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Impaired glucose tolerance in acute pancreatitis

World Journal of Gastroenterology 2015年第24期21卷 7367-7374页

作者： kazuhiro kikuta Atsushi Masamune Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine

Acute pancreatitis(AP) is an acute inflammatory disease of the exocrine pancreas. In spite of the pivotal role of the endocrine pancreas in glucose metabolism, the impact of impaired glucose tolerance on AP has not been fully elucidated. A meta-analysis of seven observational studies showed that type 2 diabetes mellitus(DM) was associated with an increased risk of AP. The increased risk of AP shown in the meta-analysis was independent of hyperlipidemia, alcohol use and gallstones. Antidiabetic drugs including incretins might increase the risk of AP, but no intervention trials have confirmed this. Although a controversial finding, DM seems to be associated with severe attacks and organ failure in AP. We analyzed the results of a nationwide epidemiological survey of AP in Japan. We studied the impact of pre-existing DM on the clinical course of AP in 1954 cases for which information on DM status was available at the onset of AP. The prevalence of DM in AP patients(12.8%) was higher than that in the general population in Japan(10.5%). AP patients with DM had higher morbidity of cardiovascular and renal failure than those without DM. About 35% of the idiopathic AP patients with DM had renal failure. The mortality of AP patients with DM(4.0%) was higher than that of AP patients without DM(1.7%). If stratified by etiology, idiopathic, but not alcoholic or biliary, AP patients with DM were predisposed to increased mortality(9.7%). In conclusion, impaired glucose tolerance might have an impact on the development and clinical outcome of AP. However, the impact might depend on the cause of hyperglycemia, the condition of DM including severity, duration and treatment, and the characteristics of the AP patients including age, etiology and comorbidity.

关键词： Alcohol Diabetes mellitus Epidemiology Gallstone Mortality Organ failure

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Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells

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World Journal of Gastroenterology 2005年第22期11卷 3385-3391页

作者： Atsushi Masamune Masahiro Satoh kazuhiro kikuta Noriaki Suzuki Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai Japan

AIM: To clarify the role of Janus kinase-signal transducersand activators of transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced proliferation in activated pancreatic stellate cells (PSCs).METHODS: PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. STAT-specific binding activity was assessed by electrophoretic mobility shift assay. Activation of Src, JAK2,STAT1, STAT3, and ERK was determined by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2′***: PDGF-BB induced STAT-specific binding activity, and activation of Src, JAK2, STAT1, STAT3, and ERK. Ethanol and acetaldehyde at clinically relevant concentrations decreased basal activation of JAK2 and STAT3. PDGFinduced activation of STAT1 and STAT3 was inhibited bya Src inhibitor PP1 and a JAK2 inhibitor AG490, whereasPDGF-induced activation of ERK was inhibited by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and AG490 as well as by STAT3 antisense ***: PDGF-BB activated JAK2-STAT pathwayvia Src-dependent mechanism. Activation of JAK2-STAT3pathway, in addition to ERK, may play a role in PDGF-induced proliferation of PSCs.

关键词： JAK-STAT 酶活性血小板生长因子细胞增殖胰腺星形细胞

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Establishment and characterization of a rat pancreatic stellate cell line by spontaneous immortalization

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World Journal of Gastroenterology 2003年第12期9卷 2751-2758页

作者： Atsushi Masamune Masahiro Satoh kazuhiro kikuta Noriaki Suzuki Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of MedicineSendaiJapan A.M.and M.S.equally contributed to this work

AIM: Activated pancreatic stellate cells (PSCs) have been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line may therefore be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish a cell line of rat PSCs by spontaneous ***: PSCs were isolated from the pancreas of male Wistar rats, and conventional subcultivation was performed repeatedly. Telomerase activity was measured using the telomere repeat amplification protocol. Activation of transcription factors was assessed by electrophoretic mobility shift *** of mitogen-activated protein (MAP) kinases was examined by Western blotting using anti-phosphospecific antibodies. Expression of cytokine-induced neutrophil chemoattractant-1 was determined by enzyme ***: Conventional subcultivation yielded actively growing cells. One clone was obtained after limiting dilution,and designated as SIPS. This cell line has been passaged repeatedly more than 2 years, and is thus likely *** cells retained morphological characteristics of primary,culture-activated PSCs. SIPS expressed α-smooth muscle actin, glial acidic fibrillary protein, vimentin, desmin, type Ⅰ collagen, fibronectin, and prolyl hydroxylases. Telomerase activity and p53 expression were negative. Proliferation of SIPS cells was serum-dependent, and stimulated with platelet-derived growth factor-BB through the activation of extracellular signal-regulated kinase. Interleukin-1β activated nuclear factor-κB, activator protein-1, and MAP ***-1β induced cytokine-induced neutrophil chemoattractant-1 expression through the activation of nuclear factor-κB and MAP ***: SIPS cells can be useful for in vitro studies of cell biology and signal transduction of PSCs.

关键词：胰腺星形细胞胰腺纤维化胰腺炎发病机制自发性无限增殖

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Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation and migration of rat pancreatic stellate cells

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World Journal of Gastroenterology 2005年第22期11卷 3368-3374页

作者： Atsushi Masamune kazuhiro kikuta Masahiro Satoh Noriaki Suzuki Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine Sendai Japan

AIM: To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet-derived growth factor (PDGF)-BBinduced proliferation and migration of pancreatic stellate cells (PSCs).METHODS: PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Cell migration was assessed using modified Boyden chambers. CyclinD1, p21waf1, and p27kip1 expression and phosphorylation of PDGF β-receptor, extracellular signal-regulated kinase, and Akt were examined by Western blotting. Activation of phosphatidylinositol 3-kinase was examined by kinase assay using phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry after staining with propidium iodide. RESULTS: EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyondthe G1 phase, decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF β-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/ Akt ***: EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibrdon of PDGF-mediated signaling pathways.

关键词：绿茶多酚 EGCG PDGF 细胞增殖小鼠动物实验胰腺星形细胞

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Endothelin-1 stimulates contraction and migration of rat pancreatic stellate cells

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World Journal of Gastroenterology 2005年第39期11卷 6144-6151页

作者： Atsushi Masamune Masahiro Satoh kazuhiro kikuta Noriaki Suzuki Kennichi Satoh Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine SendaiJapan

AIM: To examine the ability of ET-1 to affect the cell functions of PSCs and the underlying molecular ***: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, and cells between passages two and five were used. Expression of ET-1 and ET receptors was assessed by reverse transcription-PCR and immunostaining. Phosphorylation of myosin regulatory light chain (MLC), extracellular-signal regulated kinase (ERK), and Akt was examined by Western blotting. Contraction of PSCs was assessed on hydrated collagen lattices. Cell migration was examined using modified Boyden chambers. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-***: Culture-activated PSCs expressed ETA and ETB receptors, and ET-1. ET-1 induced phosphorylation of MLC and ERK, but not Akt. ET-1 induced contraction and migration,but did not alter proliferation of PSCs. ET-1-induced contraction was inhibited by an ETA receptor antagonist BQ-123 and an ETB receptor antagonist BQ-788, whereas migration was inhibited by BQ-788 but not by BQ-123. A Rho kinase inhibitor Y-27632 abolished both contraction and ***: ET-1 induced contraction and migration of PSCs through ET receptors and activation of Rho-Rho kinase. ETA and ETB receptors play different roles in the regulation of these cellular functions in response to ET-1.

关键词：胰腺移植星形细胞细胞功能激酶

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World Journal of Gastroenterology 2015年第33期21卷 9808-9816页

作者： Eriko Nakano Atsushi Kanno Atsushi Masamune Naoki Yoshida Seiji Hongo Shin Miura Tetsuya Takikawa Shin Hamada Kiyoshi Kume kazuhiro kikuta Morihisa Hirota Keisuke Nakayama Fumiyoshi Fujishima Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine Division of Nephrology Endocrinology and Vascular MedicineTohoku University Graduate School of Medicine Department of Pathology Tohoku University Graduate School of Medicine

A 50-year-old male was referred to our hospital for the evaluation of *** positron emission tomography revealed high fluorodeoxyglucose uptake in the pancreas,bilateral lacrimal glands,submandibular glands,parotid glands,bilateral pulmonary hilar lymph nodes,and *** data showed an elevation of hepatobiliary enzymes,renal dysfunction,and remarkably high immunoglobulin(Ig) G levels,without elevated serum *** computed tomography revealed swelling of the pancreatic head and bilateral *** retrograde cholangiopancreatography showed an irregular narrowing of the main pancreatic duct in the pancreatic head and stricture of the lower common bile *** examination by endoscopic ultrasonography-guided fine-needle aspiration revealed findings of lymphoplasmacytic sclerosing pancreatitis without IgG4-positive plasma *** laboratory values and the swelling of several organs were improved by the treatment with *** patient was diagnosed as having type 1 autoimmune pancreatitis(AIP) based on the International Consensus Diagnostic ***,we encountered a case of compatible type 1 AIP without elevated levels of serum IgG4 or IgG4-positive plasma *** case suggests that AIP phenotypes are not always associated with IgG4.

关键词： IgG4-related disease Steroid Intestinal nephritis

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Pancreatic duct drainage using EUS-guided rendezvous technique for stenotic pancreaticojejunostomy

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World Journal of Gastroenterology 2013年第31期19卷 5182-5186页

作者： Tetsuya Takikawa Atsushi Kanno Atsushi Masamune Shin Hamada Eriko Nakano Shin Miura Hiroyuki Ariga Jun Unno Kiyoshi Kume kazuhiro kikuta Morihisa Hirota Hiroshi Yoshida Yu Katayose Michiaki Unno Tooru Shimosegawa Division of Gastroenterology Tohoku University Graduate School of Medicine Miyagi 980-8574 Japan Division of Hepato-biliary-Pancreatic Surgery Tohoku University Graduate School of Medicine Miyagi 980-8574 Japan

The patient was a 30-year-old female who had undergone excision of the extrahepatic bile duct and Rouxen-Y hepaticojejunostomy for congenital biliary dilatation at the age of ***,she suffered from recurrent acute pancreatitis due to pancreaticobiliary maljunction and received subtotal stomach-preserving *** developed a pancreatic fistula and an intra-abdominal abscess after the *** complications were improved by percutaneous abscess drainage and antibiotic *** ever,upper abdominal discomfort and the elevation of serum pancreatic enzymes persisted due to stenosis from the *** we could not accomplish dilation of the stenosis by endoscopic retrograde cholangiopancreatography,we tried an endoscopic ultrasonography(EUS) guided rendezvous technique for pancreatic duct *** transgastric puncture of the pancreatic duct using an EUS-fine needle aspiration needle,the guidewire was inserted into the pancreatic duct and finally reached to the jejunum through the stenotic *** changed the echoendoscope to an oblique-viewing endoscope,then grasped the guidewire and withdrew it through the *** stenosis of the pancreaticojejunostomy was dilated up to 4 mm,and a pancreatic stent was put in *** the pancreatic stent was removed after three months,the patient remained *** duct drainage using an EUS-guided rendezvous technique was useful for the treatment of a stenotic pancreaticojejunostomy after pancreaticoduodenectomy.

关键词： Balloon dilatation Endoscopic ultrasoundguided fine needle aspiration Pancreaticobiliary maljunction Pancreaticoduodenectomy Pancreatitis Postoperative complication

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