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Biomedical subjects

Y Harano

Publications and source records attributed to Y Harano.

At least 37 records · Page 2Linked to original sources
PubMed1997

Identification and nitrogen regulation of the cyanase gene from the cyanobacteria Synechocystis sp. strain PCC 6803 and Synechococcus sp. strain PCC 7942.

An open reading frame (slr0899) on the genome of Synechocystis sp. strain PCC 6803 encodes a polypeptide of 149 amino acid residues, the sequence of which is 40% identical to that of cyanase from Escherichia coli. Introduction into a cyanase-deficient E. coli strain of a plasmid-borne slr0899 resulted in expression of low but significant activity of cyanase. Targeted interruption of a homolog of slr0899 from Synechococcus sp. strain PCC 7942, encoding a protein 77% identical to that encoded by slr0899, resulted in loss of cellular cyanase activity. These results indicated that slr0899 and its homolog in the strain PCC 7942 represent the cyanobacterial cyanase gene (designated cynS). While cynS of strain PCC 6803 is tightly clustered with the four putative molybdenum cofactor biosynthesis genes located downstream, cynS of strain PCC 7942 was found to be tightly clustered with the two genes located upstream, which encode proteins similar to the subunits of the cyanobacterial nitrate-nitrite transporter. In both strains, cynS was transcribed as a part of a large transcription unit and the transcription was negatively regulated by ammonium. Cyanase activity was low in ammonium-grown cells and was induced 7- to 13-fold by inhibition of ammonium fixation or by transfer of the cells to ammonium-free media. These findings indicated that cyanase is an ammonium-repressible enzyme in cyanobacteria, the expression of which is regulated at the level of transcription. Similar to other ammonium-repressible genes in cyanobacteria, expression of cynS required NtcA, a global nitrogen regulator of cyanobacteria.

Amino Acid Sequence↗
PubMed1997

Insulin resistance as an independent risk factor for carotid artery wall intima media thickening in vasospastic angina.

Studies have shown the presence of insulin resistance together with compensatory hyperinsulinemia in vasospastic angina as well as obstructive coronary artery disease. There is growing evidence that the development of coronary atherosclerosis may be closely related to systemic atherosclerosis as well as coronary spasm. However, no information is available about the possible relationship between insulin resistance and the existence of carotid atherosclerosis in vasospastic angina without segmental stenosis or luminal irregularities in coronary angiograms. To evaluate the independent effect of insulin resistance on carotid intima media thickening, we performed insulin sensitivity tests (steady-state plasma glucose method) on 40 patients with vasospastic angina and 24 control subjects with angiographically intact coronary arteries. Both oral glucose tolerance tests and lipid analyses were performed. Using B-mode ultrasonography, we assessed intima media thickness and plaque formation of common carotid arteries in these subjects. The steady-state plasma glucose level in the vasospastic angina group was about twofold higher than that of the control group, confirming the presence of insulin resistance in patients with vasospastic angina. The patients with vasospastic angina showed a significant increase in the average intima media thickness of the carotid wall and frequency of plaque formation, although they were comparable to the control subjects in risk factors other than insulin resistance. The intima media thickness was correlated with age (r = .62, P < .001), 2-hour insulin area (r = .45, P < .01), and steady-state plasma glucose level (r = .68, P < .0001) in patients with vasospastic angina. Similar correlations were observed in the control subjects. Multiple regression analyses of data indicated that 67% of the variation in the intima media thickness could be accounted for by age, steady-state plasma glucose level, and cigarette-years in vasospastic angina. In addition, differences in IMT were independently related to vasospastic angina. These results suggest that insulin resistance in association with compensatory hyperinsulinemia may be an important pathogenic factor for the development of coronary artery spasms and systemic early atherosclerosis.

Adult↗
PubMed1996

Lipoprotein analyses in patients with stable angina and acute coronary syndrome.

We have performed lipid analyses by using a table-top ultracentrifuge based on the Hatch and Lees' method in 77 subjects (60 men, 17 women: mean age, 63 years) to clarify lipoprotein disorders in coronary artery disease. Sixty-four subjects had coronary artery disease and 13 normal subjects were controls. They were divided into the groups with stable angina pectoris and with unstable angina pectoris or acute myocardial infarction (acute coronary syndromes). In patients with coronary artery disease, there were no significant differences from control in age, body mass index, total cholesterol, however, HDL cholesterol was significantly lower than those in the controls. LDL cholesterol:LDL apoB ratio, which is thought to reflect the size of LDL in coronary artery disease, was significantly smaller than that in the controls; mean values were 1.2 in coronary artery disease and 1.4 in controls. There were no significant differences in those lipoprotein disorders between the patients with stable angina and those with acute coronary syndromes. Though these lipoprotein abnormalities would not play a trigger role in acute coronary syndrome, they are characteristic of the lipid profile of patients with coronary artery disease.

Aged↗
PubMed1996

Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in nondiabetic hyperinsulinemic subjects.

This study was undertaken to investigate the effect of voglibose, a new alpha-glucosidase inhibitor, on glucose and lipid metabolism in nondiabetic hyperinsulinemic subjects. Sixteen nondiabetic subjects with hyperinsulinemia participated in the study. They were divided into two groups of eight subjects with normal (NGT) and impaired (IGT) glucose tolerance. A meal tolerance test and a 75-g oral glucose tolerance test (OGTT) were performed at the beginning (baseline phase) and end (treatment phase) of the 12-week treatment. Serum lipid levels were measured every 4 weeks throughout the treatment phase and follow-up phase (8 weeks). All patients received 1 0.2-mg tablet of voglibose before each test meal (3 tablets per day). We also measured insulin sensitivity using a steady-state plasma glucose (SSPG) method in eight normotensive hyperinsulinemic subjects and in eight age- and body mass index (BMI)-matched control subjects before and after the drug treatment. Voglibose significantly decreased the responses of plasma glucose and insulin on the meal tolerance test. The area under the curve for 2-hour insulin during the 75-g OGTT decreased after treatment, whereas that for 2-hour glucose did not change before and after treatment. SSPG was reduced after treatment, indicating improvement of insulin sensitivity. Moreover, treatment with voglibose resulted in a significant decline of triglyceride level and an elevation of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. These values returned to near-baseline levels after the drug was discontinued. Consequently, we conclude that this agent not only has a direct hypoglycemic effect through decreased absorption of carbohydrate, but also a hypoinsulinemic and hypolipidemic effect via improved insulin sensitivity.

Blood Glucose↗
PubMed1996

Insulin resistance as an independent risk factor for carotid wall thickening.

It has been reported that insulin resistance is associated with essential hypertension and that an aggregation of risk factors-hypertension, dyslipidemia, and glucose intolerance-together with insulin resistance leads to the more frequent appearance of coronary artery disease. We examined the relation between early asymptomatic atherosclerosis and these risk factors in 72 nondiabetic subjects with essential hypertension (41 men, 31 women) aged 50 to 59 years. Intima-media thickness and plaque formation of the carotid artery were assessed by B-mode ultrasonography, and insulin sensitivity was measured by the steady-state plasma glucose method. Lipoprotein profile was analyzed by ultracentrifugation. The intima-media thickness of the common carotid artery significantly correlated with systolic pressure; mean blood pressure; steady-state plasma glucose, indicating insulin resistance; fasting insulin; area under the curve of plasma insulin and glucose; body mass index; apolipoprotein B; apolipoprotein B in low-density lipoprotein; lower ratio of cholesterol to apolipoprotein B of low-density lipoprotein; and decreased high-density lipoprotein cholesterol. By multiple regression analysis, steady-state plasma glucose was the strongest risk, followed by lower high-density lipoprotein and systolic pressure. These three factors accounted for 54.9% of all the risk for increased intima-media thickness of the common carotid artery. In conclusion, insulin resistance was the strongest risk factor for carotid intima-media thickness, followed by lower high-density lipoprotein cholesterol and hypertension. An effort to maintain normal insulin sensitivity is essential for the prevention of early atheromatous lesions in essential hypertension.

Arteriosclerosis↗
PubMed1996

Role of insulin resistance associated with compensatory hyperinsulinemia in ischemic stroke.

BACKGROUND AND PURPOSE: Although insulin resistance and hyperinsulinemia play a crucial role in the pathogenesis of atherosclerosis, little is known about their roles in ischemic stroke. The purpose of this study was to clarify whether insulin resistance and hyperinsulinemia are causative factors in the pathogenesis of ischemic stroke. METHODS: Thirty-four consecutive patients with ischemic stroke, who were normotensive, nondiabetic, and not obese, were classified into three groups--atherothrombotic infarction (n = 16), lacunar infarction (n = 10), and cardioembolic infarction (n = 8)--based on clinical findings, brain imaging, and cerebral angiography. Both oral glucose tolerance tests and lipid analyses were performed. Insulin sensitivity was determined by the steady state plasma glucose method with the use of octreotide acetate. Data were compared with those of healthy control subjects (n = 15). RESULTS: Steady state plasma glucose levels were significantly higher in the atherothrombotic infarction group compared with control subjects and the other two stroke groups, indicating the presence of insulin resistance in patients with atherothrombotic infarction. In the atherothrombotic infarction group, the 2-hour insulin area (area under the plasma insulin concentration curve) during a 75-g oral glucose tolerance test was significantly increased and dyslipidemic changes (increased triglyceride and apolipoprotein B, decreased high-density lipoprotein) were observed, whereas these changes were not found in the lacunar infarction and cardioembolic stroke groups. CONCLUSIONS: Insulin resistance in association with compensatory hyperinsulinemia and dyslipidemia may be an important pathogenetic factor underlying the development of atherothrombotic infarction.

Aged↗
PubMed1996

Clinical impact of insulin resistance syndrome in cardiovascular diseases and its therapeutic approach.

In subjects with coronary artery diseases (obstructive and vasospastic angina pectoris (AP)) who have no diabetes, hypertension, obesity and physical inactivity, insulin sensitivity was significantly reduced with compensated hyperinsulinemia on OGTT. Insulin resistance significantly correlated with coronary atherosclerosis score. In vasospastic AP (VAP), those who fulfilled more than 3 risk factors out of 5 (hyperinsulinemia, obesity, glucose intolerance, hypertension, dyslipidemia) consist of 70 and 40% for smokers and nonsmokers respectively. Insulin resistance syndrome who fulfilled all the criteria was 9-10% for VAP. In atherothrombotic brain infarction (ATTI) with the same exclusion criteria, the similar insulin resistance and hyperinsulinemia have been observed, but not in embolic (cardiac origin) or lacunar infarction. In ATTI, high TG and apo B with low HDL-chol were noted in blood. In essential hypertension without diabetes and obesity, hyperinsulinemia was noted in 25-35% and insulin resistance in 56-88%. Reduction of blood pressure with alpha blocker (bunazosin), ACE inhibitor (cilazapril), long-acting Ca++ blocker (amlodipine) significantly improved lowered insulin sensitivity. Insulin resistance rather than hyperinsulinemia is more closely associated with blood pressure. Cardiovascular diseases (vasospastic and obstructive AP, brain cortical artery diseases) are prone to develop diabetes because of insulin resistance and also promote the generation of cumulative risk factors resulting in a vicious cycle. Efforts to alleviate insulin resistance is crucial for the primary and secondary prevention of cardiovascular diseases.

Adrenergic alpha-Antagonists↗
PubMed1996

Modified method using a somatostatin analogue, octreotide acetate (Sandostatin) to assess in vivo insulin sensitivity.

In order to evaluate the steady state plasma glucose (SSPG) method by using a new somatostatin derivative, octreotide acetate (Sandostatin) instead of somatostatin that we had used for the insulin sensitivity test, we examined whether octreotide was able to suppress C-peptide (CPR), glucagon (IRG), and GH to a similar degree to that achieved with somatostatin. A total of 52 studies were performed in 45 essential hypertensive subjects and 7 healthy subjects. Octreotide was given subcutaneously in a does of 50 micrograms or 100 micrograms 10 min before the test (sc 50, sc 100 groups) or intravenously infused over 2 h (10 micrograms in bolus followed by a constant infusion, 50, 100, or 150 micrograms/2 h: i.v. 50, i.v. 100, i.v. 150 groups). In all of the groups the plasma immunoreactive insulin (IRI) concentration increased gradually after insulin injection and reached the steady state plasma insulin (SSPI) level between 40 and 60 microU/ml at 60 min through 120 min. Plasma CPR at 120 min was the most suppressed (by 67% of the basal level in i.v. 150 group during the study period), but on the other hand in both the sc 100 and i.v. 100 groups the plasma CPR concentration at 120 min was suppressed by nearly 40%, but not significantly suppressed in either the sc 50 or the i.v. 50 group. Plasma IRG and GH were strongly suppressed after 60 min in all groups during the study period. Plasma glucose had increased significantly at 30 min and reached the steady state at 90 min through 120 min in hypertensive and healthy subjects. The results indicated that the modified SSPG method with continuous intravenous infusion of Octreotide at 150 micrograms/2 h was adequate for the measurement of insulin sensitivity.

Blood Glucose↗
PubMed1996

Effects of simvastatin on the number and composition of apoproteinB-containing lipoproteins in hypercholesterolemia: analysis of apoproteinB in each lipoprotein fraction by highly sensitive latex method.

We investigated the effects of simvastatin on the number and composition of apoproteinB (apoB)-containing lipoproteins in thirteen patients with hypercholesterolemia type IIa or IIb by measuring apoB by a highly sensitive latex method. Patients received simvastatin 5-10 mg (7.7 +/- 0.7 mg, mean +/- SEM) daily for 83-218 days (131 +/- 13 days). In both types of patients, treatment with simvastatin significantly reduced plasma cholesterol levels (mean +/- SEM mg/dl: in type IIa from 234.4 +/- 5.4 to 171.4 +/- 7.8, in type IIb from 242.4 +/- 11.6 to 178.8 +/- 9.6), low density lipoprotein (LDL) cholesterol levels (from 122.6 +/- 5.2 to 68.5 +/- 4.6, and from 115.6 +/- 14.0 to 70.4 +/- 11.6 in the two types, respectively) and LDL apoB levels (from 94.5 +/- 6.6 to 60.6 +/- 7.0, and from 85.0 +/- 8.4 to 56.6 +/- 6.2, respectively). There was no significant change in cholesterol, triglyceride (TG) or apoB in very low density lipoprotein (VLDL). High density lipoprotein (HDL) cholesterol did not change in this study. With respect to lipoprotein composition, the ratio of either cholesterol or TG to apoB in VLDL, intermediate density lipoprotein (IDL) and LDL did not change significantly, but that of TG to apoB in the IDL fraction increased in type IIa. Simvastatin promotes more effective reduction in cholesterol and apoB in LDL than in VLDL, probably by increasing the hepatic LDL receptor which preferentially binds LDL.

Adult↗
PubMed1996

Risk factor analyses for macrovascular complication in nonobese NIDDM patients. Multiclinical Study for Diabetic Macroangiopathy (MSDM).

To examine the characteristic features of risk factors for macroangiopathy (MA) in nonobese Japanese NIDDM patients, 899 NIDDM patients with and without MA were registered from 40 facilities. Of these, 386 subjects were identified as having any form of MA (total MA); these included 211 with ischemic heart disease (IHD), 163 with cerebrovascular disease (CVD), and 77 with peripheral vascular disease (PVD). Univariate analyses revealed the following common risk factors for total MA, IHD, CVD, and PVD: age, hypertension, systolic blood pressure (sBP) or diastolic blood pressure (dBP), duration of diabetes, diabetic microangiopathy (retinopathy, nephropathy, and neuropathy), low HDL cholesterol level, and higher LDL cholesterol/HDL cholesterol ratio. Additional significant risk factors for specific conditions were also identified, respectively, as male sex for total MA, IHD, and PVD, smoking for IHD and PVD, and high fasting plasma glucose level for total MA and CVD. With stepwise multivariate logistic regression analysis, older age, duration of diabetes, smoking, and low LDL cholesterol/HDL cholesterol ratio were identified as significant and independent risk factors for total MA, IHD, CVD, and PVD. Other risk factors identified were high dBP for IHD, CVD, and PVD, high sBP for total MA, and low BMI for PVD. These results clearly demonstrated that duration of diabetes, smoking, hypertension, and dyslipidemia are major risk factors for MA in NIDDM patients. Since the mean BMI was similar for both groups (approximately 23 kg/m2) and there were no significant differences in immunoreactive insulin levels before and after 75-g oral glucose challenge testing, obesity and hyperinsulinism at the time of the analyses were not considered to play an important role for the pathogenesis of MA in Japanese NIDDM patients. By using the chi 2 test, cutoff points were determined for six of the most commonly measured risk factors. The cutoff point was the level beyond which a significantly higher prevalence of MA occurred. The cutoff points (rounded slightly upward in some cases) for fasting plasma glucose, sBP, dBP, serum total cholesterol level, serum triglyceride level, and BMI were 140 mg/dl, 140 mmHg, 80 mmHg, 180 mg/dl, 120 mg/dl, and 23 kg/m2, respectively. When these cutoff points were used as control criteria, the prevalence of MA was significantly lower in subjects whose risk factor measurements remained under the proposed control criteria for four or more of the six variables. In conclusion, in nonobese NIDDM patients, age, hypertension, and dyslipidemia were found to be risk factors for MA. Duration of diabetes was also demonstrated as an independent risk factor, indicating the close association of deranged glucose metabolism with the pathogenesis of MA in NIDDM patients. It seems to be crucial to control these risk factors for the prevention of MA in NIDDM patients.

Aged↗
PubMed1996

Quantitative and qualitative derangement of apolipoprotein B-containing lipoproteins as a risk factor for diabetic macroangiopathy in nonobese NIDDM subjects.

Cholesterol, triglyceride (TG), and apolipoprotein (apo) B were determined in plasma and in lipoprotein subfractions (VLDL, intermediate-density lipoproteins [IDL], LDL, and HDL) in nonobese NIDDM subjects, who were classified into well-controlled, fairly controlled, or poorly controlled states with or without macrovascular complications (macroangiopathy [MA]). The same analyses were also performed on subjects who had coronary artery disease (CAD) with stable angina pectoris (SA) or unstable angina pectoris (UA) and acute myocardial infarction, cerebrovascular disease (CVD) with atherothrombotic or lacunar infarction, and arteriosclerosis obliterans (ASO). In nonobese NIDDM subjects, the number of apoB-containing lipoproteins (VLDL, IDL, and LDL) increased. This alteration was more prominent in subjects with poorly or fairly controlled disease as well as in subjects with MA, but not in those with well-controlled NIDDM. Cholesterol/apoB in LDL decreased in subjects with poorly or fairly controlled diabetes or with MA and was correlated with low HDL cholesterol. The disorder is characterized by hyperbetalipoproteinemia with elevated LDL cholesterol and small dense LDL. In obese NIDDM subjects, the similar disorder was more pronounced. Glycemic control had less effect and hyperinsulinemia, if present, aggravated the lipid disorder. In those with CAD, the number of IDLs increased and the LDL fraction had the properties of small dense LDL. HDL cholesterol decreased. In those with UA, the LDL number increased without elevation of LDL cholesterol, indicating typical hyperbetalipoproteinemia. The subjects with atherothrombotic brain infarction, an increased number of small-sized LDLs was noted. In those with ASO, the number of VLDL and IDL increased with small LDL. HDL cholesterol decreased in those with CAD, cerebrovascular disease, and ASO. Since similar quantitative and qualitative alterations of apoB-containing lipoprotein have been observed in NIDDM patients as well as in those with macrovascular diseases, diabetic patients are thought to be more susceptible to the initiation and progression of atheromatous lesions in coronary, brain, and peripheral arteries.

Adult↗
PubMed1996

Mechanism and clinical implication of insulin resistance syndrome.

The insulin resistance syndrome has been noted as an interesting and important new risk factor for coronary artery disease. The syndrome consists of hypertension, glucose intolerance, and dyslipidemia, all of which are likely to be derived from insulin insensitivity. In subjects with nonobese and nondiabetic essential hypertension, steady-state plasma glucose (SSPG) was higher than in normotensive subjects during an insulin sensitivity test, indicating reduced insulin sensitivity to glucose metabolism in the hypertensive group. SSPG correlated with the percentage decrease of branched chain amino acids, free fatty acids, and serum potassium during the insulin sensitivity test. With a 2-h insulin infusion, serum norepinephrine, epinephrine, plasminogen activator inhibitor 1, and intraplatelet Ca2+ decreased significantly, but 6-keto-prostaglandin (PG) F1 alpha and PGE2 did not change. Insulin resistance decreased by using antihypertensive treatments with bunazosin, cilazapril, amlodipine, and benidipine in hypertensive subjects. Diagnostic criteria for the insulin resistance syndrome, including clinical values for each risk factor, were developed. Lowered insulin sensitivity and hyperinsulinemia were demonstrated in subjects with both vasospastic and coronary artery stenotic angina. The insulin resistance syndrome together with hyperinsulinemia is likely to induce atherosclerotic changes, possibly through reduced rather than excessive action of insulin.

Angina Pectoris↗
PubMed1996

Demonstration of insulin resistance in coronary artery disease documented with angiography.

OBJECTIVE: To evaluate the relation between insulin resistance and coronary atherosclerosis, insulin sensitivity in lean nondiabetic, normotensive subjects with and without obstructive coronary artery disease (CAD). The correlation between insulin resistance and degree of coronary stenosis was also investigated. RESEARCH DESIGN AND METHODS: Four groups were studied: 1) nine subjects with normal glucose tolerance (NGT) without CAD, 2) 10 subjects with NGT with CAD, 3) nine subjects with impaired glucose tolerance (IGT) without CAD, and 4) 10 subjects with IGT with CAD. Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method using Sandostatin. Coronary angiography was performed in all study subjects, and the severity of coronary artery atherosclerosis was quantified in a modified Gensini score. RESULTS: The SSPG (millimoles per liter) levels were significantly higher in the patients with CAD compared with control subjects (control vs. patient group: 4.8 +/- 0.5 vs. 7.9 +/- 0.9 with NGT, P < 0.05; 5.6 +/- 0.5 vs. 11.1 +/- 0.8 with IGT, P < 0.001), indicating the presence of insulin resistance in patients with CAD. The coronary atherosclerosis score (CAS) was significantly and positively correlated with SSPG (r = 0.74, P < 0.05) and 2-h insulin area (r = 0.78, P < 0.01) in NGT subjects with CAD. On the other hand, the percentage fall of plasma free fatty acid (0-30 min) during an insulin sensitivity test was significantly decreased in the subjects with CAD and was inversely correlated with the CAS (r = -0.43, P < 0.05), especially in NGT subjects with CAD. CONCLUSIONS: These data suggest that in patients with CAD, insulin-mediated glucose metabolism is significantly impaired, and a significant correlation was noted between insulin resistance and severity of CAD. Therefore, the hyperinsulinemia often observed in patients with CAD is attributable to the compensatory mechanism of the beta-cell to the inadequate action of insulin for glucose metabolism. Hyperinsulinemia in the presence of insulin resistance aggravates dyslipidemia and may stimulate the atheromatous process by an as-yet-unknown mechanism.

Adult↗
PubMed1995

Insulin resistance associated with compensatory hyperinsulinemia as an independent risk factor for vasospastic angina.

BACKGROUND: It is generally believed that coronary artery spasm plays an important role in the progression of obstructive coronary artery disease. Since insulin resistance together with hyperinsulinemia plays an important role in the pathogenesis of coronary atherosclerosis, we investigated the association of hyperinsulinemia and insulin resistance with vasospastic angina (VAP). METHODS AND RESULTS: The study population consisted of 60 patients with VAP and 42 control subjects (62 subjects with normal glucose tolerance and 40 with impaired glucose tolerance). Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method for nondiabetic, normotensive, nonobese subjects (16 control subjects, 16 obstructive coronary artery disease patients, and 16 VAP patients). Compared with the control group, the 2-hour insulin area (area under the plasma insulin concentration-time curve) during a 75-g oral glucose tolerance test was significantly higher in both VAP groups with normal and impaired glucose tolerance. A high frequency of vasospastic angina was observed in subjects with clustered risk factors for insulin resistance syndrome, suggesting a close association of VAP with this syndrome. In stepwise discriminant analysis, the 2-hour insulin area was significantly associated with VAP independent of other risk factors. SSPG level in VAP was about twofold over control, indicating the presence of insulin resistance in patients with VAP. However, no differences were found between patients with VAP and obstructive coronary artery disease with respect to mean SSPG level. CONCLUSIONS: SSPG level was significantly elevated in patients with VAP and obstructive coronary artery disease compared with control subjects. This indicates that hyperinsulinemia is secondary to insulin resistance, both of which are thought to play important roles as risk factors for VAP in the early atheromatous lesion and in the future development of occlusive lesions when chronically present.

Angina Pectoris, Variant↗
PubMed1995

Improvement of insulin sensitivity for glucose metabolism with the long-acting Ca-channel blocker amlodipine in essential hypertensive subjects.

To clarify whether the long-acting calcium-channel blocker amlodipine restores insulin insensitivity in essential hypertension, insulin sensitivity tests were performed at the physiological steady-state insulin level (45 to 55 microU/mL) before and after amlodipine (2.5 to 7.5 mg/d) administration for 2 to 4 months in borderline and mild essential hypertensive subjects. Instead of somatostatin, Sandostatin (Sandoz, Basel, Switzerland) was used for the determination of steady-state plasma glucose (SSPG) in the same way as previously described. SSPG, which was initially high (212.9 +/- 18.0 mg/dL, mean +/- SE), was significantly reduced to 169.8 +/- 14.7 after amlodipine treatment. Responses of ketone bodies during the test at 30 minutes, which reflect the insulin effect on lipolysis in adipose tissue and hepatic fatty acid oxidation, also improved after amlodipine treatment. Norepinephrine, noted to be mildly elevated after amlodipine treatment, decreased during the sensitivity test at 2 hours probably due to the sedative effect, without any change in the fractional extraction of Na. This indicates that the physiological level of insulin does not activate sympathetic nerve activity or stimulate Na reabsorption. The long-acting calcium-channel blocker amlodipine has significantly improved the initially decreased insulin sensitivity for glucose metabolism at least partially in borderline or mild essential hypertension.

Amlodipine↗
PubMed1995

Normalization of insulin resistance in non-obese essential hypertension by cilazapril treatment.

To determine whether ACE inhibitor other than captopril improves insulin sensitivity in patients with essential hypertension, we measured insulin sensitivity to glucose utilization using SSPG method in 10 lean hypertensive subjects before and after chronic cilazapril treatment (1.5 +/- 0.2 mg/day, 15.6 +/- 2.1 weeks). The results were compared with those obtained in 10 healthy control subjects. SSPG obtained by insulin sensitivity test was significantly higher in hypertensive subjects, indicating a lower insulin sensitivity than in controls. After cilazapril treatment, SSPG reduced significantly to the level which was statistically not different from control subjects. Hyperinsulinemia diminished after treatment, while no significant change of blood glucose was observed during oral glucose tolerance test in hypertensive subjects. Plasma HDL cholesterol increased by cilazapril treatment. Cilazapril treatment has beneficial effect in the reversal of insulin resistance in patients with essential hypertension.

Antihypertensive Agents↗
PubMed1995

Insulin resistance rather than hyperinsulinemia more closely associated with essential hypertension.

In order to clarify which of the two, insulin resistance or hyperinsulinemia, are more contributable to non obese and non diabetic hypertension, insulin sensitivity test was performed. By multiple regression analysis, mean, systolic, and diastolic blood pressure were inversely correlated with glucose clearance. During insulin sensitivity test, plasma catecholamines levels and FENa were not changed by insulin infusion. In the present study, it is demonstrated that insulin has no hypertensive effect under the mild hyperinsulinemia (45-55 microU/ml). We conclude that insulin resistance rather than hyperinsulinemia may be more closely associated with non obese and non diabetic hypertension.

Analysis of Variance↗