moduladora relacionada com o crescimento celular. OBJETIVO: Estudar a presença de grelina e da molécula precursora preprogrelina na hiperplasia endócrina associada à gastrite atrófica do corpo (GAC). MATERIAL E MÉTODOS: Biópsias endoscópicas de 54 pacientes com GAC foram processadas para imuno-histoquímica, e anticorpos específicos contra grelina, preprogrelina e cromogranina foram utilizados. As células imunorreativas foram examinadas na hiperplasia endócrina presente na mucosa atrófica e nas áreas de metaplasia intestinal e pseudoantral. RESULTADOS: Ocorreu expressão de grelina em número variável de células endócrinas hiperplásicas em todos os pacientes estudados. Diferença estatisticamente significativa foi encontrada entre a frequência de nódulos hiperplásicos com mais de 50 por cento de células imunomarcadas por cromogranina e grelina ou por cromogranina e preprogrelina. O número médio de nódulos hiperplásicos por paciente demonstrado pela cromogranina foi de 8,6. A maioria desses nódulos apresentou células imunorreativas para grelina e preprogrelina, respectivamente, 5,1 e 5,6, em média. A presença da expressão imuno-histoquímica de grelina e preprogrelina foi incomum em glândulas exibindo metaplasia intestinal, respectivamente, em quatro (9,5 por cento) e nove (21,4 por cento) casos e foram frequentes nas áreas de metaplasia pseudoantral em, respectivamente, 37 (72,5 por cento) e 26 (50,9 por cento) casos. CONCLUSÃO: Células imunorreativas a grelina e preprogrelina estão presentes na hiperplasia endócrina associada à GAC. Entretanto, mais estudos são necessários para saber até que ponto esses hormônios estão atuando como moduladores do crescimento e a evolução desses nódulos hiperplásicos.

The esophagus of the crocodilian Caiman latirostris (Reptilia, Crocodylia ): histologia, histochemical, and immunohistochemical study

The purpose of this study was to analyze the esophageal morphology of Caiman latirostris using histochemicaland immunohistochemical techniques. The mucosae layer is composed of a pseudostratified columnarepithelium with goblet cells that occasionally form intra-epithelial glands. The goblet cells showed differentaffinity for the histochemical techniques. The lamina propria is composed of loose connective tissue with bloodvessels. The smooth muscle fibers that compose the muscularis mucosa are thick and form a clear demarcationbetween the mucosa layer and adjacent submucosa. There are no glands in the esophageal submucosa. Themuscle layer is composed a circular internal layer and a longitudinal external one. The adventitia layer iscomposed of loose connective tissue and blood vessels. The serotonin immunoreactive (IR) cells were notpreferentially distributed in any region of the epithelium, ranging from the base of the intra-epithelial gland tothe connection to the lumen. Somatostatina, glucagon and CCK IR cells were not detected.

Influence of Exposure to Extremely Low Frequency Magnetic Field on Neuroendocrine Cells and Hormones in Stomach of Rats

Extremely low frequency magnetic fields (ELF-MF) have the ability to produce a variety of behavioral and physiological changes in animals. The stomach, as the most sensitive part of the neuroendocrine organ of the gastrointestinal tract, is crucial for the initiation of a full stress response against all harmful stress. Thus, the purpose of this study was to examine whether ELF-MF stimuli induce changes in the activity of neuroendocrine cells, considering their involvement in endocrine or paracrine effect on surrounding cells. The exposure to ELF-MF (durations of 24 h and 1 or 2 weeks, 60 Hz frequency, 0.1 mT intensity) altered the distribution and occurrence of gastrin, ghrelin and somatostatin-positive endocrine cells in the stomach of rats. The change, however, in the secretion of those hormones into blood from endocrine cells did not appear significantly with ELF-MF exposure. Comparing with sham control, ELF-MF exposure for 1 and 2 week induced an increase in BaSO4 suspension propelling ratio of gastrointestinal tract, indicating that ELF-MF affects gastrointestinal motility. Our study revealed that ELF-MF exposure might influence the activity of endocrine cells, an important element of the intrinsic regulatory system in the digestive tract. The pathophysiological character of these changes and the mechanism responsible for neuroendocrine cell are still unclear and require further studies.

Changes of colonic endocrine cells in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis / 대한수의학회지

In this study, immunohistochemistry was used to examine the changes in the density of colonic endocrine cells - argyrophil and argentaffin cells, chromogranin A (CGA), serotonin, somatostatin and glucagon-containing cells in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Ulcerative colitis was induced by the instillation of 10 mg of TNBS into the colonic lumen through the anus. To confirm the inducement of ulcerative colitis, the macroscopic and microscopic scores as well as the colonic myeloperoxidase (MPO) activities were monitored for 8 days after TNBS instillation in the colonic lumens. In addition, the number of argyrophil and argentaffin cells, CGA, serotonin, somatostatin and glucagon-immunoreactive cells were counted in the colonic mucosa, respectively. After TNBS instillation into the lumen of the colon from the anus in rats, increases in macroscopic and microscopic scores in the colon tissues were observed along with increases in the colonic MPO activities. Therefore, ulcerative colitis was relatively well induced by the TNBS instillations. Marked decreases in the number of colonic endocrine cells were detected in the TNBS-treated animal compared to the sham control. These results suggest that colonic endocrine cells were also disrupted by TNBS-induced ulcerative colitis.

Cell Replacement and Regeneration Therapy for Diabetes / 당뇨병

Reduction of beta cell function and a beta cell mass is observed in both type 1 and type 2 diabetes. Therefore, restoration of this deficiency might be a therapeutic option for treatment of diabetes. Islet transplantation has benefits, such as reduced incidence of hypoglycemia and achievement of insulin independence. However, the major drawback is an insufficient supply of islet donors. Transplantation of cells differentiated in vitro or in vivo regeneration of insulin-producing cells are possible approaches for beta cell/islet regenerative therapy. Embryonic and adult stem cells, pancreatic ductal progenitor cells, acinar cells, and other endocrine cells have been shown to differentiate into pancreatic beta cells. Formation of fully functional beta cells and the safety of these cells are critical issues for successful clinical application.

Distribution and ontogeny of gastrin- and serotonin-immunoreactive cells in the proventriculus of developing chick, Gallus gallus domestica

The ontogeny and distribution of gastrin- and serotonin-immunoreactive (IR) cell in the proventriculus of chicks (Gallus gallus domestica, n = 60) in different growth periods was examined immunohistochemically using antisera specific to gastrin and serotonin. Gastrin and serotonin-IR cells were detected in chick proventriculus. Gastrin-IR cells were first evident after 12 days of incubation in lamina epithelialis and compound glands, while serotonin-IR cells were observed only in compound glands at that same time. Gastrin-IR and serotonin-IR cells increased in frequency on incubation day 14 and 16, respectively. Towards the end of incubation, gastrin- and serotonin-IR cell numbers decreased. In adult chicken, both IR cells were present but not lower numbers. The observations demonstrate the presence of gastrin- and serotonin-IR cells in the proventriculus of developing chicks in temporally changing frequencies.

Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells / 당뇨병

BACKGROUND: Despite a recent breakthough in human islet transplantation for treating type 1 diabetes mellitus, the limited availability of donor pancreases remains a major obstacle. Endocrine cells within the gut epithelium (enteroendocrine cells) and pancreatic beta cells share similar pathways of differentiation during embryonic development. In particular, K-cells that secrete glucose-dependent insulinotropic polypeptide (GIP) have been shown to express many of the key proteins found in beta cells. Therefore, we hypothesize that K-cells can be transdifferentiated into beta cells because both cells have remarkable similarities in their embryonic development and cellular phenotypes. METHODS: K-cells were purified from heterogeneous STC-1 cells originating from an endocrine tumor of a mouse intestine. In addition, a K-cell subclone expressing stable Nkx6.1, called "Kn4-cells," was successfully obtained. In vitro differentiation of K-cells or Kn4-cells into beta cells was completed after exendin-4 treatment and serum deprivation. The expressions of insulin mRNA and protein were examined by RT-PCR and immunocytochemistry. The interacellular insulin content was also measured. RESULTS: K-cells were found to express glucokinase and GIP as assessed by RT-PCR and Western blot analysis. RT-PCR showed that K-cells also expressed Pdx-1, NeuroD1/Beta2, and MafA, but not Nkx6.1. After exendin-4 treatment and serum deprivation, insulin mRNA and insulin or C-peptide were clearly detected in Kn4-cells. The intracellular insulin content was also increased significantly in these cells. CONCLUSION: K-cells are an attractive potential source of insulin-producing cells for treatment of type 1 diabetes mellitus. However, more experiments are necessary to optimize a strategy for converting K-cells into beta cells.

Efecto de esteroides sexuales sobre la función endocrina adipocitaria e insulinosensibilidad periférica / Effect of sexual steroids over the adipocyte and outlying insulin sensitivity

Es conocido que las hormonas esteroideas sexuales modulan la composición corporal y otras funciones endocrinas. El objetivo del presente trabajo fue estudiar el impacto de la administración de esteroides sexuales sobre la insulinosensibilidad periférica y la función secretora adipocitaria. Grupos de ratas hembra recibieron vehículo (C) o valerato de E2 o propionato de T. Se monitoreó el peso corporal y la ingesta de alimento hasta el día experimental, que fueron sacrificados en condición basal o sometidos a un test de sobrecarga con glucosa. Se evaluaron las concentraciones de leptina, E2, T, glucosa, triglicéridos e insulina (INS). Se ponderó el tejido adiposo parametrial y se aislaron los adipocitos e incubaron con o sin INS. E2 indujo una temprana (p < 0,05) hipofagia, contrariamente, T indujo una moderada (p < 0,05) hiperfagia. Los animales E2 resultaron con menor peso y masa adiposa parametrial que los C (p < 0,05). Los niveles plasmáticos no se modificaron en los animales E2 ni T, salvo el desarrollo de hiperleptinemia en el grupo E2 (p < 0,05). El test de tolerancia a la glucosa mostró (p < 0,05) aumento y disminución en la insulinosensibildad en los animales E2 y T, respectivamente. Finalmente, los adipocitos aislados de animales E2 como los T desarrollaron una disminuida (p < 0,05 vs. C) respuesta a INS. Nuestro estudio pone en evidencia los efectos de E2 y T sobre la sensibilidad a insulina y la función adipocitaria.

Sex hormones are known to modulate body composition and endocrine functions. The aim of the present study was to analyze the impact of sexual steroids administration on the outlying insulin-sensibility and adipocyte secretory function. Groups of female rats received either vehicle (C), E2 valerate, or T propionate. Daily food intake and body weight were recorded until sacrifice under basal conditions or after high glucose load test. Plasma concentrations of leptin, E2, T, glucose, triglycerides, and insulin (INS) were evaluated. The parametrial adipose tissue was pondered and adipocytes were isolated and then incubated with or without INS. E2 induced early hypophagia (p< 0,05); contrarily, T induced moderate hyperphagia (p<0,05). Weight and fatty parametrial mass values were lower for E2- than C-treated animals (p<0,05). Plasma levels remained unmodified either for E2 or T groups, though E2 animals developed hyperleptinemia (p<0.05). The high glucose load test showed increased and decreased insulin-sensitivity (p<0.05) in E2 and T groups, respectively. Finally, E2 and T isolated adipocytes were less sensitive to insulin-induced leptin secretion than C cells (p<0.05 vs. C). Our study reveals that E2 and T hormones affect sensibility to insulin as well as adipocyte functions.

The Pancreatic Tissue Regeneration and Molecular Regulators / 대한해부학회지

Pancreas is a unique organ that produces and secretes digestive enzymes to alimentary tube and supplies endocrine hormones regulating metabolic homeostasis. In the postnatal stage, pancreatic tissue is maintained by a simple proliferation of the preexisting cells. It has been known that tissue regeneration rarely occurs in the normal adult pancreas, particularly in the human pancreas. However regeneration of pancreatic tissue can be induced experimentally following pancreatic injuries in animal models. Regeneration occurs at the site of tissue injury by forming new lobules, so called 'neogenic lobule', that consist of the immature pancreatic tissues of both exocrine and endocrine components. We postulate that regeneration is instigated from the small tubular structures with elongated epithelial cells (neogenic ductules) which grow to ducts and acini for exocrine neogenesis, as well as to islet cells for endocrine tissue formation. As a sequential process of neogenic regeneration, the regenerating tissue becomes heterogeneous in tissue composition. Neogenic lobules in earlier regenerating stage were mainly composed of neogenic ductules which are substituted with developing acini in later stages. The endocrine cells, including insulin secreting beta cells, are also derived from the stem/precursor cells in neogenic ductules. After budding off from the neogenic ductules, the primitive endocrine cells continue to proliferate and differentiate, forming a large cell cluster or primitive islet. Such neogenic regeneration differs, but not completely, from pancreas development during fetal organogenesis. We found that the pancreatic regeneration is regulated by the several biological factors including nestin, clusterin and INGAP which are not involved in embryonic pancreas development. We suggest that the stem/precursor cells are recapitulated and regenerated to functional cells, and stem cell-derived pancreatic regeneration could provide a source of the pancreatic cells, particularly insulin secreting beta cells for cell replacement therapy of diabetes.

A Case of Surgical Treatment of Nesidioblastosis with Hyperinsulinemic Hypoglycemia in an Adult

Nesidioblastosis is a rare disorder, and it usually considered as a cause of neonatal hyperinsulinemic hypoglycemia. A 35 year-old-woman with hyperinsulinemic hypoglycemia was admitted in an unconscious condition. Abdominal CT, pancreas MRI and celiac angiography with an intra-arterial calcium stimulation test revealed a suspicious insulin-producing tumorous lesion in the head of pancreas. The patient underwent enucleation of the pancreas head tumor under the initial diagnosis of insulinoma. However, the tumor was confirmed histologically as nesidioblastosis that showed ductoendocrine proliferations and numerous small endocrine cell groups. Nesidioblastosis is classified into a focal type and a diffuse type, which are characterized by different clinical outcomes. The patient in our case showed a normal blood glucose level after operation, which is often the case for the focal type. Herein, we report this very rare case of adult nesiodioblastosis that was successfully treated by surgical resection.

Pancreatic Exocrine and Endocrine Cell Differentiation during Pancreatic Regeneration / 한양의대학술지

Pancreatic tissue is maintained by a simple proliferation of the preexisting cells in adulthood, whereas, they are dynamically derived from precursor/ stem cells from ductal epithelia during prenatal life. It has been known that tissue regeneration rarely occurs in the normal adult pancreas, particularly in the human pancreas. However, regeneration can be experimentally induced in the adult pancreas in response to various tissue injuries such as partial resection, pancreatitis by obstruction of the duct, and chemical insults. Regenerating pancreatic tissue shares a common morphogenic feature of "neogenic regeneration" in all regenerating animal models. Neogenic regeneration occurs at the site of tissue injury by forming small tubular structures with elongated epithelial cells (ductules) which grow to form pancreatic ducts and acini. The endocrine cells, including insulin secreting beta cells, are also derived from these ductules. As a sequential process of neogenesis, the regenerating tissue becomes heterogeneous in composition. Some areas were composed by tubules and ductules in surrounding loose connective tissue while others were denser with differentiating acini derived from tubules or ductules. Such neogenic regeneration mimics tissue development during fetal pancreatic organogenesis. In the process of pancreatic neogenesis, we found unique expressions of bioactive proteins such as nestin and clusterin as morphogenic factors. It is likely that the stem/precursor cells could be recapitulated and regenerated to functional cells, including endocrine and exocrine pancreatic cells with acinar and ductal cells during neogenic regeneration of the pancreas.