Linked Life Data

11287353

Source:http://linkedlifedata.com/resource/pubmed/id/11287353

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-4-5
pubmed:abstractText
Although chronic hyperinsulinemia has been shown to induce insulin resistance, the basic cellular mechanisms responsible for this phenomenon are unknown. The present study was performed 1) to determine the time-related effect of physiological hyperinsulinemia on glycogen synthase (GS) activity, hexokinase II (HKII) activity and mRNA content, and GLUT-4 protein in muscle from healthy subjects, and 2) to relate hyperinsulinemia-induced alterations in these parameters to changes in glucose metabolism in vivo. Twenty healthy subjects had a 240-min euglycemic insulin clamp study with muscle biopsies and then received a low-dose insulin infusion for 24 (n = 6) or 72 h (n = 14) (plasma insulin concentration = 121 +/- 9 or 143 +/- 25 pmol/l, respectively). During the baseline insulin clamp, GS fractional velocity (0.075 +/- 0.008 to 0.229 +/- 0.02, P < 0.01), HKII mRNA content (0.179 +/- 0.034 to 0.354 +/- 0.087, P < 0.05), and HKII activity (2.41 +/- 0.63 to 3.35 +/- 0.54 pmol x min(-1) x ng(-1), P < 0.05), as well as whole body glucose disposal and nonoxidative glucose disposal, increased. During the insulin clamp performed after 24 and 72 h of sustained physiological hyperinsulinemia, the ability of insulin to increase muscle GS fractional velocity, total body glucose disposal, and nonoxidative glucose disposal was impaired (all P < 0.01), whereas the effect of insulin on muscle HKII mRNA, HKII activity, GLUT-4 protein content, and whole body rates of glucose oxidation and glycolysis remained unchanged. Muscle glycogen concentration did not change [116 +/- 28 vs. 126 +/- 29 micromol/kg muscle, P = nonsignificant (NS)] and was not correlated with the change in nonoxidative glucose disposal (r = 0.074, P = NS). In summary, modest chronic hyperinsulinemia may contribute directly (independent of change in muscle glycogen concentration) to the development of insulin resistance by its impact on the GS pathway.
pubmed:grant
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
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E712-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11287353-Adult, pubmed-meshheading:11287353-Female, pubmed-meshheading:11287353-Glucose, pubmed-meshheading:11287353-Glucose Transporter Type 4, pubmed-meshheading:11287353-Glycogen, pubmed-meshheading:11287353-Glycogen Synthase, pubmed-meshheading:11287353-Hexokinase, pubmed-meshheading:11287353-Humans, pubmed-meshheading:11287353-Hyperinsulinism, pubmed-meshheading:11287353-Insulin, pubmed-meshheading:11287353-Isoenzymes, pubmed-meshheading:11287353-Male, pubmed-meshheading:11287353-Monosaccharide Transport Proteins, pubmed-meshheading:11287353-Muscle, Skeletal, pubmed-meshheading:11287353-Muscle Proteins, pubmed-meshheading:11287353-Oxidation-Reduction, pubmed-meshheading:11287353-RNA, Messenger, pubmed-meshheading:11287353-Reference Values, pubmed-meshheading:11287353-Time Factors
pubmed:year
2001
pubmed:articleTitle
Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis.
pubmed:affiliation
Division of Diabetes, Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas 78284, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.