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Titolo:
Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats
Autore:
Ogihara, T; Asano, T; Ando, K; Chiba, E; Sekine, N; Sakoda, H; Anai, M; Onishi, Y; Fujishiro, M; Ono, H; Shojima, N; Inukai, K; Fukushima, Y; Kikuchi, W; Fujita, T;
Indirizzi:
Univ Tokyo, Grad Sch Med, Dept Internal Med, Bunkyo Ku, Tokyo, Japan Univ Tokyo Tokyo Japan Med, Dept Internal Med, Bunkyo Ku, Tokyo, Japan Asahi Life Fdn, Inst Adult Dis, Tokyo, Japan Asahi Life Fdn Tokyo JapanAsahi Life Fdn, Inst Adult Dis, Tokyo, Japan
Titolo Testata:
DIABETES
fascicolo: 3, volume: 50, anno: 2001,
pagine: 573 - 583
SICI:
0012-1797(200103)50:3<573:IRWEIS>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLYCOGEN-SYNTHASE KINASE-3; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PLECKSTRIN HOMOLOGY DOMAIN; RECEPTOR SUBSTRATE-1; SKELETAL-MUSCLE; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; GLUCOSE-METABOLISM; DIABETES-MELLITUS; 3T3-L1 ADIPOCYTES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Asano, T Univ Tokyo, Grad Sch Med, Dept Internal Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo, Japan Univ Tokyo 7-3-1 Hongo Tokyo Japan u, 7-3-1 Hongo, Tokyo, Japan
Citazione:
T. Ogihara et al., "Insulin resistance with enhanced insulin signaling in high-salt diet-fed rats", DIABETES, 50(3), 2001, pp. 573-583

Abstract

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 glycogensynthase 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 a-fold, respectively, in the liver of the high salt-fed rats. Therefore, in both the liver and muscle off 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 highsalt 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.

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Documento generato il 13/07/20 alle ore 06:59:55