Source:http://linkedlifedata.com/resource/pubmed/id/11978638
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
2002-4-29
|
pubmed:abstractText |
Type 2 (non-insulin-dependent) diabetes results from decreased insulin action in peripheral target tissues (insulin resistance) and impaired pancreatic beta-cell function. These defects reflect both genetic components and environmental risk factors. Recently, the common Gly(972)-->Arg amino acid polymorphism of insulin receptor substrate 1 (Arg(972) IRS-1) has been associated with human type 2 diabetes. In this study, we report on some functional and morphological properties of isolated human islets carrying the Arg(972) IRS-1 polymorphism. Insulin content was lower in variant than control islets (94 +/- 47 vs. 133 +/- 56 microU/islet; P < 0.05). Stepwise glucose increase (1.7 to 16.7 mmol/l) significantly potentiated insulin secretion from control islets, but not Arg(972) IRS-1 islets, with the latter also showing a relatively lower response to glyburide and a significantly higher response to arginine. Proinsulin release mirrored insulin secretion, and the insulin-to-proinsulin ratio in response to arginine was significantly lower from Arg(972) IRS-1 islets than from control islets. Glucose utilization and oxidation did not differ in variant and wild-type islets at both low and high glucose levels. Electron microscopy showed that Arg(972) IRS-1 beta-cells had a severalfold greater number of immature secretory granules and a lower number of mature granules than control beta-cells. In conclusion, Arg(972) IRS-1 islets have reduced insulin content, impaired insulin secretion, and a lower amount of mature secretory granules. These alterations may account for the increased predisposition to type 2 diabetes in individuals carrying the Gly(972)-->Arg amino acid polymorphism of IRS-1.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0012-1797
|
pubmed:author |
pubmed-author:AnelloMarcelloM,
pubmed-author:BergaminiEttoreE,
pubmed-author:BoggiUgoU,
pubmed-author:Del GuerraSilviaS,
pubmed-author:Del PratoStefanoS,
pubmed-author:FedericiMassimoM,
pubmed-author:LauroRenatoR,
pubmed-author:LupiRobertoR,
pubmed-author:MarchettiPieroP,
pubmed-author:MarselliLorellaL,
pubmed-author:MasiniMatildeM,
pubmed-author:MoscaFrancoF,
pubmed-author:PatanèGiovanniG,
pubmed-author:PiroSalvatoreS,
pubmed-author:PurrelloFrancescoF,
pubmed-author:SestiGiorgioG
|
pubmed:issnType |
Print
|
pubmed:volume |
51
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1419-24
|
pubmed:dateRevised |
2011-11-17
|
pubmed:meshHeading |
pubmed-meshheading:11978638-Adolescent,
pubmed-meshheading:11978638-Adult,
pubmed-meshheading:11978638-Diabetes Mellitus, Type 2,
pubmed-meshheading:11978638-Female,
pubmed-meshheading:11978638-Humans,
pubmed-meshheading:11978638-Insulin,
pubmed-meshheading:11978638-Insulin Receptor Substrate Proteins,
pubmed-meshheading:11978638-Islets of Langerhans,
pubmed-meshheading:11978638-Male,
pubmed-meshheading:11978638-Microscopy, Electron,
pubmed-meshheading:11978638-Middle Aged,
pubmed-meshheading:11978638-Phosphoproteins,
pubmed-meshheading:11978638-Polymorphism, Single Nucleotide,
pubmed-meshheading:11978638-Secretory Vesicles
|
pubmed:year |
2002
|
pubmed:articleTitle |
Insulin secretory function is impaired in isolated human islets carrying the Gly(972)-->Arg IRS-1 polymorphism.
|
pubmed:affiliation |
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa, Italy. marchant@immr.med.unipi.it
|
pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|