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Zhang Yifan - - 2012
Glucagon-like peptide-1 (GLP-1) is a potent antihyperglycemic hormone. It can induce glucose-dependent insulin secretion. GLP-1 has a short half-life of less than 2 min in vivo due to degradation by the dipeptidyl peptidase-IV. GLP-l analogues, such as exendin-4 and exendin-3, have similar biological activity but a longer in-vivo half-life. Pancreatic ...
Zhao Ling - - 2012
Tumor suppressor gene Ras-association domain family 2A (RASSF2A) is inactivated by promoter hypermethylation in many cancers. The study was performed to evaluate the methylation status of RASSF2A in pancreatic ductal adenocarcinoma and cell lines and its relation to clinicopathologic features. The RASSF2 expression in 8 pancreatic carcinoma cell lines and ...
Keefe Matthew D - - 2012
The size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth and are capable of at least ...
Gallo R - - 2012
Post-transplant diabetes mellitus represents an important complication of prolonged immunosuppressive treatment after solid organ transplantation. The immunosuppressive toxicity, responsible for a persistent impairment of glucose metabolism in pancreatic islet-transplanted patients, is mainly attributed to calcineurin inhibitors and steroids, while other immunosuppressive molecules (azathioprine and mycophenolic acid, MPA) are considered not ...
Chetboun Moria - - 2012
Whereas oxidative stress is linked to cellular damage, reactive oxygen species (ROS) are also believed to be involved in the propagation of signaling pathways. Studies on the role of ROS in pancreatic beta-cell physiology, in contrast to pathophysiology, have not yet been reported. In this study we investigate the importance ...
Iglesias Itzia - - 2012
The choice of enzyme blend is critical for successful islet isolation. Islet yield, viability, integrity, and function are important factors that influence the outcome of islet transplantation. Liberase HI has been used as a standard enzyme for pancreas digestion and has successfully produced islets that reversed diabetes. However, the replacement ...
Shields Mario A - - 2012
The Snail family of transcription factors has been implicated in pancreatic cancer progression. We recently showed that Snail (Snai1) promotes membrane-type 1 matrix metalloproteinase (MT1-MMP)- and ERK1/2-dependent scattering of pancreatic cancer cells in three-dimensional type I collagen. In this study, we examine the role of Slug (Snai2) in regulating pancreatic ...
Chung Yeon Tae - - 2012
Aldo-keto reductase family 1B10 (AKR1B10) exhibits more restricted lipid substrate specificity (including farnesal, geranylgeranial, retinal and carbonyls), and metabolizing these lipid substrates has a crucial role in promoting carcinogenesis. Overexpression of AKR1B10 has been identified in smoking-related carcinomas such as lung cancer. As development of pancreatic cancer is firmly linked ...
Kobayashi Masaki - - 2012
Diabetes is characterized by an absolute or relative deficiency of pancreatic β-cells. New strategies to accelerate β-cell neogenesis or maintain existing β-cells are desired for future therapies against diabetes. We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. However, we also reported that FoxO1 ...
Miki Rika - - 2011
The origins of liver progenitor cells have been extensively studied, but evidence on the origin of pancreatic precursor cells is currently limited. Pancreatic and duodenal homeobox gene 1 (Pdx1) is one of the earliest known markers for the pancreas. A transgenic mouse line expressing green fluorescent protein (GFP) under the ...
Rachdi Latif - - 2012
Leucine (Leu) is an essential branched-chain amino acid, which activates the mammalian target of rapamycin (mTOR) signaling pathway. The effect of Leu on cell differentiation during embryonic development is unknown. Here, we show that Leu supplementation during pregnancy significantly increased fetal body weight, caused fetal hyperglycemia and hypoinsulinemia, and decreased ...
Saito Rie - - 2011
Activin A is a differentiation factor for β-cells and is effective to promote β-cell neogenesis. Activin A is also an autocrine activator of pancreatic stellate cells, which play a critical role in fibrogenesis of the pancreas. Conophylline (CnP) is a natural compound, which reproduces the effect of activin on β-cell ...
Walter Robert J - - 2012
Context Pancreatic cancer is highly resistant to treatment. Previously, we showed that Newcastle disease virus (NDV) strain 73-T was highly cytotoxic to a range of tumor types in vitro and in vivo but the effects of NDV on pancreatic tumors are unknown. We determined the cytotoxicity of the lentogenic LaSota ...
Subramanian Veedamali S - - 2012
Thiamin is essential for normal function of pancreatic acinar cells, and its deficiency leads to a reduction in pancreatic digestive enzymes. We have recently shown that thiamin uptake by rat pancreatic acinar cells is carrier-mediated and that both thiamin transporter (THTR)-1 and THTR-2 are expressed in these cells; little, however, ...
Kawanami Takako - - 2012
Pancreatic cancer is a disease with a dismal prognosis and treatment options are limited. This study investigated the interaction of gemcitabine with R1507 and/or metformin and the induction of an inhibitor of apoptosis protein by this com-bination. Pancreatic cancer cells were treated with gemcitabine, R1507 and metformin alone or in ...
Magzoub Mazin - - 2012
Islet amyloid polypeptide (IAPP) is a peptide hormone cosecreted with insulin by pancreatic β-cells. In type II diabetes, IAPP aggregates in a process that is associated with β-cell dysfunction and loss of β-cell mass. The relationship between IAPP's conformational landscape and its capacity to mediate cell death remains poorly understood. ...
Ziolkowski Andrew F - - 2012
The autoimmune type 1 diabetes (T1D) that arises spontaneously in NOD mice is considered to be a model of T1D in humans. It is characterized by the invasion of pancreatic islets by mononuclear cells (MNCs), which ultimately leads to destruction of insulin-producing β cells. Although T cell dependent, the molecular ...
Westmoreland Joby J - - 2012
The exocrine portion of the pancreas functions in digestion and preserves pancreatic homeostasis. Learning how this tissue forms during embryogenesis could improve our understanding of human pancreatic diseases. Expression of the homeobox gene Prox1 in the exocrine pancreas changes throughout development in mice. We investigated the role of Prox1 in ...
Liu Zhiqing - - 2011
This study examined the expression of cell adhesion molecule 1 (CADM1) in pancreatic cancer and the possible mechanism. The expression of CADM1 was detected by immunohistochemistry in tissues of pancreatic cancer, pancreatitis, and normal pancreas. The plasmid pcDNA3.1-Hygro(+)/CADM1 was transfected into PANC-1 cells (a pancreatic cancer cell line). The expression ...
Reichert Maximilian - - 2011
The pancreas is a complex organ comprised of three critical cell lineages: islet (endocrine), acinar, and ductal. This review will focus upon recent insights and advances in the biology of pancreatic ductal cells. In particular, emphasis will be placed upon the regulation of ductal cells by specific transcriptional factors during ...
Kopinke Daniel - - 2012
The Notch signaling pathway regulates embryonic development of the pancreas, inhibiting progenitor differentiation into exocrine acinar and endocrine islet cells. The adult pancreas appears to lack progenitor cells, and its mature cell types are maintained by the proliferation of pre-existing differentiated cells. Nonetheless, Notch remains active in adult duct and ...
Rajpal Gautam - - 2012
For insulin synthesis, the proinsulin precursor is translated at the endoplasmic reticulum (ER), folds to include its three native disulfide bonds, and is exported to secretory granules for processing and secretion. Protein disulfide isomerase (PDI) has long been assumed to assist proinsulin in this process. Herein we have examined the ...
Klee Philippe - - 2011
Type 1 diabetes develops when most insulin-producing β cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of β cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions ...
Ohashi K - - 2011
To establish novel islet-based therapies, our group has recently developed technologies to create a contiguous, monolayered sheet made from freshly dispersed islet cells. Islet cell sheets generated from freshly isolated cells are easily transplantable for engraftment into subcutaneous sites in rodents. The use of a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), grafted ...
Tehrani Zahra - - 2011
Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic β cells. Current efforts to cure diabetes are aimed at replenishing damaged cells by generating a new supply of β cells in vitro. The most promising strategy for achieving this goal is to differentiate embryonic stem (ES) cells by ...
Lim Sue Mei - - 2011
In order to develop methods for the generation of insulin-producing β-cells for the treatment of diabetes, we have used GFP-tagged ESCs to elucidate the process of pancreas development. Using the reporter Pdx1GFP/w ESC line, we have previously described a serum-free differentiation protocol in which Pdx1-GFP+ cells formed GFP bright epithelial ...
Chu K Y - - 2011
AIMS/HYPOTHESIS: Ubiquitin C-terminal hydrolase L1 (UCHL1) is associated with neurodegenerative diseases and has been suggested to have roles in pancreatic beta cells. Our proteomic analysis revealed that UCHL1 was the most increased protein in MIN6 cells exposed to palmitate. The present study used a genetic loss-of-function model to test the ...
Chung Yuan-Chiang - - 2011
OBJECTIVES:: Grape-seed procyanidins (GSPs) can inhibit cell proliferation and invasiveness in various human cancers. However, the effect of GSP on pancreatic carcinoma cells has not been investigated. METHODS:: Pancreatic carcinoma cell lines MIA PaCa-2 and BxPC-3 treated with GSP were assessed for viability by trypan blue exclusion, for cell cycle ...
Robson-Doucette Christine A - - 2011
The role of uncoupling protein 2 (UCP2) in pancreatic β-cells is highly debated, partly because of the broad tissue distribution of UCP2 and thus limitations of whole-body UCP2 knockout mouse models. To investigate the function of UCP2 in the β-cell, β-cell-specific UCP2 knockout mice (UCP2BKO) were generated and characterized. UCP2BKO ...
Cherubini G - - 2011
Pancreatic adenocarcinomas are aggressive and frequently develop resistance to all current therapies. Replication-selective adenoviruses can overcome resistance to chemotherapeutics through their sensitizing effects on drug-induced cell killing. We previously found that adenovirus deleted in the anti-apoptotic E1B19K gene enhanced gemcitabine-induced apoptotis. Here we demonstrate that our engineered double-deleted AdΔΔ mutant ...
Tanemura M - - 2011
Autophagy is a lysosomal degradation process of redundant or faulty cell components in normal cells. However, certain diseases are associated with dysfunctional autophagy. Rapamycin, a major immunosuppressant used in islet transplantation, is an inhibitor of mammalian target of rapamycin and is known to cause induction of autophagy. The objective of ...
Fendrich Volker - - 2011
Ligand-dependent activation of the Hedgehog (Hh) signaling pathway has been implicated in both tumor initiation and metastasis of pancreatic ductal adenocarcinoma (PDAC). Prior studies in genetically engineered mouse models (GEMMs) have assessed the role of Hh signaling by cell autonomous expression of a constitutively active Gli2 within epithelial cells. On ...
Magenheim Judith - - 2011
How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels ...
Munding Johanna B - - 2011
Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs), considered a new class of biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection ...
Lenoir Olivia - - 2011
Class IIa histone deacetylases (HDACs) belong to a large family of enzymes involved in protein deacetylation and play a role in regulating gene expression and cell differentiation. Previously, we showed that HDAC inhibitors modify the timing and determination of pancreatic cell fate. The aim of this study was to determine ...
Misawa R - - 2012
The selection of enzyme blend is critical for the success of human islet isolations. Liberase HI collagenase (Roche) was introduced in the 1990s and had been widely used for clinical islet transplantation. More recently, a blend collagenase NB1 has been rendered available. The aim of this study was to evaluate ...
Serafimidis Ioannis - - 2011
During development pancreatic endocrine cells migrate in a coordinated fashion. This migration is necessary to form fully functional islets, but the mechanisms involved remain unknown. Therapeutic strategies to restore β-cell mass and islet functionality by reprogramming endogenous exocrine cells would be strengthened from simultaneous treatments that enhance endocrine cell clustering. ...
Nordstoga K - - 2011
In both man and animals, inflammatory changes in the pancreas often occur with disturbances in lipid metabolism, including hypertriglyceridemia and an excess of free fatty acids. Hyperlipoproteinemia type I is a human condition caused by a deficiency of lipoprotein lipase. A similar metabolic disturbance that occurs in mink is of ...
Latsabidze I - - 2011
Using the methods of light and electron microscopy, pancreas was studied in the experimental model (Rats-30) of alloxan diabetes - one month from alloxan injection and after the action of Plaferon LB (amniotic interferon). Special emphasis was made on display of extra-islet cells. Data obtained suggest that extra-islet cells exist ...
Funel Niccola - - 2011
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and molecular studies to unravel novel biomarkers and therapeutic targets are warranted. However, PDAC is characterized by different precursor lesions, as well as by an intense desmoplastic reaction, with islet of neoplastic cells often representing a minor population. Moreover, normal ductal cells, ...
Jakab Cs - - 2011
Aims: Claudins, integral membrane proteins are components of the tight junction structures between epithelial and endothelial cells. These transmembrane proteins create a primary barrier to prevent paracellular transport of solutes, and also restrict the lateral diffusion of membrane lipids and proteins to maintain the cellular polarity. The aim of the ...
Landsman Limor - - 2011
The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating ...
Subramanya Sandeep B - - 2011
Thiamin is important for normal function of pancreatic acinar cells, but little is known about its mechanism of uptake and about the effect of chronic alcohol use on the process. We addressed these issues using freshly isolated rat primary and rat-derived cultured AR42J pancreatic acinar cells as models. Results showed ...
Chung Sung Soo - - 2011
Thiazolidinediones (TZDs) are synthetic ligands of peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear receptor superfamily. TZDs are known to increase insulin sensitivity, and also to have an antioxidative effect. In this study, we tested whether TZDs protect pancreatic β-cells from oxidative stress, and we investigated the mechanism ...
Jo Junghyo - - 2011
The islets of Langerhans, micro-organs for maintaining glucose homeostasis, range in size from small clusters of <10 cells to large islets consisting of several thousand endocrine cells. Islet size distributions among various species are similar and independent of body size, suggesting an intrinsic limit to islet size. Little is known ...
Youos John G - - 2011
Nowadays, most of the basic pancreatic islet research is focused on the beta and alpha cells. Nonetheless, the pancreatic islets are complete organs with five, up to now, different cell types and dedicated vasculature and neural supply. Every cell contributes in the integration of the islet function and deserves a ...
Morris Christina - - 2011
We present here a robust microfluidic cell perifusion device for in vitro primary tissue cell secretion studies. This system increases the sample concentration to perifusion volume ratio by an order of magnitude compared with standard multi-well plate static incubation assays. Further, this device achieves physiologically relevant flow rates, pressures, and ...
Whalley Nicola - - 2011
Proglucagon is cleaved to glucagon by prohormone convertase 2 (PC2) in pancreatic alpha-cells, but is cleaved to GLP-1 by PC1 in intestinal L-cells. The aim of this study was to identify mechanisms which switch processing of proglucagon to generate GLP-1 in the pancreas, given that GLP-1 can increase insulin secretion ...
Chen Hao - - 2011
An unresolved obstacle in transplantation of islets of Langerhans is the early graft loss caused by thrombotic reactions on the surface of islets after intraportal transplantation. We investigated a versatile method for modifying the surface of islets with liposomes carrying the anticoagulant argatroban using an amphiphilic poly(ethylene glycol)-phospholipid conjugate derivative ...
Schwer Christian I - - 2011
OBJECTIVES:: Pancreatic stellate cells (PSCs) play a crucial role during pancreatic fibrosis development. Hydrogen sulfide (H2S) is a recently discovered gaseous transmitter, whose role in PSCs has not been explored yet. In the present study, we examined the effects of sodium hydrosulfide (NaHS), an H2S donor, on rat PSCs and ...
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