Genomes and Genes
Experts and Doctors on pancreas in Ann Arbor, Michigan, United States
Locale: Ann Arbor, Michigan, United States
- Gurda G, Crozier S, Ji B, Ernst S, Logsdon C, Rothermel B, et al. Regulator of calcineurin 1 controls growth plasticity of adult pancreas. Gastroenterology. 2010;139:609-19, 619.e1-6 pubmed publisher..We profile adaptive pancreatic growth, identify Rcan1 as an important new feedback regulator, and firmly establish that CN-NFAT signaling is required for this response. ..
- Sans M, Xie Q, Williams J. Regulation of translation elongation and phosphorylation of eEF2 in rat pancreatic acini. Biochem Biophys Res Commun. 2004;319:144-51 pubmed..Translation elongation in pancreatic acinar cells is likely regulated by eEF2 through the mTOR, p38, and MEK pathways, and modulated through PP2A. ..
- Guo L, Sans M, Gurda G, Lee S, Ernst S, Williams J. Induction of early response genes in trypsin inhibitor-induced pancreatic growth. Am J Physiol Gastrointest Liver Physiol. 2007;292:G667-77 pubmed..These results indicate that camostat feeding induces a spectrum of early response gene expression and AP-1 DNA binding and that these effects are mainly CCK dependent. ..
- Chen X, Ernst S, Williams J. Dominant negative Rab3D mutants reduce GTP-bound endogenous Rab3D in pancreatic acini. J Biol Chem. 2003;278:50053-60 pubmed..6 +/- 3.3%. The two dominant negative Rab3D mutants, therefore, interfere with endogenous Rab3D function by blocking the GDP/GTP exchange but not zymogen granule targeting of endogenous Rab3D. ..
- Wagner A, Strowski M, Williams J. Identification of Rab 5 but not Rab 3A in rat pancreatic zymogen granule membranes. Biochem Biophys Res Commun. 1994;200:542-8 pubmed..Of these, Rab 5 was identified in purified zymogen granule membranes where it may be involved in the endocytotic retrieval of granule membrane following exocytosis. ..
- Wishart M, Andrews P, Nichols R, Blevins G, Logsdon C, Williams J. Identification and cloning of GP-3 from rat pancreatic acinar zymogen granules as a glycosylated membrane-associated lipase. J Biol Chem. 1993;268:10303-11 pubmed..Close homology is observed between GP-3 and a lipase molecule previously isolated from mouse cytotoxic T cells. ..
- Jung G, Louie D, Owyang C. Pancreatic polypeptide inhibits pancreatic enzyme secretion via a cholinergic pathway. Am J Physiol. 1987;253:G706-10 pubmed..This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function...
- O SHEA S, Johnson K, Clark R, Sliwkowski M, Erickson S. Effects of in vivo heregulin beta1 treatment in wild-type and ErbB gene-targeted mice depend on receptor levels and pregnancy. Am J Pathol. 2001;158:1871-80 pubmed..Hyperplasia of other epithelial tissues such as the pancreas and intestine and the growth of cardiac nerve bundles were also observed, independent of sex. ..
- Simeone D, Zhang L, Graziano K, Nicke B, Pham T, Schaefer C, et al. Smad4 mediates activation of mitogen-activated protein kinases by TGF-beta in pancreatic acinar cells. Am J Physiol Cell Physiol. 2001;281:C311-9 pubmed..These studies provide new insight into the signaling mechanisms by which TGF-beta mediates biological actions in pancreatic acinar cells...
- Ji B, Chen X, Misek D, Kuick R, Hanash S, Ernst S, et al. Pancreatic gene expression during the initiation of acute pancreatitis: identification of EGR-1 as a key regulator. Physiol Genomics. 2003;14:59-72 pubmed..Thus this study identified EGR-1 and several other novel genes likely to be important in the development and severity of acute pancreatitis. ..
- Keller S, Rosenberg M, Johnson T, Howard G, Meisler M. Regulation of amylase gene expression in diabetic mice is mediated by a cis-acting upstream element close to the pancreas-specific enhancer. Genes Dev. 1990;4:1316-21 pubmed..The data presented here demonstrate that the 5'-flanking region of the pancreatic amylase gene contains a novel insulin-dependent element (IDE) that mediates the loss of expression in diabetic animals. ..
- Zhang L, Duan C, Binkley C, Li G, Uhler M, Logsdon C, et al. A transforming growth factor beta-induced Smad3/Smad4 complex directly activates protein kinase A. Mol Cell Biol. 2004;24:2169-80 pubmed..Taken together, these data indicate an important and previously unrecognized interaction between the TGFbeta and PKA signaling pathways. ..
- Li C, Chen X, Williams J. Regulation of CCK-induced amylase release by PKC-delta in rat pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol. 2004;287:G764-71 pubmed..These results indicate that PKC-delta is the PKC isoform involved with amylase secretion. ..
- Okami J, Simeone D, Logsdon C. Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer. Cancer Res. 2004;64:5338-46 pubmed..In conclusion, down-regulation of BNIP3 by CpG methylation likely contributes to resistance to hypoxia-induced cell death in pancreatic cancer. ..
- Pausawasdi N, Heidt D, Kwon R, Simeone D, Scheiman J. Long-term follow-up of patients with incidentally discovered pancreatic cystic neoplasms evaluated by endoscopic ultrasound. Surgery. 2010;147:13-20 pubmed publisher..Asymptomatic cysts with benign radiographic and/or endosonographic features may safely be followed clinically and with serial imaging. ..
- Fajans S, Bell G, Paz V, Below J, Cox N, Martin C, et al. Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60. Transl Res. 2010;156:7-14 pubmed publisher..Genetic testing should be considered in multigenerational obese diabetic subjects, particularly when such families contain young diabetic members. ..
- Ku N, Toivola D, Strnad P, Omary M. Cytoskeletal keratin glycosylation protects epithelial tissue from injury. Nat Cell Biol. 2010;12:876-85 pubmed publisher..Therefore, K18 glycosylation provides a unique protective role in epithelial injury by promoting the phosphorylation and activation of cell-survival kinases...
- DiMagno M, Hao Y, Tsunoda Y, Williams J, Owyang C. Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in mice. Am J Physiol Gastrointest Liver Physiol. 2004;286:G428-36 pubmed..eNOS likely plays a dominant role, because eNOS deletion mimics NOS blockade by inhibiting CCK-8 and carbachol-stimulated secretion, whereas nNOS deletion augments CCK-8 but not carbachol-stimulated secretion. ..
- Flowe K, Lally K, Mulholland M. Galanin inhibits rat pancreatic amylase release via cholinergic suppression. Peptides. 1992;13:487-92 pubmed..1 +/- 0.6% vs. 7.3 +/- 0.4%). Veratridine-stimulated (10(-4) M) amylase secretion and ACh release (12.4 +/- 1.7% vs. 8.5 +/- 0.7%) were similarly diminished...
- Duan R, Zheng C, Guan K, Williams J. Activation of MAP kinase kinase (MEK) and Ras by cholecystokinin in rat pancreatic acini. Am J Physiol. 1995;268:G1060-5 pubmed..In conclusion, the activation of MAP kinase by CCK can be explained by activation of MEK and may involve the activation of Ras by a protein kinase C-dependent mechanism...
- Li Y, Hao Y, Owyang C. Diazepam-binding inhibitor mediates feedback regulation of pancreatic secretion and postprandial release of cholecystokinin. J Clin Invest. 2000;105:351-9 pubmed..Hence, DBI, a trypsin-sensitive CCK-RP secreted from the proximal small bowel, mediates the feedback regulation of pancreatic secretion and the postprandial release of CCK. ..
- Li Y, Wu X, Zhu J, Owyang C. Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors. Am J Physiol Gastrointest Liver Physiol. 2001;281:G916-23 pubmed..In this manner, 5-HT acts as a paracrine substance to stimulate pancreatic secretion via a vagal cholinergic pathway...
- Chen X, Edwards J, Logsdon C, Ernst S, Williams J. Dominant negative Rab3D inhibits amylase release from mouse pancreatic acini. J Biol Chem. 2002;277:18002-9 pubmed..These results suggest that Rab3D plays an important role in regulating the terminal steps of acinar exocytosis and that this effect is greatest on the early phase of amylase release. ..
- Guzman E, Zhang W, Lin T, Mulholland M. Stimulation of rat pancreatic exocrine secretion by urocortin and corticotropin releasing factor. Peptides. 2003;24:727-34 pubmed..In acinar cells, UCN did not stimulate release of amylase nor intracellular cAMP. UCN is a pancreatic exocrine secreatagogue with effects mediated through cholinergic intrapancreatic neurons. ..
- Sans M, Kimball S, Williams J. Effect of CCK and intracellular calcium to regulate eIF2B and protein synthesis in rat pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol. 2002;282:G267-76 pubmed
- Chen X, Li C, Izumi T, Ernst S, Andrews P, Williams J. Rab27b localizes to zymogen granules and regulates pancreatic acinar exocytosis. Biochem Biophys Res Commun. 2004;323:1157-62 pubmed..This enhancement and inhibition occurred at all points on the CCK dose-response curve and over a 30min time course. These results demonstrate that Rab27b is present on ZGs and plays an important role in regulating acinar exocytosis. ..
- Sans M, Lee S, D Alecy L, Williams J. Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA. Am J Physiol Gastrointest Liver Physiol. 2004;287:G667-75 pubmed..By contrast, feeding did not affect eIF2B activity. Thus food intake stimulates pancreatic protein synthesis and translational effectors without increasing digestive enzyme mRNA levels. ..
- Lacourse K, Swanberg L, Gillespie P, Rehfeld J, Saunders T, Samuelson L. Pancreatic function in CCK-deficient mice: adaptation to dietary protein does not require CCK. Am J Physiol. 1999;276:G1302-9 pubmed..Altered somatostatin concentrations in brain and duodenum of CCK-deficient mice suggest that other regulatory pathways are modified to compensate for the CCK deficiency. ..
- Chen X, Sans M, Strahler J, Karnovsky A, Ernst S, Michailidis G, et al. Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreas. J Proteome Res. 2010;9:885-96 pubmed publisher..These results suggest that the early stages of AP involve changes of multiple RER proteins that may affect the synthesis and processing of digestive enzymes. ..
- Dickinson C, Delvalle J, Todisco A, Gantz I, Tong L, Finniss S, et al. Canine prosomatostatin: isolation of a cDNA, regulation of gene expression, and characterization of post-translational processing intermediates. Regul Pept. 1996;67:145-52 pubmed..Furthermore, equivalent amounts of SS-14 and SS-28(1-12) were co-released from canine fundic D-cells by CCK (10(-8) M) suggesting that the generation of these products occurs within the same regulated pathway of secretion. ..
- Sans M, Williams J. Calcineurin is required for translational control of protein synthesis in rat pancreatic acini. Am J Physiol Cell Physiol. 2004;287:C310-9 pubmed..From these results, we conclude that calcineurin activity is required for protein synthesis, and this action may be related to an effect on the formation of the mRNA cap binding complex and the elongation processes. ..
- Groblewski G, Wagner A, Williams J. Cyclosporin A inhibits Ca2+/calmodulin-dependent protein phosphatase and secretion in pancreatic acinar cells. J Biol Chem. 1994;269:15111-7 pubmed..Collectively, these data indicate that the Ca2+/calmodulin-dependent protein phosphatase, PP2B, plays a significant role in stimulus-secretion coupling in pancreatic acinar cells. ..
- Samuelson L, Wiebauer K, Howard G, Schmid R, Koeplin D, Meisler M. Isolation of the murine ribonuclease gene Rib-1: structure and tissue specific expression in pancreas and parotid gland. Nucleic Acids Res. 1991;19:6935-41 pubmed..This is in contrast with the mechanism for production of amylase in pancreas and parotid, which is accomplished by tissue specific expression of different gene copies. ..
- Zhu J, He J, Liu Y, Simeone D, Lubman D. Identification of glycoprotein markers for pancreatic cancer CD24+CD44+ stem-like cells using nano-LC-MS/MS and tissue microarray. J Proteome Res. 2012;11:2272-81 pubmed publisher..Our findings suggest that these glycoproteins may provide potential therapeutic targets and promising prognostic markers for pancreatic cancer. ..
- DiMagno M, Williams J, Hao Y, Ernst S, Owyang C. Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in mice. Am J Physiol Gastrointest Liver Physiol. 2004;287:G80-7 pubmed..Thus eNOS is the main isoform influencing the initiation of caerulein-induced AP. eNOS-derived NO exerts a protective effect through actions on nonacinar cell types, most likely endothelial cells, to produce greater PMBF. ..
- Samuelson L, Wiebauer K, Gumucio D, Meisler M. Expression of the human amylase genes: recent origin of a salivary amylase promoter from an actin pseudogene. Nucleic Acids Res. 1988;16:8261-76 pubmed..In addition, insertion of an endogenous retrovirus has interrupted the gamma-actin pseudogene in four of the five amylase genes. ..
- Sabbatini M, D ALECY L, Lentz S, Tang T, Williams J. Adenylyl cyclase 6 mediates the action of cyclic AMP-dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation. J Physiol. 2013;591:3693-707 pubmed publisher..In conclusion, several AC isoforms are expressed in pancreatic acini and ducts. AC6 mediates a significant part of pancreatic amylase and fluid secretion in response to secretin, VIP and forskolin through cAMP/PKA pathway activation. ..