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Human Pancreas (human + pancreas)
Selected AbstractsExpression Pattern, Ethanol-Metabolizing Activities, and Cellular Localization of Alcohol and Aldehyde Dehydrogenases in Human Pancreas: Implications for Pathogenesis of Alcohol-Induced Pancreatic InjuryALCOHOLISM, Issue 6 2009Chien-Ping Chiang Background:, Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are major enzymes responsible for metabolism of ethanol. Genetic polymorphisms of ADH1B, ADH1C, and ALDH2 occur among racial populations. The metabolic effect and metabolites contribute to pathogenesis of pancreatic injury. The goal of this study was to determine the functional expressions and cellular localization of ADH and ALDH families in human pancreas. Methods:, Fifty five surgical specimens of normal pancreas as well as 15 samples each for chronic pancreatitis and pancreatic cancer from archival formalin-fixed paraffin-embedded tissue specimens were investigated. Class-specific antibodies were prepared by affinity chromatographies from rabbit antisera raised against recombinant human ADH1C1, ADH4, ADH5, ADH7, ALDH1A1, ALDH2, and ALDH3A1. The isozyme expression patterns of ADH/ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting, and the cellular localizations were detected by immunohistochemistry and histochemistry. Results:, At 33 mM ethanol, pH 7.5, the activities were significantly different between allelic phenotypes of ADH1B. The activity of ALDH2-inactive phenotypes was slightly lower than ALDH2-active phenotypes at 200 ,M acetaldehyde. The protein contents were in the following decreasing order: ALDH1A1, ALDH2, ADH1, and ADH5. ADH1B was detected in the acinar cells and ADH1C in the ductular, islet, and stellate cells. The expression of ADH1C appeared to be increased in the activated pancreatic stellate cells in chronic pancreatitis and pancreatic cancer. Conclusions:, Alcohol dehydrogenase and ALDH family members are differentially expressed in the various cell types of pancreas. ADH1C may play an important role in modulation of activation of pancreatic stellate cells. [source] Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell linesDEVELOPMENTAL DYNAMICS, Issue 8 2008Sonja K. Nielsen Abstract Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis. Developmental Dynamics 237:2039,2052, 2008. © 2008 Wiley-Liss, Inc. [source] VMAT2 quantitation by PET as a biomarker for ,-cell mass in health and diseaseDIABETES OBESITY & METABOLISM, Issue 2008M. Freeby The common pathology underlying both type 1 and type 2 diabetes (T1DM and T2DM) is insufficient ,-cell mass (BCM) to meet metabolic demands. An important impediment to the more rapid evaluation of interventions for both T1DM and T2DM lack of biomarkers of pancreatic BCM. A reliable means of monitoring the mass and/or function of ,-cells would enable evaluation of the progression of diabetes as well as the monitoring of pharmacologic and other interventions. Recently, we identified a biomarker of BCM that is quantifiable by positron emission tomography (PET). PET is an imaging technique which allows for non-invasive measurements of radioligand uptake and clearance, is sensitive in the pico- to nanomolar range and of which the results can be deconvoluted into measurements of receptor concentration. For BCM estimates, we have identified VMAT2 (vesicular monoamine transporter type 2) as a biomarker and [11C] DTBZ (dihydrotetrabenazine) as the transporter's ligand. VMAT2 is highly expressed in ,-cells of the human pancreas relative to other cells of the endocrine and exocrine pancreas. Thus measurements of [11C] DTBZ in the pancreas provide an indirect measurement of BCM. Here we summarize our ongoing efforts to validate the clinical utility of this non-invasive approach to real-time BCM measurements [source] Glucose-Responsive Bioinorganic Nanohybrid Membrane for Self-Regulated Insulin ReleaseADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Claudia R. Gordijo Abstract A bioinorganic nanohybrid glucose-responsive membrane is developed for self-regulated insulin delivery analogous to a healthy human pancreas. The application of MnO2 nanoparticles as a multifunctional component in a glucose-responsive, protein-based membrane with embedded pH-responsive hydrogel nanoparticles is proposed. The bio-nanohybrid membrane is prepared by crosslinking bovine serum albumin (BSA),MnO2 nanoparticle conjugates with glucose oxidase and catalase in the presence of poly(N -isopropyl acrylamide- co -methacrylic acid) nanoparticles. The preparation and performance of this new nanocomposite material for a glucose-responsive insulin release system is presented. The activity and stability of immobilized glucose oxidase and the morphology and mechanical properties of the membrane are investigated. The enzymatic activity is well preserved in the membranes. The use of MnO2 nanoparticles not only reinforces the mechanical strength and the porous structure of the BSA-based membrane, but enhances the long-term stability of the enzymes. The in vitro release of insulin across the membrane is modulated by changes in glucose concentration mimicking possible fluctuations of blood-glucose level in diabetic patients. A four-fold increase in insulin permeation is observed when the glucose concentration is increased from normal to hyperglycemic levels, which returns to the baseline level when the glucose concentration is reduced to a normal level. [source] Expression Pattern, Ethanol-Metabolizing Activities, and Cellular Localization of Alcohol and Aldehyde Dehydrogenases in Human Pancreas: Implications for Pathogenesis of Alcohol-Induced Pancreatic InjuryALCOHOLISM, Issue 6 2009Chien-Ping Chiang Background:, Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are major enzymes responsible for metabolism of ethanol. Genetic polymorphisms of ADH1B, ADH1C, and ALDH2 occur among racial populations. The metabolic effect and metabolites contribute to pathogenesis of pancreatic injury. The goal of this study was to determine the functional expressions and cellular localization of ADH and ALDH families in human pancreas. Methods:, Fifty five surgical specimens of normal pancreas as well as 15 samples each for chronic pancreatitis and pancreatic cancer from archival formalin-fixed paraffin-embedded tissue specimens were investigated. Class-specific antibodies were prepared by affinity chromatographies from rabbit antisera raised against recombinant human ADH1C1, ADH4, ADH5, ADH7, ALDH1A1, ALDH2, and ALDH3A1. The isozyme expression patterns of ADH/ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting, and the cellular localizations were detected by immunohistochemistry and histochemistry. Results:, At 33 mM ethanol, pH 7.5, the activities were significantly different between allelic phenotypes of ADH1B. The activity of ALDH2-inactive phenotypes was slightly lower than ALDH2-active phenotypes at 200 ,M acetaldehyde. The protein contents were in the following decreasing order: ALDH1A1, ALDH2, ADH1, and ADH5. ADH1B was detected in the acinar cells and ADH1C in the ductular, islet, and stellate cells. The expression of ADH1C appeared to be increased in the activated pancreatic stellate cells in chronic pancreatitis and pancreatic cancer. Conclusions:, Alcohol dehydrogenase and ALDH family members are differentially expressed in the various cell types of pancreas. ADH1C may play an important role in modulation of activation of pancreatic stellate cells. [source] | ||||||||||