Abstract

Laight, David W; Kaw, Amar V.; Carrier, Martin; Änggård, Erik

doi:10.1111/j.2042-7158.1998.tb03321.x

Cited by 14 publications

(6 citation statements)

References 29 publications

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“…Insulin's effect of increasing vasodilation has also been observed in isolated organ bath vascular strip preparations [41] where it increased endothelium-dependent vascular smooth muscle relaxation. Furthermore, insulin appears to blunt the responses to a number of vasoconstrictor agents [42,43,44].…”

Section: In Vitro Studiesmentioning

confidence: 74%

Vascular function, insulin resistance and fatty acids

Steinberg

Baron²

2002

Diabetologia

308

179

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Over the past 10 years it has become clear that intact vascular function, especially at the level of the endothelium, is paramount in the prevention or delay of cardiovascular disease. It has also become clear that insulin itself, in addition to its metabolic actions, directly effects vascular endothelium and smooth muscle. Insulin, at normal physiologic concentrations, causes changes in skeletal muscle blood flow in healthy, insulin-sensitive subjects. Insulin's effect on the endothelium is mediated through its own receptor and insulin signalling pathways, resulting in the increased release of nitric oxide. Insulin's vascular actions are impaired in insulin-resistant conditions such as obesity, Type II (non-insulin-dependent) diabetes mellitus and hypertension, which could contribute to the excessive rates of cardiovascular disease in these groups. Insulin-resistant states of obesity and Type II diabetes show a multitude of metabolic abnormalities that could cause vascular dysfunction. Non-esterified fatty acid levels increase long before hyperglycaemia becomes present. Raised non-esterified fatty acids impair insulin's effect on glucose uptake in skeletal muscle and the vascular endothelium and thus could have detrimental effects on the vasculature, leading to premature cardiovascular disease. [Diabetologia (2002) 45:623-634]

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Section: In Vitro Studiesmentioning

confidence: 74%

Vascular function, insulin resistance and fatty acids

Steinberg

Baron²

2002

Diabetologia

308

179

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“…Furthermore, platelet-mediated relaxation was not detected when platelets from eNOS -/-used were substituted in the protocol. Controversy exists as to whether the acute administration of physiologically relevant concentrations of insulin leads to a rapid activation of eNOS in isolated vascular preparations (Laight et al 1998) and the data from the study by Randriamboavonjy et al (2004) may provide the missing link to explain insulin-mediated vasodilatation.…”

Section: Role Of Platelet Enos In Insulin-mediated Vasodilatationmentioning

confidence: 98%

Twenty-five years since the discovery of endothelium-derived relaxing factor (EDRF): does a dysfunctional endothelium contribute to the development of type 2 diabetes?

Triggle

Howarth²,

Cheng³

et al. 2005

Can. J. Physiol. Pharmacol.

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Twenty-five years ago, the discovery of endothelium-derived relaxing factor opened a door that revealed a new and exciting role for the endothelium in the regulation of blood flow and led to the discovery that nitric oxide (NO) multi-tasked as a novel cell-signalling molecule. During the next 25 years, our understanding of both the importance of the endothelium as well as NO has greatly expanded. No longer simply a barrier between the blood and vascular smooth muscle, the endothelium is now recognized as a complex tissue with heterogeneous properties. The endothelium is the source of not only NO but also numerous vasoactive molecules and signalling pathways, some of which are still not fully characterized such as the putative endothelium-derived relaxing factor. Dysfunction of the endothelium is a key risk factor for the development of macro- and microvascular disease and, by coincidence, the discovery that NO was generated in the endothelium corresponds approximately in time with the increased incidence of type 2 diabetes. Primarily linked to dietary and lifestyle changes, we are now facing a global pandemic of type 2 diabetes. Characterized by insulin resistance and hyperglycaemia, type 2 diabetes is increasingly being diagnosed in adolescents as well as children. Is there a link between dietary-related hyperglycaemic insults to the endothelium, blood flow changes, and the development of insulin resistance? This review explores the evidence for and against this hypothesis.

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“…It has been demonstrated using a number of techniques that insulin leads to vasorelaxation in vivo and ex vivo (32)(33)(34). Furthermore, insulinmediated vasodilation is inhibited by pharmacological blockade of NO production in humans (32,35) or by deletion of the eNOS gene in mice (36), demonstrating that the vasorelaxant properties of insulin are largely NO dependent.…”

Section: Igf-i and Igf Binding Proteins In Cardiovascular Riskmentioning

confidence: 98%

Vascular Endothelial Function and Blood Pressure Homeostasis in Mice Overexpressing IGF Binding Protein-1

Wheatcroft¹,

Kearney²,

Shah³

et al. 2003

Diabetes

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IGFs and their binding proteins (IGFBPs) play a significant role in metabolic regulation, and there is growing evidence that they also exert important vascular effects. IGFBP-1 contributes to glucose counterregulation, and observational studies demonstrate an inverse association between circulating IGFBP-1 levels and cardiovascular risk factors. Furthermore, IGFBP-1 levels are lower in subjects with overt macrovascular disease. We therefore hypothesized that IGFBP-1 exerts potentially beneficial effects, either directly or indirectly, on blood pressure regulation and vascular function. We tested this hypothesis using a unique transgenic mouse, which overexpresses human IGFBP-1, and explored the effect of this protein on metabolic, blood pressure, and vascular homeostasis. IGFBP-1-overexpressing mice exhibited postprandial hyperinsulinemia with preservation of glucocompetence and insulin sensitivity. Blood pressure was unchanged in the fasting state but was significantly lower in transgenic mice after a carbohydrate load. Aortic rings from IGFBP-1-overexpressing mice were hypocontractile in response to vasoconstrictors, and relaxation responses were unimpaired. Basal nitric oxide production was increased and endothelial nitric oxide synthase mRNA expression upregulated in aortae of these mice. Our data suggest that IGFBP-1 plays an important and potentially beneficial role in regulating metabolic and vascular homeostasis. Diabetes 52: [2075][2076][2077][2078][2079][2080][2081][2082] 2003 I t is now established that a key early event in the development of atherosclerosis is vascular endothelial cell dysfunction (1). A characteristic feature of endothelial dysfunction is a reduction in the bioactivity of the antiatherosclerotic molecule nitric oxide (NO) (2). The evidence is compelling that abnormalities of metabolism may lead to a reduction in NO bioavailability and hence play an important role in the pathophysiology of cardiovascular atherosclerosis (3,4).Insulin is a key peptide in metabolic homeostasis, but IGF-I may also play an important complementary role in the maintenance of normoglycemia (5). Recently, it has been demonstrated that insulin and IGF-I can increase endothelial cell production of NO (6). Resistance to insulin's glucoregulatory actions is associated with conditions characterized by accelerated atherosclerosis, including type 2 diabetes, hypertension, and obesity (7). Consonant with this, robust evidence has established insulin resistance and hyperinsulinemia as independent risk factors for the development of coronary artery disease (8,9), although a potential contribution of IGF-I and its regulatory proteins was not assessed in these studies.Only a small fraction of IGF-I is present in the circulation in the active free form. A substantial proportion of circulating IGF-I is bound to a family of six binding proteins (IGFBPs), which have a number of physiological roles, including modulation of IGF-I bioavailability at target cells (10,11). One of these binding proteins, IGFBP-1, has been prop...

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Abstract

Cited by 14 publications

References 29 publications

Vascular function, insulin resistance and fatty acids

Vascular function, insulin resistance and fatty acids

Twenty-five years since the discovery of endothelium-derived relaxing factor (EDRF): does a dysfunctional endothelium contribute to the development of type 2 diabetes?

Vascular Endothelial Function and Blood Pressure Homeostasis in Mice Overexpressing IGF Binding Protein-1

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