Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-12
pubmed:abstractText
Membrane microdomains rich in gangliosides are recognized as being critical for proper compartmentalization of insulin signaling. Plasma membrane-associated sialidase, NEU3, is a key enzyme for ganglioside hydrolysis. We previously reported that mice overexpressing NEU3 mainly in muscles developed severe insulin-resistant diabetes. To examine the possible contributions of NEU3 to in vivo insulin sensitivity and glucose tolerance, NEU3 was expressed by using adenoviral vectors in the livers of C57BL/6 mice on standard and high-fat diets, and insulin-resistant KKAy mice on standard diets. Hepatic NEU3 overexpression paradoxically improved glucose tolerance and insulin sensitivity in the C57BL/6 mice fed standard diets, and glucose tolerance in the C57BL/6 mice fed high-fat diets and in KKAy mice. Hepatic NEU3 overexpression increased hepatic glycogen deposition and triglyceride accumulation, and enhanced the hepatic peroxisome proliferator-activated receptor gamma and fetuin expression in the C57BL/6 mice on standard and high-fat diets, and in KKAy mice. Thin-layer chromatographic analysis demonstrated increased levels of GM1 and markedly reduced GM3 in the livers of mice with hepatic NEU3 overexpression (NEU3 mice). Basal and insulin-stimulated tyrosine phosphorylations of insulin receptor substrate 1 were significantly increased, but tyrosine phosphorylations of the insulin receptor and insulin receptor substrate 2 in the NEU3 liver were unchanged. Insulin-stimulated tyrosine phosphorylations of the insulin receptor were increased in adipose tissues of NEU3 mice. These results suggest that hepatic NEU3 overexpression improves insulin sensitivity and glucose tolerance through modification of ganglioside composition and peroxisome proliferator-activated receptor gamma signaling. Our findings also provide further evidence that NEU3 is an important regulator of insulin sensitivity and glucose tolerance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose, http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Liver Glycogen, http://linkedlifedata.com/resource/pubmed/chemical/Neu3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Neuraminidase, http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-0495
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
420-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17292733-Adenoviridae, pubmed-meshheading:17292733-Adipose Tissue, pubmed-meshheading:17292733-Animals, pubmed-meshheading:17292733-Blood Glucose, pubmed-meshheading:17292733-Glucose Tolerance Test, pubmed-meshheading:17292733-Humans, pubmed-meshheading:17292733-Insulin, pubmed-meshheading:17292733-Insulin Receptor Substrate Proteins, pubmed-meshheading:17292733-Liver, pubmed-meshheading:17292733-Liver Glycogen, pubmed-meshheading:17292733-Male, pubmed-meshheading:17292733-Mice, pubmed-meshheading:17292733-Mice, Inbred C57BL, pubmed-meshheading:17292733-Neuraminidase, pubmed-meshheading:17292733-PPAR gamma, pubmed-meshheading:17292733-Phosphoproteins, pubmed-meshheading:17292733-Phosphorylation, pubmed-meshheading:17292733-Receptor, Insulin, pubmed-meshheading:17292733-Triglycerides
pubmed:year
2007
pubmed:articleTitle
Increased hepatic expression of ganglioside-specific sialidase, NEU3, improves insulin sensitivity and glucose tolerance in mice.
pubmed:affiliation
Department of Metabolism and Diabetes, Tohoku University School of Medicine, Sendai 980-8574, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't