Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-3-14
pubmed:abstractText
Previous clinical studies showed an apparent correlation between hypertension and insulin resistance, and patients with diabetes are known to have increased blood pressure responsiveness to salt loading. To investigate the effect of high salt intake on insulin sensitivity and the insulin signaling pathway, a high-salt diet (8% NaCl) or a normal diet was given to 7-week-old SD rats for 2 weeks. High salt-fed rats developed slightly but significantly higher systolic blood pressure than controls (133 +/- 2 vs. 117 +/- 2 mmHg, P < 0.001), with no change in food intake or body weight. High salt-fed rats were slightly hyperglycemic (108.5 +/- 2.8 vs. 97.8 +/- 2.5 mg/dl, P = 0.01) and slightly hyperinsulinemic (0.86 +/- 0.07 vs. 0.61 +/- 0.06 ng/ml, P = 0.026) in the fasting condition, as compared with controls. Hyperinsulinemic-euglycemic clamp study revealed a 52.7% decrease in the glucose infusion rate and a 196% increase in hepatic glucose production in high salt-fed rats, which also showed a 66.4% decrease in 2-deoxyglucose uptake into isolated skeletal muscle and a 44.5% decrease in insulin-induced glycogen synthase activation in liver, as compared with controls. Interestingly, despite the presence of insulin resistance, high salt-fed rats showed enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, IRS-2 (liver and muscle), and IRS-3 (liver only). Phosphatidylinositol (PI) 3-kinase activities associated with IRS and phosphotyrosine in the insulin-stimulated condition increased 2.1- to 4.1-fold, as compared with controls. Insulin-induced phosphorylation of Ser-473 of Akt and Ser-21 of glycogen synthase kinase-3 also increased 2.9- and 2-fold, respectively, in the liver of the high salt-fed rats. Therefore, in both the liver and muscle of high salt-fed rats, intracellular insulin signaling leading to PI 3-kinase activation is enhanced and insulin action is attenuated. The hyperinsulinemic-euglycemic clamp study showed that decreased insulin sensitivity induced with a high-salt diet was not reversed by administration of pioglitazone. The following can be concluded: 1) a high-salt diet may be a factor promoting insulin resistance, 2) the insulin-signaling step impaired by high salt intake is likely to be downstream from PI 3-kinase or Akt activation, and 3) this unique insulin resistance mechanism may contribute to the development of diabetes in patients with hypertension.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2,4-thiazolidinedione, http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/Deoxyglucose, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Irs3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
573-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11246877-Animals, pubmed-meshheading:11246877-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:11246877-Deoxyglucose, pubmed-meshheading:11246877-Diet, Sodium-Restricted, pubmed-meshheading:11246877-Enzyme Activation, pubmed-meshheading:11246877-Glucose Clamp Technique, pubmed-meshheading:11246877-Glycogen Synthase, pubmed-meshheading:11246877-Glycogen Synthase Kinase 3, pubmed-meshheading:11246877-Glycogen Synthase Kinases, pubmed-meshheading:11246877-Insulin, pubmed-meshheading:11246877-Insulin Receptor Substrate Proteins, pubmed-meshheading:11246877-Insulin Resistance, pubmed-meshheading:11246877-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11246877-Liver, pubmed-meshheading:11246877-Male, pubmed-meshheading:11246877-Muscle, Skeletal, pubmed-meshheading:11246877-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11246877-Phosphoproteins, pubmed-meshheading:11246877-Phosphorylation, pubmed-meshheading:11246877-Protein-Serine-Threonine Kinases, pubmed-meshheading:11246877-Proto-Oncogene Proteins, pubmed-meshheading:11246877-Proto-Oncogene Proteins c-akt, pubmed-meshheading:11246877-Rats, pubmed-meshheading:11246877-Rats, Sprague-Dawley, pubmed-meshheading:11246877-Receptor, Insulin, pubmed-meshheading:11246877-Signal Transduction, pubmed-meshheading:11246877-Thiazoles, pubmed-meshheading:11246877-Thiazolidinediones, pubmed-meshheading:11246877-Tyrosine
pubmed:year
2001
pubmed:articleTitle
Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats.
pubmed:affiliation
Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
pubmed:publicationType
Journal Article, In Vitro