Disease relevance of Pan1

• In both of these studies we observed the disappearance from the pancreas of the insulin-producing beta cells coinciding with the development of insulin-dependent diabetes mellitus [1].
• The pancreas shows progressive interstitial fibrosis and a florid acinoductular metaplasia, during which acinar cells appear to degranulate, dedifferentiate, and assume characteristics of intercalated or centroacinar duct cells [2].
• To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas [3].
• Isolation of a virus from the pancreas of a child with diabetic ketoacidosis [4].
• Objective responses were evident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (skin, soft tissue, lung, pancreas) and one additional minor response [5].

Psychiatry related information on Pan1

• Huntington's disease of the endocrine pancreas: insulin deficiency and diabetes mellitus due to impaired insulin gene expression [6].
• Previous reports have provided suggestive evidence for a role of endogenous opiates in modulating feeding behavior as well as insulin secretion from the pancreas [7].
• Four months of alcohol consumption did not result in apparent morphological changes of the pancreas [8].
• The effect of L-buthionine-[S,R]-sulfoximine on the pancreas in mice. A model of weakening glutathione-based defense mechanisms [9].

High impact information on Pan1

• OT receptors have also been identified in other tissues, including the kidney, heart, thymus, pancreas, and adipocytes [10].
• The absence of a major transcript in the pancreas and thyroid (deletions from both families) and an eye-specific transcript (deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals [11].
• However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear [12].
• In this issue of Cell, propose that a defect in a subset of sensory neurons innervating the pancreas plays a major role in initiating the chain of events that will lead to local inflammation, islet destruction, and autoimmune diabetes [13].
• Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks [12].

Chemical compound and disease context of Pan1

• The effects of starvation and refeeding and of obesity on pancreatic alpha2- and beta-cell responses to glucose or tolbutamide were studied with the isolated rat or mouse pancreas perfused with an amino acid mixture in the presence and absence of glucose [14].
• These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation of the pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis [15].
• Luminal bile salts appear to provide a physiologic protection against necrotizing pancreatitis, at least in part, both by inhibiting the release of CCK and by promoting resistance of the pancreas to CCK excessive stimulation in vivo [16].
• These studies demonstrate a protective effect of prostaglandin on the pancreas and suggest a role for endogenous prostaglandins in the pathophysiology of pancreatitis [17].
• We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis [18].

Biological context of Pan1

• Given the essential role of IPF1 in pancreas development, it is likely that this autosomal recessive mutation is the cause of the pancreatic agenesis phenotype in this patient [19].
• The timing of cyst formation indicates that full-length polycystin is required for normal morphogenesis during elongation and maturation of tubular structures in the kidney and pancreas [20].
• Glut-2 is thus required to maintain normal glucose homeostasis and normal function and development of the endocrine pancreas [21].
• We show that microinjection of a construct in which the elastase I promoter/enhancer is fused to a gene for diphtheria toxin A polypeptide results in birth of mice lacking a normal pancreas because of expression of the toxin in pancreatic acinar cells [22].
• Second, in pancreas it promoted proliferation of both acinar cells and fibroblasts and focally altered acinar cell differentiation [23].

Anatomical context of Pan1

• The remnant Hlxb9-/- pancreas has small islets of Langerhans with reduced numbers of insulin-producing beta-cells [24].
• The 1577 and 1659 nucleotide mRNAs from pancreas and salivary gland, respectively are the major alpha-amylase species which accumulate in each tissue [25].
• They were also found in homogenates of other rat tissues, including pancreas, heart, brain, kidney, stomach, and adrenal gland, but not in lens fiber material [26].
• In most mammals the pancreas develops from the foregut endoderm as ventral and dorsal buds [24].
• TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas [2].

Associations of Pan1 with chemical compounds

• Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses [27].
• In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant [28].
• In the pancreas from animals starved for 3 d, glucose and tolbutamide suppression of alpha2-cells took place in the absence of demonstrable changes of insulin release [14].
• Morphometric analysis verified a six-fold increase in beta cell mass/pancreas, a two-fold increase in 5-bromo-2'-deoxyuridine incorporation, a four-fold increase in the number of beta cells per pancreas area, and a two-fold increase in cell size in transgenic compared with wild-type mice at 5 weeks [29].
• Similarly, PGE2 (0.10 microgram/g body wt) diminished the magnitude of the increase in in-vitro protein discharge and the elevated concentrations of trypsinogen and chymotrypsinogen in pancreas fragments taken from mice given the CDE diet [30].

Physical interactions of Pan1

• Hepatocyte nuclear factors (HNFs) -1alpha, -3beta, -4alpha, and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in beta-cell development and function [31].
• Given its wide tissue distribution, CFEX also may contribute to transcellular Cl(-) transport in additional epithelia such as the pancreas and contribute to transmembrane Cl(-) transport in nonepithelial tissues such as the heart [32].
• Immunohistological studies of native and grafted rat pancreas tissue with mouse anti-rat monoclonal antibodies revealed an unexpected staining pattern of MRC Ox 39 which binds specifically to rat interleukin-2 (IL-2) receptors [33].
• Cytokines have been regarded as effector molecules responsible for beta-cell death and major histocompatibility complex hyperexpression in endocrine pancreas of type I diabetes [34].
• No saturable gastrin binding to normal nontransgenic mouse pancreas was found [35].

Enzymatic interactions of Pan1

• Hepatocyte nuclear factor 6 (HNF-6) belongs to the family of One Cut transcription factors (also known as OC-1) and is essential for the development of the mouse pancreas, gall bladder, and the interhepatic bile ducts [36].

Regulatory relationships of Pan1

• The Pax4 gene is expressed in the early pancreas, but is later restricted to beta cells [37].
• Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas [38].
• However, embryos lacking Ngn3 fail to express IA1 in the pancreas [39].
• Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a [40].
• Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development [41].

Other interactions of Pan1

• Thus, Hlxb9 is key to normal pancreas development and function [24].
• We now show that mice homozygous for a targeted mutation in the Ipf1 gene selectively lack a pancreas [42].
• Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas [43].
• The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas [37].
• Here, to test this idea, we analysed pancreas development in mice genetically altered at several steps in the Notch signalling pathway [44].

Analytical, diagnostic and therapeutic context of Pan1

• Localization of antibody binding in pancreas was similar to that of liver, while in heart ventricle the immunofluorescence pattern was consistent with binding to the intercalated disc [26].
• Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus [4].
• When the cloned rat elastase I gene with 7 kb upstream and 5 kb downstream flanking sequences was introduced into mice by microinjection into fertilized eggs, the gene was expressed in a pancreas-specific manner [45].
• Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches [46].
• Similar transformations occur in organ cultures employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the developmental plasticity of the pancreas and that precise spatial and temporal control of tissue interactions are required for development of both organs [47].

References