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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin has cardiovascular actions and patients with essential hypertension display insulin resistance. A cross-sectional study of the R1 RFLP of the insulin receptor gene (INSR) was carried out in 67 hypertensive (HT) and 75 normotensive (NT) subjects whose parents had a similar blood pressure status at age greater than or equal to 50. The frequency of the minor (+) allele was 0.31 in HTs and 0.44 in NTs, and the difference between observed alleles in all subjects in each group was significant (chi 2 = 4.8, P less than 0.05). Allele frequencies of a BglI RFLP of the insulin gene, however, did not differ between the HT and NT groups. The data thus provide evidence in favour of an association of HT with a polymorphism at the INSR locus (19p13.3-13.2), so implicating this locus, and possibly a genetic variant of the insulin receptor itself, in HT.
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PMID:Association of a RFLP for the insulin receptor gene, but not insulin, with essential hypertension. 168 35

The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and 125I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glycohaemoglobin A1 measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 microU/ml; p less than 0.05). Glucagon - stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 microU/ml, p less than 0.05) and after 8 weeks (1.67 vs. 2.90 microU/ml, p less than 0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of 125I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.
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PMID:Effects of a new diuretic piretanide on glucose tolerance, insulin secretion and 125I-insulin binding. 388 96

The role of cellular insulin receptors in the mechanism of thiazide induced glucose intolerance was studied in 10 non-diabetics and six diet controlled type II diabetics with mild essential hypertension. Glucose tolerance tests (75 g) were performed at the start of the study, after one month of placebo and after one month on bendrofluazide 5 mg daily. Erythrocyte insulin receptor status was measured on each occasion in the fasting state. In non-diabetics, low affinity insulin receptor concentration increased after bendrofluazide but high affinity receptor concentration remained unchanged. In the diabetics, there was no change in either high or low affinity insulin receptor concentration. No change in insulin receptor affinity occurred in either group. In the long term, non-diabetics may maintain normal glucose tolerance on thiazide diuretics by increasing insulin receptor numbers. This adjustment did not occur in diabetic patients which may explain the deterioration in glucose tolerance.
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PMID:Possible role for insulin receptors in the mechanism of thiazide induced glucose tolerance. 659 19

We have analyzed single-stranded conformational polymorphism (SSCP) to screen for mutation in exon 17 of insulin receptor gene in 46 patients with hypertension and 49 normotensive controls. Three different SSCP patterns were detected in both patients and controls and the frequency of pattern I was 54.3% and 32.7% (chi 2 = 3.71, P = 0.05) in patients and controls respectively; The frequency of pattern II was 61.3% and 26.1% (chi 2 = 10.49, P = 0.001) in controls and patients respectively; the frequency of pattern III did not differ between controls and patients. Based on direct sequencing, the differences between pattern II and pattern I were explained by a mutation substituting at position 1040, GAG1040-->GAA1040, which suggests that codon GAA1040 may be a genetic marker for susceptibility to essential hypertension in Chinese.
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PMID:[Detection of mutation in insulin receptor gene in patients with essential hypertension]. 765

1. Recent molecular genetic studies have implicated the low-density-lipoprotein receptor gene locus (LDLR, at chromosome 19p13.2) in obesity in essential hypertensive patients and in the atherogenic lipoprotein phenotype. The present study examined genotypes for the obesity-associated ApaLI restriction fragment length polymorphism of LDLR, and genotypes for a hypertension-associated RsaI restriction fragment length polymorphism at the insulin receptor gene (INSR) locus, which is linked to LDLR, in relation to plasma lipids, body mass index and blood pressure in 27 obese and 57 non-obese Caucasians with severe essential hypertension, selected on the basis of having parents who were both hypertensive, and in 25 obese and 45 non-obese normotensive subjects selected on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma triacylglycerol and low-density-lipoprotein-cholesterol were elevated in hypertensive patients, but did not differ between the obese and non-obese hypertensive groups. Significant positive correlations were seen between body mass index and triacylglycerol and low-density-lipoprotein-cholesterol in the obese and non-obese hypertensive patients, respectively. In addition, obese hypertensive patients had significantly higher diastolic blood pressure than non-obese hypertensive patients. 3. The eight obese hypertensive patients who were homozygous for the obesity-associated 6.6 kb allele of the ApaLI restriction fragment length polymorphism of LDLR ('6.6. kb homozygotes') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m2] than the 18 heterozygotes (29 +/- 2.7 kg/m2) and the single subject who was homozygous for the 9.4 kb allele (29 kg/m2) (P = 0.012 by one-way analysis of variance). The body mass index of the eight hypertensive 6.6 kb homozygotes was also greater than the body mass index of 29 +/- 2.4 kg/m2 observed for the eight obese normotensive 6.6 kb homozygotes. In addition, the eight obese hypertensive 6.6 kb homozygotes had a higher plasma triacylglycerol [4.2 +/- 0.77 (SEM) mmol/l] than the 18 obese hypertensive heterozygotes (2.4 +/- 0.33 mmol/l; P = 0.045). Non-obese hypertensive patients showed no significant genotypic differences in relation to the LDLR restriction fragment length polymorphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the LDLR ApaLI restriction fragment length polymorphism in obese subjects (0.54) was not significantly greater than in non-obese subjects (0.48) [cf. the significantly (P = 0.004( different values of 0.63 and 0.39, respectively, in obese and non-obese hypertensive patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Significant relationships of plasma lipids and body mass index with polymorphisms at the linked low-density-lipoprotein receptor gene and insulin receptor gene loci (19p13.2) in essential hypertensive patients. 803 1

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension. 2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was tested by chi 2 analysis with one degree of freedom. 3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P < 0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P < 0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kallikrein, alpha 2- and beta 1-adrenoreceptor, atrial natriuretic factor and insulin genes. 4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension. 810 54

Insulin has been postulated to play a role in the pathophysiology of essential hypertension via an antinatriuretic action. To further explain the sodium insulin interaction in the kidney, we studied effects of different salt intakes on insulin receptor binding and mRNA levels in tissues from rats maintained on 0.07%, 0.3%, or 7.5% NaCl for 14 days. Scatchard analysis of competition data from in situ autoradiography studies resulted in curvilinear profiles, indicating the presence of either two classes of receptors or a single class of receptors with a negative cooperative hormone-receptor interaction. When data were analyzed using the two-site model, binding capacity of the high-affinity receptor site was significantly less in high-salt-fed rats. No significant differences between dietary groups were observed in apparent dissociation constants of the two receptor sites or in maximal binding capacity of the low-affinity, high-capacity site. Analysis of insulin binding to glomeruli, cortex, outer medulla, and inner medulla indicated that the high-salt diet was associated with decreased receptor density in all regions studied. Insulin receptor mRNA, as quantified by Northern and slot blot analysis, was inversely related to salt intake in absence of a change in plasma glucose, insulin, and corticosterone levels. Both 7.2- and 9.4-kb transcripts were similarly affected by dietary sodium content. Plasma renin concentration and renal renin mRNA levels were decreased but blood pressure was not affected by high-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dietary sodium chloride on insulin receptor number and mRNA levels in rat kidney. 830 82

Insulin resistance is an essential feature of a great variety of clinical disorders, like diabetes mellitus, obesity, essential hypertension, and is primarily due to a defect in hormone action at the cellular level. In the past decade application of novel research techniques including recombinant DNA technology have paved the way to understand the mechanisms of insulin action and its alterations at the molecular level. The first step in insulin action is the activation of the insulin receptor. The insulin receptor is a tetrameric protein consisting of two extracellular alpha- and two transmembrane beta-subunits. Binding of insulin to the alpha-subunit causes autophosphorylation of the intracellular beta-subunit region on tyrosine residues thereby activating the receptor. How the hormonal signal is subsequently transduced within the cell is still quiet unclear. The activated insulin receptor appears to couple to cytosolic receptor substrates which can affect different signaling cascades eliciting the pleiotropic hormone response on cell metabolism and growth. Most proteins involved in the signal transduction pathway of insulin are not known yet, but each of them might play a role in the various forms of insulin resistance. Taking the insulin receptor as an exemplary protein involved in insulin action we review molecular mechanisms regulating insulin receptor activity, gene expression, and the role of natural occurring insulin receptor gene mutations in patients with insulin resistant diabetes mellitus. It is outlined how the combination of both clinical medicine and molecular biology not only helps to understand insulin action and the pathogenesis of insulin resistance, but also leads to new avenues in the differential diagnosis, therapy, and possibly prevention of this heterogenous but most frequent metabolic and endocrine disorder.
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PMID:Molecular biology of insulin resistance. 847 20

This study evaluated whether hypertensive siblings had excess sharing of RsaI and SstI alleles of the insulin receptor gene compared with a random population. Thirty families consisting of 60 affected individuals with established hypertension were genotyped for the RsaI and SstI restriction fragment length polymorphisms and the resulting genotype data was analysed using the affected pedigree member method of linkage analysis. The hypertensive siblings were found to have increased sharing of INSR alleles; however, this linkage could not be confirmed using a maximum LOD score method. Thus, the results from this study do not support a role for the INSR gene in the genesis of essential hypertension in the population studied.
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PMID:Absence of genetic linkage between polymorphisms of the insulin receptor gene and essential hypertension. 852 86

The association of the polymorphisms of two candidate genes with essential hypertension was studied in 74 hypertensive and 118 normotensive subjects. Two restrictions endonucleases were used: PstI for the insulin receptor gene and PvuII for the apolipoprotein B gene. PstI RFLP in the INSR gene locus consists of two polymorphic alleles P1 (1800bp) and P2 (1500bp). Frequencies of these alleles in general population are 0.15 and 0.85 respectively. The results showed statistically significant association between P1 allele and homozygotus genotype P1P1 for the INSR gene and essential hypertension. Clinical data of homozygotus P1P1 individuals revealed earlier clinical onset and more severe course of the disease. PvuII RFLP in the apoB gene locus consists of two polymorphic alleles Pul (7900bp) and Pu2(5500 bp). Frequencies of these alleles in general population are 0.93 and 0.07 respectively. In the apoB gene analysis Pu1 and Pu2 allele frequencies were similar in both studied groups. However the higher frequency of homozygotus genotype Pu1Pu2 was observed in hypertension.
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PMID:[Polymorphic variability of apolipoprotein B genes and insulin receptor in essential hypertension]. 875 50


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