Linked Life Data

16731793

Source:http://linkedlifedata.com/resource/pubmed/id/16731793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-5-29
pubmed:abstractText
Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the cAMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from advanced fasting hyperinsulinemia and early development of hyper-glycemia, in spite of hyperinsulinemia, as well as impaired capacity of insulin to suppress plasma glucose in an insulin tolerance test. In vitro analyses of insulin-stimulated lipogenesis in adipocytes and glucose uptake in skeletal muscle did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet perturbations, such as centrally located alpha-cells and reduced immunostaining for insulin and GLUT2 in islets from RIP-PDE3B/2 mice. Additionally, in vitro experiments revealed that the insulin secretory response to glucagon-like peptide-1 stimulation was markedly reduced in islets from high-fat-fed RIP-PDE3B/2 mice. We conclude that accurate regulation of beta-cell cAMP is necessary for adequate islet adaptation to a perturbed metabolic environment and protective for the development of glucose intolerance and insulin resistance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
189
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
629-41
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16731793-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:16731793-Adaptation, Physiological, pubmed-meshheading:16731793-Animals, pubmed-meshheading:16731793-Blood Glucose, pubmed-meshheading:16731793-Cyclic AMP, pubmed-meshheading:16731793-Cyclic Nucleotide Phosphodiesterases, Type 3, pubmed-meshheading:16731793-Diabetes Mellitus, Type 2, pubmed-meshheading:16731793-Dietary Fats, pubmed-meshheading:16731793-Gene Expression, pubmed-meshheading:16731793-Glucagon-Like Peptide 1, pubmed-meshheading:16731793-Glucose Transporter Type 2, pubmed-meshheading:16731793-Immunohistochemistry, pubmed-meshheading:16731793-Insulin, pubmed-meshheading:16731793-Insulin Resistance, pubmed-meshheading:16731793-Insulin-Secreting Cells, pubmed-meshheading:16731793-Liver, pubmed-meshheading:16731793-Mice, pubmed-meshheading:16731793-Mice, Inbred C57BL, pubmed-meshheading:16731793-Mice, Inbred CBA, pubmed-meshheading:16731793-Mice, Transgenic, pubmed-meshheading:16731793-Triglycerides
pubmed:year
2006
pubmed:articleTitle
Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B.
pubmed:affiliation
Department of Experimental Medical Science, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden. helena.walz@med.lu.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't