Linked Life Data

18270301

Source:http://linkedlifedata.com/resource/pubmed/id/18270301

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-2
pubmed:abstractText
Insulin-like growth factor I (IGF-I) is normally produced from hepatocytes and various other cells and tissues, including the pancreas, and is known to stimulate islet cell replication in vitro, prevent Fas-mediated beta-cell destruction and delay the onset of diabetes in nonobese diabetic mice. Recently, however, the notion that IGF-I stimulates islet cell growth has been challenged by the results of IGF-I and receptor gene targeting. To test the effects of a general, more profound increase in circulating IGF-I on islet cell growth and glucose homeostasis, we have characterized MT-IGF mice, which overexpress the IGF-I gene under the metallothionein I promoter. In early reports, a 1.5-fold-elevated serum IGF-I level caused accelerated somatic growth and pancreatic enlargement. We demonstrated that the transgene expression, although widespread, was highly concentrated in the beta-cells of the pancreatic islets. Yet, islet cell percent and pancreatic morphology were unaffected. IGF-I overexpression resulted in significant hypoglycemia, hypoinsulinemia, and improved glucose tolerance but normal insulin secretion and sensitivity. Pyruvate tolerance test indicated significantly suppressed hepatic gluconeogenesis, which might explain the severe hypoglycemia after fasting. Finally, due to a partial prevention of beta-cell death against onset of diabetes and/or the insulin-like effects of IGF-I overexpression, MT-IGF mice (which overexpress the IGF-I gene under the metallothionein I promoter) were significantly resistant to streptozotocin-induced diabetes, with diminished hyperglycemia and prevention of weight loss and death. Although IGF-I might not promote islet cell growth, its overexpression is clearly antidiabetic by improving islet cell survival and/or providing insulin-like effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E928-38
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18270301-Animals, pubmed-meshheading:18270301-Blotting, Northern, pubmed-meshheading:18270301-Cell Proliferation, pubmed-meshheading:18270301-Diabetes Mellitus, Experimental, pubmed-meshheading:18270301-Fluorescent Antibody Technique, pubmed-meshheading:18270301-Gluconeogenesis, pubmed-meshheading:18270301-Glucose Tolerance Test, pubmed-meshheading:18270301-Humans, pubmed-meshheading:18270301-Hypoglycemia, pubmed-meshheading:18270301-Immunohistochemistry, pubmed-meshheading:18270301-Insulin, pubmed-meshheading:18270301-Insulin Resistance, pubmed-meshheading:18270301-Insulin-Like Growth Factor I, pubmed-meshheading:18270301-Islets of Langerhans, pubmed-meshheading:18270301-Metallothionein, pubmed-meshheading:18270301-Mice, pubmed-meshheading:18270301-Mice, Transgenic, pubmed-meshheading:18270301-Pyruvates, pubmed-meshheading:18270301-RNA, pubmed-meshheading:18270301-Rats, pubmed-meshheading:18270301-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2008
pubmed:articleTitle
A general and islet cell-enriched overexpression of IGF-I results in normal islet cell growth, hypoglycemia, and significant resistance to experimental diabetes.
pubmed:affiliation
Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't