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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past decade, it became obvious that in contrast to defective insulin secretion in type I diabetes, defective insulin action (insulin resistance) is the most pertinent feature of type II diabetes. In addition, it has been known for a long time that obesity and insulin resistance are closely linked. Recently, hypertension also has been shown to often coincide with insulin resistance, although any causal relationships are still hypothetical. Last, several widely used pharmacological drugs such as diuretics, adrenergic blockers, and angiotensin-converting enzyme inhibitors may influence insulin sensitivity. Therefore, growing interest has emerged to most accurately measure insulin sensitivity. Although considerable knowledge has accumulated as to the actual mechanisms of insulin-dependent glucose transport, the signal transduction pathway of insulin remains poorly understood. When insulin sensitivity is measured, it is the overall glucose uptake that is quantified under controlled conditions. Other actions of insulin, such as the transport of ions, (e.g., sodium and potassium), synthesis of insulin-like growth factor-binding proteins, translocation of transporter proteins, and regulation of enzyme activities, are much more difficult to quantify. Of the many approaches used to quantify insulin action, the euglycemic hyperinsulinemic clamp technique has emerged as the most reliable tool, fulfilling clinical and scientific demands equally. In combination with tracer methodology and calorimetry, a detailed view into the quantitative aspects of insulin action at different target cells is possible. Whether insulin resistance extends to other known actions of insulin in addition to those on glucose metabolism remains open to debate.
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PMID:Determination of insulin sensitivity: methodological considerations. 128 39

Accelerated atherosclerosis accompanying diabetes mellitus, obesity, and some types of hypertension has been associated with hyperinsulinemia, augmented plasma plasminogen activator inhibitor type 1 (PAI-1), or both. We hypothesized that insulin and insulin-like growth factor type I (IGF-I) can influence synthesis of PAI-1, thereby potentially attenuating fibrinolysis. In HepG2 cells used as a model system, concentrations of insulin and IGF-I consistent with those seen in plasma independently stimulated PAI-1 synthesis. Accumulation of PAI-1 protein in conditioned medium over 24 hr was stimulated more with insulin alone than with the combination. Synergistic increases were evident, however, in the accumulation of PAI-1 protein over 48 hr with a concomitant increase in PAI-1 mRNA. A 10- to 20-fold increase in IGF binding protein I mRNA was seen 16-48 hr after exposure of the HepG2 cells to insulin and IGF-I, an increase abolished by cycloheximide. The results obtained are consistent with the hypothesis that hyperinsulinemia coupled with physiologic concentrations of IGF-I may attenuate fibrinolytic activity in vivo, thereby contributing to accelerated atherosclerosis.
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PMID:Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type I: implications for vascular disease in hyperinsulinemic states. 171 59

Hypertension causes biochemical and morphological changes in the vessel wall by unknown mechanisms. Locally produced substances may have a role in mediating these vascular changes. We have studied the expression of platelet-derived growth factor (PDGF) B chain and PDGF A chain, insulin-like growth factor (IGF)-I and IGF-II, endothelial cell growth factor (ECGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) in aortic tissue from normotensive rats and rats made hypertensive by deoxycorticosterone (DOC)/salt treatment. Using Northern blotting, we found that genes for each of these growth factors were transcriptionally active in the aorta of both normotensive and hypertensive rats. TGF-beta aortic mRNA levels increased up to threefold as a result of DOC/salt hypertension. In contrast, no major changes in the expression of either PDGF chain, IGF-I or II, ECGF, or bFGF were detectable. The results indicate that at least seven genes coding for growth factors that were shown previously to influence growth and function of vascular cells in vitro, are expressed in rat aorta in vivo. These findings support the hypothesis that synthesis and release of growth factors in the arterial wall are involved in autocrine and/or paracrine regulatory mechanisms. In addition, the increased expression of TGF-beta in vivo may have a role in mediating the aortic changes induced by hypertension.
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PMID:Growth factor expression in aorta of normotensive and hypertensive rats. 270 37

Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine systems that are involved with the local regulation of its own function. The endothelium plays a pivotal role in modulating the balance between thrombogenesis and thrombolysis. In addition, it secretes vasorelaxant and vasoconstrictive substances, growth factors and inflammatory mediators that exert paracrine influences on vascular myocyte function. The vascular myocyte also expresses autocrine substances which influence its own function. The autocrine systems include angiotensin, prostaglandins, platelet-derived growth factor, insulin-like growth factor and heparin. These local factors exert modulatory influences on myocyte contractility and growth. It is conceivable that genetic or acquired abnormalities of one or several of these check and balance systems can result in increased vascular tone, generalized vascular hypertrophy or hyperplasia, or a combination, and contribute to the pathogenesis of hypertension. These autocrine-paracrine systems may be important targets for antihypertensive drug development.
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PMID:Autocrine-paracrine mechanisms of vascular myocytes in systemic hypertension. 289 Dec 92

Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine systems that are involved with the local regulation of its own function (i.e., structure and growth). The endothelium secretes vasorelaxant and vasoconstrictive substances, growth factors and inflammatory mediators that exert paracrine influences on vascular myocyte function. The vascular myocyte also expresses autocrine substances that influence its own function. The autocrine systems include angiotensin, prostaglandins, platelet-derived growth factor, insulin-like growth factor and heparin. These local factors exert modulatory influences on myocyte contractility and growth. These autocrine and paracrine systems serve as an adaptive mechanism by which the vasculature autoregulates its structural and functional state. We speculate that an alteration in this delicate balance of these local factors, due to genetic or acquired abnormalities, can result in increased vascular tone and vessel hypertrophy and thereby contribute to the pathogenesis of hypertension.
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PMID:Cell biology of vascular hypertrophy in systemic hypertension. 305 93

Vascular smooth muscle cells (SMCs) occur throughout the vascular tree and have important physiological functions. They are also involved in pathological processes such as development and progression of atherosclerotic lesions, restenosis following angioplasty, and in hypertension. This review is focused on the role of the insulin-like growth factor (IGF) system in proliferation, migration, and hypertrophy of vascular SMCs and its interaction with insulin and other growth factors. The IGF-I receptor is highly expressed in SMCs in intact arteries and in cultured SMCs and is activated by binding of IGF-I to the two alpha-subunits. Insulin and IGF-II from the circulation can interact with the IGF-I receptor at higher concentrations. Insulin receptors are few or absent in SMCs and circulating insulin concentrations in vivo are probably too low for a direct action of insulin on the IGF-I receptor in SMCs. Receptor activation initiates a number of signal transduction pathways. Increased phosphatidylinositol turnover and calcium mobilization correlates with actin filament reorganization and stimulation of directed migration of the SMC in a gradient of IGF-I. The effects of IGF-I receptor activation on signal transduction pathways (eg, the MAP kinase cascade) implicated in DNA synthesis and proliferation are weak and this correlates with the meager mitogenic activity of IGF-I in SMC. Several components of the IGF-system in SMC are regulated by growth factors such as platelet-derived growth factor (PDGF)-BB and basic fibroblast growth factor (bFGF).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The insulin-like growth factor system in vascular smooth muscle: interaction with insulin and growth factors. 747 13

Insulin is a major regulator of circulating insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), suppressing the hepatic production of IGFBP-1. Postmenopausal age, obesity, hypertension, and impaired glucose tolerance, which are known risk factors for endometrial cancer, are all associated with hyperinsulinemia and insulin resistance. In this study, we investigated the relationship among serum insulin, glucose, insulin-like growth factors (IGF-I and IGF-II), and IGFBP-, -2, and -3 in 32 nondiabetic postmenopausal women with endometrial cancer and in 18 healthy controls. The mean fasting levels of glucose and insulin were higher, whereas the mean basal IGF-I, IGF-II, and IGFBP-3 levels were lower in the endometrial cancer patients than in the healthy control subjects. The mean fasting IGFBP-1 and IGFBP-2 levels did not differ between the groups, and no correlation was found between fasting insulin and IGFBP-1 concentrations or between insulin and IGFBP-2 concentrations in either of the study groups. During an oral glucose tolerance test, the mean glucose levels at 1 and 3 h as well as the mean insulin level at 3 h were significantly higher in the endometrial cancer patients than in the controls, and the area under the glucose curve was larger in the first group. An oral glucose load resulted in a similar fall in serum IGFBP-1 levels in endometrial cancer patients and controls (51% and 55% at 3 h). When the cancer patients were divided into two subgroups according to the body mass index (kilograms per m2), the obese group had higher glucose and insulin indices than the nonobese group. No difference was found by the same measures in healthy controls. The fasting serum IGFBP-1 levels tended to be lower in the obese than in the normal weight subjects, but the difference did not reach statistical significance. In summary, these results provide preliminary evidence that the inverse relation between fasting insulin and IGFBP-1, well established in children and young adults, disappears in elderly women, although short term suppression by insulin still occurs. Further, our data indicate that in addition to carbohydrate metabolism, postmenopausal women with endometrial cancer have alterations in their circulating IGF system compared to controls.
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PMID:Relationship between carbohydrate metabolism and serum insulin-like growth factor system in postmenopausal women: comparison of endometrial cancer patients with healthy controls. 768 14

Patients with acromegaly have significant morbidity and mortality, associated with cardiovascular disease. Acromegaly is often complicated by other diseases such as diabetes mellitus, hypertension, and coronary artery disease, so the existence of acromegalic cardiomyopathy remains uncertain. Cardiac performance was investigated in patients with uncomplicated acromegaly. A subgroup of hypertensive acromegalics was also studied. In addition, the effects of chronic octreotide therapy or surgery on cardiac structure and function in acromegaly were studied. Twenty-six patients and 15 healthy controls underwent gated blood-pool cardiac scintigraphy and echocardiography at rest and during exercise. Echocardiography was repeated after 6 months of octreotide therapy (n = 11). Cardiac scintigraphy was repeated after 12 and 24 months of octreotide therapy (n = 10) or 12 to 24 months after surgery (n = 8). ECG, blood pressure, and heart rate were monitored during cardiac scintigraphy. Left ventricular mass (LVM) was calculated from the findings of the echocardiography. Serum growth hormone (GH) levels and plasma insulin-like growth factor-1 (IGF-1) levels were monitored. LVM index was significantly higher (P < .003) in acromegalics than controls and in hypertensive acromegalics than normotensives, but all other indices of cardiac function were similar. Chronic octreotide decreased GH and IGF-1 levels and improved the structural abnormalities as measured by echocardiography. Chronic octreotide or surgery did not alter cardiac function parameters. Thus, important changes in cardiac structure and function occur in uncomplicated acromegaly, and improvements can be demonstrated after chronic octreotide therapy. Heart disease in acromegaly appears to be secondary to high circulating GH levels.
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PMID:Cardiovascular aspects in acromegaly: effects of treatment. 876 83

Gestational hypertension is associated with insulin-resistance; insulin and insulin-like growth factor-1 (IGF-1), acting through their receptors, play a role in the growth of the feto-placental unit. Since both receptors are exposed to the maternal circulation, it has been suggested that maternal metabolic abnormalities might affect placental insulin (HIR) and IGF-1 (IGF-1R) receptors. To clarify this issue, we characterized HIR and IGF-1R in placenta at term from normal women, normoinsulinaemic women with gestational hypertension (NGH), and hyperinsulinaemic women with gestational hypertension (HGH). Insulin binding was decreased in HGH women (B/T 0.12 +/- 0.03) compared to control and NGH women (B/T 0.18 +/- 0.07, p < 0.036; and 0.22 +/- 0.5, p < 0.009 respectively). Receptor affinity was lower in HGH women (ED50 0.95 +/- 0.32 nmol/l) than control and NGH women (ED50 0.42 +/- 0.19 nmol/l, p < 0.01; and 0.40 +/- 0.1 nmol/l, p < 0.007, respectively), whereas low-affinity Ex11+ isoform was higher in HGH women (Ex11+ 50 +/- 7, %) than in control and NGH women (Ex11+ 34 +/- 9%, p < 0.001; and 39 +/- 4%, p < 0.01, respectively). Increased expression of Ex11+ isoform was correlated with ED50 (r = 0.71; p < 0.002) and insulinaemia (r = 0.70, p < 0.002). IGF-I binding was increased in HGH women (B/T 0.17 +/- 0.03) compared to control and NGH women (B/T 0.09 +/- 0.05, p < 0.002; and 0.11 +/- 0.03, p < 0.002, respectively). IGF-IR affinity was similar in the three groups. The percentage of insulin/IGF-I hybrid receptors was increased in HGH women (85 +/- 3%) compared to control and NGH women (68 +/- 7%, p < 0.001; and 63 +/- 9%, p < 0.001, respectively), and was positively correlated with insulinaemia (r = 0.62, p < 0.018), ED50 of insulin binding (r = 0.62, p < 0.05), and maximal IGF-I binding (r = 0.69, p < 0.004); whereas it was inversely correlated with maximal insulin binding (r = -0.69, p < 0.004). Results provide the first evidence for altered expression of insulin/IGF-I hybrids found in insulin-resistance states.
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PMID:Increased expression of low-affinity insulin receptor isoform and insulin/insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension. 885 18

Endocrine disorders associated with diabetes mellitus are described. When blood glucose control deteriorates, observed endocrine abnormalities are as follows. 1) Blood GH levels increase. This elevation is small but enough to disturb insulin secretion and glucose metabolism. Plama insulin-like growth factor-1 levels decrease in spite of their strong relation with diabetic retinopathy. 2) Blood thyroid hormones show the similarity with low T3 syndrome. 3) Hyporeninemic hypoaldosteronism occurs especially with patients who have hypertension or moderate diabetic complications. 4) Plasma pancreatic glucagon levels are elevated. Amino acids induce hypersecretion but hypoglycemia fails to response normally. Glucose administration shows impaired inhibition or paradoxical hypersecretion. 5) Other plasma levels of pancreatic hormones such as gastrin, secretin, motilin and somatostatin are usually elevated.
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PMID:[Endocrine disorders associated with impaired glucose tolerance]. 891 25


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