Insulin attenuates agonist-mediated calcium mobilization in cultured rat vascular smooth muscle cells.

Saito, Fumio; Hori, Mark T.; Fittingoff, M; Hino, T; Tuck, Michael L.

doi:10.1172/jci116685

Cited by 69 publications

(47 citation statements)

References 55 publications

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“…VSMCs were isolated from rat thoracic aorta (male Sprague-Dawley rats, 250 to 300 g) by enzymatic dispersion 10,24 and grown in a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 (Sigma Chemical Co) supplemented with 10% fetal calf serum (FCS, Tissue Culture Biologicals), 50 U/mL penicillin, and 50 g/mL streptomycin (Sigma). Confluent cultures were passaged after treatment with trypsin-EDTA and reseeding at a 1:4 ratio in fresh media.…”

Section: Cell Culturementioning

confidence: 99%

“…Cells (4 to 12 passages) were seeded into 100-mm (P100) culture dishes and reached confluence in 5 to 7 days. 10 Cell lines were randomly screened for smooth muscle actin expression by immunofluorescent staining with anti-rat smooth muscle actin (Enzo Diagnostics Inc) and fluorescence-conjugated rabbit anti-mouse IgG (Cappel Laboratories, Organon Teknica Corp).…”

Section: Cell Culturementioning

confidence: 99%

“…7 The mechanisms of the action of insulin on vascular tone include alterations in nitric oxide 9 and cytosolic calcium. 10 The growth effects of insulin may be the most important factor in increased cardiovascular risk. 11,12 Different forms of insulin such as insulin-like growth factor-I (IGF-I) 12 and proinsulin 13 participate along with insulin to stimulate vascular growth and atherosclerosis.…”

mentioning

confidence: 99%

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Insulin-Mediated Growth in Aortic Smooth Muscle and the Vascular Renin-Angiotensin System

Kamide¹,

Hori²,

Zhu³

et al. 1998

Hypertension

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Abstract-Insulin has been shown to directly affect blood vessel tone and to promote vascular hypertrophy, but the mechanism of these actions remains uncertain. Because angiotensin I (Ang I)-converting enzyme inhibitors have been shown to improve insulin action and to impede the progression of vascular hypertrophy in hypertensive animal models, it is possible that the vascular properties of insulin may be mediated through the tissue renin-angiotensin system (RAS). To evaluate this relationship, we first investigated the effect of insulin on components of the RAS using cultured rat vascular smooth muscle cells (VSMCs). Insulin treatment (1000 U/mL) markedly increased angiotensinogen mRNA expression and angiotensinogen production. We next investigated the role of the RAS in insulin-mediated cell proliferation, using [ H]thymidine uptake. In summary, insulin induced significant stimulation of angiotensinogen expression and production and stimulated growth similar to that seen with Ang II in cultured rat VSMCs. Inhibition of Ang II production or its binding to the Ang II type 1 (AT 1 ) receptor inhibited insulin-mediated growth in a fashion similar to that seen with inhibition of Ang II-mediated growth. Thus, insulin can modulate the vascular RAS, and the effect of insulin on vascular growth may be via direct effects on angiotensinogen expression and translation operative through both the AT 1 receptor and the conversion of Ang I to Ang II. (Hypertension. 1998;32:482-487.)

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Section: Cell Culturementioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

mentioning

confidence: 99%

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Insulin-Mediated Growth in Aortic Smooth Muscle and the Vascular Renin-Angiotensin System

Kamide¹,

Hori²,

Zhu³

et al. 1998

Hypertension

View full text Add to dashboard Cite

show abstract

“…Insulin seems to have mixed effects on calcium flux, with some investigators demonstrating attenuation of inward calcium currents in rat VSMC in response to arginine vasopressin (11) and angiotensin II (12), and others showing stimulation of calcium uptake (13). In this study, we examined the effect of insulin on calcification of rat VSMC, and on VSMC phosphate and calcium transport.…”

Section: Introductionmentioning

confidence: 99%

Insulin attenuates vascular smooth muscle calcification but increases vascular smooth muscle cell phosphate transport

et al. 2007

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Medial artery vascular smooth muscle cell (VSMC) calcification increases the risk of cardiovascular mortality in type 2 diabetes. However, the influence of insulin on VSMC calcification is unclear. We explored the effects of insulin on rat VSMC calcification in vitro and found that in a dose-dependent fashion, insulin attenuates VSMC calcification induced by high phosphate conditions as quantified by the OCPC method. In an in vitro model of insulin resistance in which cells are exposed to elevated insulin concentrations and the PI 3-kinase pathway is selectively inhibited, increased VSMC calcification was observed, suggesting that the PI 3-kinase pathway is involved in this attenuating effect of insulin. We postulated that insulin may also have an effect on phosphate or calcium transport in VSMC. We found that insulin increases phosphate transport at 3 hr and 24 hr. This effect was mediated by increased V max for phosphate transport but not K m . Because type III sodium-phosphate co-transporters Pit-1 and Pit-2 are found in VSMC, we examined their expression by Western blot and real-time RT-PCR. Insulin stimulates Pit-1 mRNA modestly (*p<0.01 vs. control), an effect mediated by PD98059 but not by wortmannin. Pit-1 protein expression is induced by insulin, an effect also mediated by PD98059 (*p<0.001 vs. insulin alone). Results for Pit-2 were mixed. Our results suggest a role for insulin in attenuating VSMC calcification which may be disrupted in selective insulin signaling impairment seen in insulin resistance. This effect of insulin contrasts with its effect to induce phosphate transport in VSMC.

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“…Results of studies of the effects of insulin on {Ca2+]; metabolism have been inconsistent. In animals, insulin has been reported to increase [Ca2±Jj (19,20), decrease [Ca2±]1 (21) or have no effect on it (22,23). In a human study, insulin has been reported not to change platelet [Ca2+]; of normotensive subjects in vitro and in vivo (24).…”

Section: Discussionmentioning

confidence: 95%

Inhibitory Effects of Insulin on Intracellular Calcium and Aggregatory Response of Platelets Are Impaired in Hypertensive Subjects with Insulin Resistance.

et al. 1997

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To determine the effects of insulin on intracellular calcium and platelet aggregatory responses in hypertensive subjects with insulin resistance, we measured insulin sensitivity in terms of glucose disposal rate (GDR) by the hyperinsulinemic euglycemic clamp technique (GC) in 14 non-diabetic untreated hypertensive subjects, and determined basal ([Ca2+] The association between hypertension and insulin resistance is well recognized (1). Possible mechanisms by which insulin participates in the pathogenesis of hypertension include increased sodium reabsorption in the kidney (2, 3), activation of the sympathetic nervous system (4), and proliferation of vascular smooth muscle cells (5, 6). On the other hand, evidence against an association between hypertension and insulin resistance includes the following findings: hypertension is not observed in patients with insulinoma despite the presence of hyperinsulinemia (7), continuous infusion of highdose insulin for 7 days does not increase blood pressure in dogs (8), and acute increases in plasma insulin within the physiological range increase sympathetic neural outflow but produce forearm vasodilatation and do not elevate arterial pressure in humans (9) . Insulin has dual pressor and depressor (vasodilatory) effects (10). Also, insulin attenuates both agonist-stimulated vasoconstriction (I1) and aggregatory response of platelets (12, 13).If the vasodilatory and antiaggregatory effects of insulin were impaired in hypertensive subjects with insulin resistance, an association between hypertension and insulin resistance would be supported. We therefore measured insulin sensitivity in peripheral glucose utilization as determined by glucose clamp, intracellular calcium concentration in platelets as a marker of the vasodilatory effect of insulin on vascular smooth muscle cells, and platelet aggregation before and during glucose clamp, and examined the relationship between insulin resistance and the effects of insulin on intracellular calcium concentration and platelet aggregation in hypertensive subjects. MethodsThe subjects were 14 men with non-diabetic untreated essential hypertension. Insulin sensitivity in terms of glucose disposal rate (GDR) was determined by an artificial endocrine pancreas using the hyperinsulinemic euglycemic clamp technique (GC). Venous blood was drawn from subjects to measureFrom the * 1Department

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Insulin attenuates agonist-mediated calcium mobilization in cultured rat vascular smooth muscle cells.

Cited by 69 publications

References 55 publications

Insulin-Mediated Growth in Aortic Smooth Muscle and the Vascular Renin-Angiotensin System

Insulin-Mediated Growth in Aortic Smooth Muscle and the Vascular Renin-Angiotensin System

Insulin attenuates vascular smooth muscle calcification but increases vascular smooth muscle cell phosphate transport

Inhibitory Effects of Insulin on Intracellular Calcium and Aggregatory Response of Platelets Are Impaired in Hypertensive Subjects with Insulin Resistance.

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