Linked Life Data

12031967

Source:http://linkedlifedata.com/resource/pubmed/id/12031967

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-5-28
pubmed:abstractText
To test the hypothesis that c-Myc plays an important role in beta-cell growth and differentiation, we generated transgenic mice overexpressing c-Myc in beta-cells under control of the rat insulin II promoter. F(1) transgenic mice from two founders developed neonatal diabetes (associated with reduced plasma insulin levels) and died of hyperglycemia 3 days after birth. In pancreata of transgenic mice, marked hyperplasia of cells with an altered phenotype and amorphous islet organization was displayed: islet volume was increased threefold versus wild-type littermates. Apoptotic nuclei were increased fourfold in transgenic versus wild-type mice, suggesting an increased turnover of beta-cells. Very few cells immunostained for insulin; pancreatic insulin mRNA and content were markedly reduced. GLUT2 mRNA was decreased, but other beta-cell-associated genes (IAPP [islet amyloid pancreatic polypeptide], PDX-1 [pancreatic and duodenal homeobox-1], and BETA2/NeuroD) were expressed at near-normal levels. Immunostaining for both GLUT2 and Nkx6.1 was mainly cytoplasmic. The defect in beta-cell phenotype in transgenic embryos (embryonic days 17-18) and neonates (days 1-2) was similar and, therefore, was not secondary to overt hyperglycemia. When pancreata were transplanted under the kidney capsules of athymic mice to analyze the long-term effects of c-Myc activation, beta-cell depletion was found, suggesting that, ultimately, apoptosis predominates over proliferation. In conclusion, these studies demonstrate that activation of c-Myc in beta-cells leads to 1) increased proliferation and apoptosis, 2) initial hyperplasia with amorphous islet organization, and 3) selective downregulation of insulin gene expression and the development of overt diabetes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1793-804
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12031967-Animals, pubmed-meshheading:12031967-Apoptosis, pubmed-meshheading:12031967-Cell Division, pubmed-meshheading:12031967-Diabetes Mellitus, pubmed-meshheading:12031967-Female, pubmed-meshheading:12031967-Gene Expression, pubmed-meshheading:12031967-Gene Expression Regulation, pubmed-meshheading:12031967-Genes, myc, pubmed-meshheading:12031967-Glucose Transporter Type 2, pubmed-meshheading:12031967-Homeodomain Proteins, pubmed-meshheading:12031967-Humans, pubmed-meshheading:12031967-Insulin, pubmed-meshheading:12031967-Islets of Langerhans, pubmed-meshheading:12031967-Male, pubmed-meshheading:12031967-Mice, pubmed-meshheading:12031967-Mice, Inbred C57BL, pubmed-meshheading:12031967-Mice, Nude, pubmed-meshheading:12031967-Mice, Transgenic, pubmed-meshheading:12031967-Mitosis, pubmed-meshheading:12031967-Monosaccharide Transport Proteins, pubmed-meshheading:12031967-Pancreas Transplantation, pubmed-meshheading:12031967-Promoter Regions, Genetic, pubmed-meshheading:12031967-RNA, Messenger, pubmed-meshheading:12031967-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2002
pubmed:articleTitle
Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes.
pubmed:affiliation
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't