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

The spontaneous hypertensive rat is an animal model characterized by a syndrome of hypertension, insulin resistance and hyperinsulinaemia. To elucidate whether in analogy to other insulin resistant animal models an inactivity of the insulin receptor kinase or an alteration of the glucose transporter (GLUT 4) level in the skeletal muscle might contribute to the pathogenesis of insulin resistance we determined insulin receptor kinase activity and GLUT 4 level in the hindlimbs of spontaneous hypertensive rats and normotensive control rats. Normotensive normoinsulinaemic Lewis and Wistar rats were used as insulin sensitive controls, obese Zucker rats were used as an insulin resistant control with known reduced skeletal muscle insulin receptor kinase activity. Binding of 125I-insulin, crosslinking of 125I-B26-insulin, autophosphorylation in vitro with 32P-ATP and phosphorylation of the synthetic substrate Poly (Glu 4: Tyr 1) were performed after partial purification of solubilized receptors on wheat germ agglutinin columns. GLUT 4 levels were determined by Western blotting of subcellular muscle membranes. Insulin receptors from spontaneous hypertensive rats compared to those from Lewis and Wistar rats showed no difference of the binding characteristics or the in vitro auto- and substrate phosphorylation activity of the receptor, while in the Zucker rats the earlier described insulin receptor kinase defect was clearly evident. Western blots of subcellular muscle membrane fractions with antibodies against GLUT 4 revealed no difference in transporter levels. These data suggest that insulin resistance in spontaneous hypertensive rats is caused neither by an insulin receptor inactivity nor by a decreased number of glucose transporters in the skeletal muscle.
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PMID:Normal insulin receptor tyrosine kinase activity and glucose transporter (GLUT 4) levels in the skeletal muscle of hyperinsulinaemic hypertensive rats. 132 60

Obesity is a multifactorial disease with a marked genetic component. The situation is further complicated by the heterogeneity of obesity demonstrated by the topographical distribution of body fat, e.g. upper body (central) and lower body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger heritable tendency compared with total body fat. Central obesity is characterized by hyperinsulinaemia and insulin resistance, a feature in common with non-insulin dependent diabetes mellitus, hypertension and atherosclerosis. In order to study the molecular genetics of central obesity we have examined 56 severely obese (mean body mass index 40), unrelated British Caucasoid young non-diabetic women for associations of restriction fragment length polymorphism of candidate genes with anthropometric measurements and indices of insulin secretion and resistance. The candidate genes examined were insulin receptor, insulin sensitive glucose transporter and insulin. An association of the class 3 allele of the hypervariable region in the 5' flanking region of the insulin gene was found with upper segment obesity (P = 0.005). Furthermore, the class 3 allele was also associated with fasting hyperinsulinaemia (P = 0.01), stimulated insulin secretion (P = 0.01) and insulin resistance as calculated from the homeostatic model of assessment (HOMA; P = 0.008). No such associations were found with the other candidate genes studied. This data suggests that polymorphisms in the 5' flanking region of the insulin gene may affect expression of the gene and thereby modulate insulin production in severely obese female subjects.
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PMID:Central obesity and hyperinsulinaemia in women are associated with polymorphism in the 5' flanking region of the human insulin gene. 135 60

The metabolic syndrome (syndrome X) is characterised by an association of elevated insulin levels, a tendency to obesity of the android type, a disturbance of lipid metabolism with elevated triglyceride levels and commonly associated hypertension. The underlying common cause of this syndrome appears to be insulin resistance of the skeletal muscles, which is related in particular to the non-oxidative glucose utilization on the part of the muscle. The molecular cause of this syndrome has not been clarified, but a defect in the signal transduction chain between the insulin receptor and glycogen synthase is suspected. Epidemiological studies have shown that the metabolic syndrome may be considered a preliminary stage of manifest type II diabetes. In addition, it appears to play a major role in the development of cardiovascular complications in certain high-risk groups.
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PMID:[Pathophysiologic principles of metabolic syndrome. Consequences for early diagnosis and prevention]. 148 14

By the term "insulin resistance" we understand the attenuation of insulin-stimulated glucose uptake, which is mainly due to attenuated glycogen synthesis in skeletal muscle and is partially compensated with regard to plasma glucose homeostasis by hyperinsulinemia. Other mechanisms of insulin are either not attenuated or are less so and may contribute via hyperinsulinemia to the prevalence of hypertension, obesity, dyslipoproteinemia and type-II diabetes. At the level of insulin receptors, resistance can be due to muscle-specific, preferential expression of the low-affinity B-isoform of the insulin receptors. In rare cases of extreme resistance, it can also be due to several mutations at the insulin receptor gene or due to insulin-receptor autoantibodies. At the postreceptor level, the translocation and or expression of the insulin-responsive glucose carrier GluT-4 can be down-regulated via the hexosamine pathway by hyperglycemia plus hyperinsulinemia. Furthermore, Glut-4 can be inhibited and/or down-regulated by sustained insulin deficiency, partially via c-AMP-dependent pathways. Additionally, the insulin-induced glycogen synthesis in skeletal muscle can be attenuated by the endogenous peptides amylin and calcitonin-gene-related peptide, and by modulations of endothelial function, perfusion and capillary recruitment in the microcirculation of skeletal muscle. Epidemiological data indicate a genetic predisposition for insulin resistance. However, among the many mechanisms potentially contributing to the complex syndrome of insulin resistance, no specific localization of that predisposition can be proposed at present.
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PMID:[The mechanisms of insulin resistance]. 153 3

The present study was conducted to assess the effect of chromium (Cr) administration on glucose tolerance in insulin-dependent diabetes that accompanies hypertension. Four rat groups were used: stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) with and without streptozotocin (SZ, 40 mg/kg)-induced diabetes. Each group of rats was subdivided to the Cr-dose group and the control group. The Cr-dose group, which was intraperitoneally administered Cr solution (20 micrograms trivalent chromium/kg body weight/d for 4 weeks), and the control group (saline) were studied for plasma glucose and plasma insulin during intraperitoneal glucose tolerance test (IPGTT) and insulin action by isolated adipocytes. For diabetic SHRSP showing the highest plasma glucose and lowest plasma insulin among the four groups, Cr administration led to the greatest reduction in plasma glucose without a significant effect on plasma insulin during IPGTT. For each diabetic WKY and normal SHRSP and WKY, those given Cr showed lower levels of plasma glucose with lower levels of plasma insulin than the controls. For diabetic SHRSP, glucose uptake by isolated adipocytes in the Cr-dose group was higher than that in the control group. This effect of Cr administration involved enhancement of insulin responsiveness and sensitivity, attributed to enhanced affinity of the insulin receptor. A similar tendency was observed for diabetic WKY. However, for normal SHRSP and WKY, the increase in glucose uptake due to Cr administration coincided only with enhanced insulin responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chromium administration on glucose tolerance in stroke-prone spontaneously hypertensive rats with streptozotocin-induced diabetes. 164 Aug 49

Hyperandrogenism and lipid metabolism were shown to be related intimately. Any discussion of the nature of their relationship must include other clinical and metabolic variables such as hyperinsulinemia and UBO. Despite the many correlations among each of these factors, the appropriate sequence in the pathogenesis of these conditions has not been defined. Do conditions that result in insulin resistance (e.g., genetic defects, insulin receptor antibodies, and obesity) also lead to the development of hyperandrogenemia by direct or indirect ovarian stimulation by insulin? Does hyperandrogenism of ovarian or adrenal origin cause abnormal upper body fat distribution, in turn leading to lipid abnormalities and insulin resistance? Regardless of the issue of mechanism of causality, women with hyperandrogenism are thought to be at greater risk for cardiovascular morbidity and mortality than their normoandrogenic counterparts. These women often are obese, hypertensive, and sedentary; ingest diets high in saturated fats; and have glucose intolerance and/or insulin resistance. All these abnormalities are well known independent risk factors for the development of lipid abnormalities and cardiovascular disease. Whether hyperandrogenism is a secondary consequence of any of these or whether it is an independent contributor to lipid aberrations requires future study. Treatment strategies for hyperandrogenic women, however, should not only be directed toward alleviation of the cosmetic problem of hirsutism but also toward the prevention and treatment of cardiovascular morbidity using modalities aimed at eradicating hyperinsulinemia, hypertension, and dyslipidemia. These modalities should include modifications in diet, exercise, and weight in addition to pharmacologic and/or surgical manipulation. Weight reduction will reduce many cardiovascular risk factors. Obesity is easier to target because of the many risk factors that result in it.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipid metabolism and hyperandrogenism. 177 28

Insulin regulates cellular metabolic reactions by its action on the plasma membrane, intracellular enzymes and the nucleus. The first stage in the propagation of the insulin signal is the coupling of insulin to specific receptors at the cell surface. The exact mechanism whereby the transmembrane signalling mechanism (s) results in different insulin-mediated cellular effects is not known. However, the insulin receptor tyrosine kinase, the expression of second messengers, and the action of protein kinase C may, either individually or in combination, mediate some of the insulin effects, such as translocation and activation of glucose transporter proteins. Insulin resistance in clinical conditions such as insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), hypertension and obesity may be acquired to a large extent, and is thus partially reversible. Regulatory factors in insulin sensitivity, such as free fatty acids, counterregulatory hormones and blood glucose level, play an important role in the metabolic control and pathogenesis of insulin resistance in man.
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PMID:Regulation of insulin action at the cellular level. 204 21

Toxemia of pregnancy is a perplexing clinical problem that has defied accurate elucidation of its etiology because the disorder does not occur in undisturbed lower mammalian species that are currently used as animal models of reproductive physiology. We propose that toxemia of pregnancy occurs as the end stage human fetal-placental unit response to decreased maternal uterine blood flow, and that this fetal-placental unit response may be unique to the human species. The human fetus increases insulin secretion in response to progressive intrauterine asphyxia, which may result in decreased fetal-placental prostacyclin production (a vasodilator and inhibitor of platelet aggregation) and increased fetal-placental thromboxane A2 production (a vasoconstrictor). This could result in increased uteroplacental perfusion pressure, maternal hypertension, and increased maternal platelet aggregation. We also suggest that women who develop idiopathic toxemia of pregnancy are at increased risk for adult onset diabetes later on in life because they have a mild derangement in glucose-insulin homeostasis during their reproductive years that results in increased uterine vascular damage, that leads to decreased uterine blood flow, and ultimately the fetal hyperinsulinemia-prostaglandin pressor release mechanism. Therefore, prevention of toxemia may be possible by correction of mild derangements in glucose-insulin receptor homeostasis before conception occurs.
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PMID:Theory of the etiology of human toxemia of pregnancy: fetal hyperinsulinemia as a compensatory response to decreased uterine blood flow. 330 29

Although insulin resistance often occurs in association with hypertension, considerable variation is observed in the degree of insulin resistance among hypertensive patients. Since there is evidence of a genetic basis in the development of insulin resistance in hypertension, we analyzed the contribution of genetic factors to insulin resistance in hypertensive patients. Sixty-six Japanese hypertensive patients were studied. These patients were divided into two groups (hyperinsulinemia group and normoinsulinemia group) according to plasma insulin response during a 75-g oral glucose tolerance test (75g-OGTT). Insulin receptor gene (INSR) was studied for association with insulin resistance in hypertensive patients. A microsatellite polymorphism in intron-2 of the insulin receptor gene was analyzed by the polymerase chain reaction method. Five alleles were detected in the INSR microsatellite. The frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the normoinsulinemia group (73% vs. 43%, p = 0.02). There was no difference in genotype frequency of INSR between hypertensive patients and control subjects. When the hypertensive patients were divided into two groups, the frequency of C/C genotype in the hyperinsulinemia group was significantly higher than that in the control group (73% vs. 45%, p = 0.014). There was no significant difference between the normoinsulinemia group and control group. These data suggest that the insulin receptor gene may contribute to insulin resistance in hypertensive patients with hyperinsulinemia.
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PMID:Insulin receptor gene polymorphism and hyperinsulinemia in hypertensive patients. 758 31

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


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