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Y D Chen

Publications and source records attributed to Y D Chen.

At least 19 recordsLinked to original sources
PubMed1995

Kinetics of binding of caldesmon to actin.

The time course of interaction of caldesmon with actin may be monitored by fluorescence changes that occur upon the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or to acrylodan actin. The concentration dependence of the observed rate of caldesmon-actin binding was analyzed to a first approximation as a single-step reaction using a Monte Carlo simulation. The derived association and dissociation rates were 10(7) M-1 s-1 and 18.2 s-1, respectively. Smooth muscle tropomyosin enhances the binding of caldesmon to actin, and this was found to be due to a reduction in the rate of dissociation to 6.3 s-1. There is no evidence from this study for a different mechanism of binding in the presence of tropomyosin. The fluorescence changes that occurred with the binding of 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-labeled caldesmon to actin or actin-tropomyosin were reversed by the addition of myosin subfragment 1 as predicted by a competitive binding mechanism.

Actins↗
PubMed1995

Generation of antibodies against a human lipoprotein lipase fusion protein.

Antibodies generated against specific proteins are useful tools for studying the physiology and cell biology of the protein of interest. Although antibodies have been successfully generated against lipoprotein lipase (LPL) and used to elucidate many aspects of its biology, there have been problems with the specificity, affinity and availability of these antibodies. To circumvent these problems, we have expressed a portion of human LPL as a bacterial fusion protein. The human LPL bacterial fusion protein was utilized to generate polyclonal antibodies in rabbits that recognize intact human, rat and bovine LPL. Using these antibodies, it was possible to demonstrate a direct correlation between LPL mass and LPL activity from different samples of human post-heparin plasma. In addition, these antibodies were used to develop an ELISA for the measurement of LPL in tissue or plasma. This is a useful means for obtaining polyclonal antibodies to LPL in sufficient quantity and without contaminating mammalian proteins.

Animals↗
PubMed1995

Comparison of the hemodynamic and metabolic effects of low-dose hydrochlorothiazide and lisinopril treatment in obese patients with high blood pressure.

Patients with high blood pressure tend to be insulin resistant, glucose intolerant, hyperinsulinemic, and dyslipidemic. Since these metabolic defects are accentuated by obesity, we thought it important to compare the effects of 3 months' treatment with either lisinopril (20 mg/day) or low dose hydrochlorothiazide (12.5 mg/day) on blood pressure and glucose, insulin, and lipoprotein metabolism in obese patients with hypertension. There were 14 patients in each group, and they were similar (mean +/- SE) in age (54 +/- 3 v 50 +/- 4 years), gender (nine men/five women), and body mass index (33.4 +/- 0.8 v 33.9 +/- 0.9 kg/m2). Patients treated with lisinopril had a somewhat greater fall in both systolic (18 +/- 3 v 10 +/- 3 mm Hg) and diastolic (12 +/- 2 v 8 +/- 1 mm Hg) blood pressure, but only the change in systolic pressure was statistically significant (P < .05). Plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at 12 PM), and there was a modest increase in all three variables following hydrochlorothiazide treatment (P < .05 to P < .09). However, daylong plasma glucose, insulin, and triglyceride concentration did not change with lisinopril treatment. Finally, neither the ability of insulin to mediate glucose disposal nor fasting lipid and lipoprotein concentrations, changed with either treatment. In conclusion blood pressure decreased significantly following treatment with either lisinopril (20 mg/day) or hydrochlorothiazide (12.5 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Effect of weight loss on blood pressure and insulin resistance in normotensive and hypertensive obese individuals.

In this study, the effect of weight loss on blood pressure and various facets of glucose and insulin metabolism was examined in 22 subjects with mild to moderate obesity; 11 with high blood pressure (diastolic blood pressure > 95 mm Hg) and 11 with normal blood pressure (diastolic blood pressure < 90 mm Hg). The two groups were similar in mean (+/- SEM) body mass index at baseline (30.2 +/- 1.0 v 31.6 +/- 1.1 kg/m2), and each group lost approximately 8 kg during the 3-month study period. Blood pressure fell significantly (P < .003) following the 8 kg weight loss in both the normotensive (122 +/- 3/81 +/- 3 to 110 +/- 3/74 +/- 2 mm Hg) and hypertensive (149 +/- 3/98 +/- 1 to 135 +/- 3/86 mm Hg) subjects. Furthermore, the plasma glucose and insulin responses to a 75 g oral glucose load were significantly lower (P < .001) following weight loss. Finally, insulin resistance, as assessed by determining the steady-state plasma glucose (SSPG) concentration at the end of a 180 min infusion of somatostatin, insulin, and glucose, was also lower (P < .002) after the 8 kg weight loss in the normotensive (243 +/- 23 to 172 +/- 15 mg/dL) and hypertensive subjects (266 +/- 18 to 181 +/- 25 mg/dL). Since the steady-state plasma insulin concentrations were, if anything, slightly lower after weight loss in both groups, the lower post-weight loss SSPG values actually underestimate the improvement of insulin resistance. Thus, weight loss of 8 kg in moderately obese individuals leads to significant decreases in blood pressure and plasma glucose and insulin concentrations in response to an oral glucose challenge and degree of insulin resistance.

Adult↗
PubMed1995

Metabolic abnormalities following heart transplantation in patients with idiopathic cardiomyopathy.

The purpose of this study was to evaluate the risk factors for coronary artery disease associated with initiation of immunosuppressive therapy in patients with a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July 1992 to June 1993. All patients were treated with cyclosporine, azathioprine and prednisolone, and the following measurements were performed prior to hospital discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1) fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and insulin concentrations in response to a 75 g oral glucose challenge; and 3) steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI concentrations are similar in all individuals, the SSPG concentrations provide an estimate of the ability of insulin to stimulate glucose disposal. Only six of the patients had a normal oral glucose tolerance test and the following diagnoses were found in the remaining nine patients: not diagnised (n = 3), impaired glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma lipid and lipoprotein concentrations were also frequently abnormal in the heart transplant patients; eight of the 15 patients had a plasma cholesterol > 5 mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1 mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value rarely exceeded in healthy volunteers. In conclusion, significant metabolic abnormalities were present at discharge in patients who had undergone successful cardiac transplantation for idiopathic cardiomyopathy. These metabolic abnormalities were probably caused by the use of immunosuppressive drugs. Given the magnitude of these changes, it would seem prudent to initiate therapeutic programs in patients with cardiac transplants that are not simply aimed at preventing rejection, but also address the metabolic abnormalities associated with the immunosuppressive agents used to prolong allograft survival.

Adult↗
PubMed1995

Effect of variations in oral fat and carbohydrate load on postprandial lipemia.

In this study we assessed the acute effects of the consumption of varying amounts of fat and fructose on the magnitude of postprandial lipemia. Subjects were studied after an overnight fast on four separate mornings, ingesting in random order 5, 40, or 80 g fat, or 5 g fat plus 50 g fructose. Vitamin A (36 mg, or 120,000 U retinol) was also given and blood was drawn at frequent intervals over the next 10 h for measurement of triacylglycerol and retinyl palmitate (RP) concentrations in plasma and the Sf > 400 and Sf 20-400 lipoprotein fractions. (Sf denotes flotation units.) In general, the postprandial triacylglycerol response increased in plasma and in both lipoprotein fractions as a function of both the baseline fasting triacylglycerol concentration and the amount of fat ingested. However, no matter how high the fasting plasma triacylglycerol concentration, there was no increase in the postprandial triacylglycerol concentration in plasma or either lipoprotein fraction after the 5-g oral fat load. The results of the measurements of RP concentration were somewhat similar in that there was a dose-dependent increase in the plasma and the Sf > 400 lipoprotein fraction in response to the higher fat loads. However, just the opposite was true in the Sf 20-400 lipoprotein fraction, for which the increase in RP concentration was inversely related to the size of the fat load.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia.

We examined the relation between insulin resistance, plasma glucose and insulin responses to meals, lipoprotein lipase (LPL) activity, and postprandial lipemia in a population of 37 healthy nondiabetic individuals. Plasma glucose and insulin concentrations were determined at frequent intervals from 8 AM through midnight (breakfast at 8 AM and lunch at noon); resistance to insulin-mediated glucose disposal was determined by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of glucose, insulin, and somatostatin; LPL activity was quantified in postheparin plasma; and postprandial concentrations of triglyceride (TG)-rich lipoproteins were assessed by measuring the TG and retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20 to 400 lipoprotein fractions. Significant simple correlation coefficients were found between various estimates of postprandial lipemia and SSPG (r = .38 to .68), daylong insulin response (r = .37 to .58), daylong glucose response (r = .10 to .39), and LPL activity (r = -.08 to -.58). However, when multiple regression analysis was performed, only SSPG remained independently associated with both postprandial TG and retinyl palmitate concentrations. These data provide evidence that insulin resistance plays an important role in regulating the postprandial concentration of TG-rich lipoproteins, including those of intestinal origin.

Adult↗
PubMed1995

Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia.

Recent reports have shown that the frequency of the homozygous deletion genotype (DD) of the angiotensin-converting enzyme (ACE) gene is highly associated with myocardial infarction and cardiomyopathy, particularly in those considered to be at low risk for coronary heart disease (CHD) on the basis of their apoB or LDL cholesterol concentrations. The present study was initiated to extend this inquiry by exploring the possibility that the ACE/DD genotype might be associated with risk factors not evaluated in the initial reports. Consequently, we determined the ACE genotype in 181 subjects, 124 with normal glucose tolerance and 57 with noninsulin-dependent-diabetes mellitus (NIDDM), and compared various aspects of glucose, insulin, and lipoprotein metabolism in the three ACE genotypes. In general, normal subjects with the DD genotype had a lower body mass index, were more insulin sensitive (as assessed by the insulin suppression test), and had lower plasma glucose and insulin responses to oral glucose. In addition, plasma triglyceride and cholesterol concentrations were lowest and HDL cholesterol concentrations highest in the DD group. However, the only statistically significant differences were between the ID and DD groups; the latter had lower values for body mass index, was more insulin sensitive, and had a lower plasma insulin response to oral glucose. Similar but insignificant trends were noted in the patients with NIDDM. The present results show that subjects with the ACE/DD genotype are not at increased risk for CHD because of insulin resistance, relative hyperglycemia and hyperinsulinemia, or a dyslipidemia characterized by a high triglyceride and low HDL cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Relationship between insulin-mediated glucose disposal by muscle and adipose tissue lipolysis in healthy volunteers.

The present study was performed in 17 nondiabetic subjects and was initiated to determine whether enhanced adipose tissue lipolysis, either basal or catecholamine induced (isoproterenol), and/or resistance to insulin inhibition of isoproterenol-stimulated lipolysis were correlated with resistance to insulin-mediated glucose disposal by muscle. Insulin-mediated glucose disposal was assessed by determining the steady state plasma glucose (SSPG) concentration during the insulin suppression test [180 min infusion of somatostatin (350 micrograms/h), insulin (25 mU/m2min), and glucose (240 mg/m2.min)]. On another occasion, plasma FFA and glycerol concentrations were determined at the end of 3 sequential infusion periods (IP): IP1, somatostatin (350 micrograms/h) plus basal insulin replacement (5 mU/m2.min); IP2, somatostatin (350 micrograms/h), insulin (5 mU/m2.min), and isoproterenol (270 ng/m2.min); and IP3, somatostatin (350 micrograms/h), isoproterenol (270 ng/m2.min), and insulin (10 mU/m2.min). SSPG concentrations correlated with FFA concentrations during all 3 infusion periods after adjustment for age, gender, body mass index, insulin concentration, and ratio of waist to hip girth (IP1:r = 0.61; P < 0.03; IP2: r = 0.70; P < 0.01; IP3: r = 0.65; P < 0.02). Correlations between SSPG and glycerol concentrations were also highly statistically significant (IP1: r = 0.62; P < 0.03; IP2: r = 0.65; P < 0.02; IP3: r = 0.70; P < 0.01). These results demonstrate for the first time that plasma FFA and glycerol concentrations are increased commensurate with the degree of resistance to insulin-mediated glucose disposal at a basal insulin level, in response to isoproterenol stimulation, and after insulin inhibition of isoproterenol-stimulated lipolysis.

Adipose Tissue↗
PubMed1995

Why do low-fat high-carbohydrate diets accentuate postprandial lipemia in patients with NIDDM?

OBJECTIVE: To understand why low-fat high-carbohydrate (CHO) diets lead to higher fasting and postprandial concentrations of triglyceride (TG)-rich lipoproteins in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Patients with NIDDM were placed randomly on diets containing either 55% CHO, 30% fat, and 15% protein or 40% CHO, 45% fat, and 15% protein for 6 weeks, followed by crossover to the other diet. Test meals at the end of each diet period were consumed at 8:00 A.M. and 12:00 P.M. (noon) and contained 20 and 40% of daily calories, respectively. Vitamin A was also given at noon, and TG-rich lipoproteins of intestinal origin were identified by the presence of vitamin A esters. Frequent measurements were made throughout the 24-h study period of plasma glucose, insulin, and TG concentrations. Plasma samples obtained from 12:00 P.M. (noon) until 12 A.M. (midnight) were subjected to ultracentrifugation, and measurements were made of TG and vitamin A ester concentrations in plasma and in both the Svedberg flotation constant (Sf) > 400 (chylomicron) and Sf 20-400 (chylomicron remnant) lipoprotein fractions. In addition, very-low-density lipoprotein (VLDL)-TG turnover rate was estimated by following the decay of [3H]VLDL-TG. Finally, postheparin lipoprotein lipase and hepatic lipase activities were measured at the end of each dietary period. RESULTS: Mean +/- SE hourly concentrations of glucose (8.0 +/- 0.8 vs. 7.5 +/- 0.7 mmol/l), insulin (184 +/- 26 vs. 158 +/- 19 pmol/l), and TG (2.8 +/- 0.2 vs. 2.1 +/- 0.2 mmol/l) were higher (P < 0.05-0.001) after the 55% CHO diet. The 55% CHO diet also led to an increase (P < 0.05-0.01) in the mean +/- SE hourly concentrations of vitamin A esters in plasma (2.3 +/- 0.3 vs. 1.6 +/- 0.1 mumol/l) and in both the chylomicron (2.0 +/- 0.3 vs. 1.4 +/- 0.1 mumol/l) and chylomicron remnant fractions (0.36 +/- 0.04 vs. 0.14 +/- 0.03 mumol/l). In addition, the VLDL-TG production rate was higher (17.2 +/- 1.4 vs. 12.8 +/- 1.0 mg.kg-1.h-1, P < 0.003) and the VLDL-TG fractional catabolic rate lower (0.22 +/- 0.02 to 0.28 +/- 0.02 l/h, P < 0.005) after the 55% CHO diet. Finally, there was an increase in lipoprotein lipase activity (7.0 +/- 0.8 to 8.1 +/- 0.7 mumol free fatty acids released .ml-1.h-1, P < 0.02) in response to the CHO-enriched diet. CONCLUSIONS: A low-fat high-CHO diet in patients with NIDDM led to 1) higher day-long plasma glucose, insulin, and TG concentrations; 2) postprandial accumulation of TG-rich lipoproteins of intestinal origin; 3) increased production of VLDL-TG; and 4) increased postheparin lipoprotein lipase activity. These data provide a mechanism for the hypertriglyceridemic effect of CHO-enriched diets in patients with NIDDM and demonstrate that multiple risk factors for coronary heart disease are accentuated when these individuals consume diets recommended to reduce this risk.

Adult↗
PubMed1994

Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: A four-center randomized crossover trial. SETTING: Outpatient and inpatient evaluation in metabolic units. PATIENTS: Forty-two NIDDM patients receiving glipizide therapy. INTERVENTIONS: A high-carbohydrate diet containing 55% of the total energy as carbohydrates and 30% as fats was compared with a high-monounsaturated-fat diet containing 40% carbohydrates and 45% fats. The amounts of saturated fats, polyunsaturated fats, cholesterol, sucrose, and protein were similar. The study diets, prepared in metabolic kitchens, were provided as the sole nutrients to subjects for 6 weeks each. To assess longer-term effects, a subgroup of 21 patients continued the diet they received second for an additional 8 weeks. MAIN OUTCOME MEASURES: Fasting plasma glucose, insulin, lipoproteins, and glycosylated hemoglobin concentrations. Twenty-four-hour profiles of glucose, insulin, and triglyceride levels. RESULTS: The site of study as well as the diet order did not affect the results. Compared with the high-monounsaturated-fat diet, the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24% (P < .0001) and 23% (P = .0001), respectively, and increased daylong plasma triglyceride, glucose, and insulin values by 10% (P = .03), 12% (P < .0001), and 9% (P = .02), respectively. Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels remained unchanged. The effects of both diets on plasma glucose, insulin, and triglyceride levels persisted for 14 weeks. CONCLUSIONS: In NIDDM patients, high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable.

Adult↗
PubMed1994

Effect of glipizide treatment on postprandial lipaemia in patients with NIDDM.

The primary goal of the present study was to examine the effects of improved glycaemic control associated with glipizide treatment on postprandial lipaemia in non-insulin-dependent diabetic patients. The metabolism of triglyceride-rich lipoproteins of intestinal origin was assessed by measuring the retinyl palmitate content in plasma and the Svedberg flotation index (Sf) > 400 and Sf 20-400 lipoprotein fractions. Fasting plasma glucose concentrations (14.5 +/- 0.5 vs 9.0 +/- 0.5 mmol/l), glycated haemoglobin levels (13.1 +/- 0.6 vs. 9.7 +/- 0.6%), and daylong plasma glucose concentrations were all significantly lower after glipizide treatment (p < 0.001). The improvement in glycaemic control was associated with increases in insulin-mediated glucose uptake (p < 0.001) and plasma post-heparin lipoprotein and hepatic lipolytic activities (p < 0.02). Both fasting plasma triglyceride (3.09 +/- 0.51 vs 2.37 +/- 0.34 mmol/l), and postprandial triglyceride concentrations (p < 0.05-0.001) were lower following glipizide treatment, associated with a significant fall in retinyl palmitate content in all three lipoprotein fractions (p < 0.02-0.001), with the most substantial decrease seen in the Sf20-400 fraction. These data indicate that glipizide-induced improvement in glycaemic control was associated with changes in the metabolism of triglyceride-rich lipoproteins of intestinal origin that would be anticipated to reduce risk of coronary heart disease in non-insulin-dependent diabetic patients.

Blood Glucose↗
PubMed1994

Metabolic risk factors for atherosclerosis in heart transplant recipients.

Development of coronary artery disease (CAD) in the cardiac allograft limits long-term survival after heart transplantation. Previous studies, focusing on lipoprotein metabolism, have paid little attention to changes in glucose and insulin metabolism that increase the risk of CAD in these patients. To address this issue, plasma glucose and insulin responses to an oral glucose load and lipid and lipoprotein concentrations were measured in male normal volunteers (n = 40) and cardiac transplant recipients with pretransplant diagnoses of either idiopathic cardiomyopathy (n = 24) or ischemic heart disease (n = 28), matched for age and body mass index. Patients with a pretransplant diagnosis of ischemic heart disease had higher plasma glucose and insulin concentrations in response to oral glucose as well as higher fasting plasma triglyceride, cholesterol, and low-density lipoprotein cholesterol concentrations than did the control group (p < 0.005 to p < 0.001). In addition, high-density lipoprotein cholesterol concentrations were lower and the ratio of cholesterol to high-density lipoprotein cholesterol higher than control values in those with a pretransplant diagnosis of ischemic heart disease (p < 0.001). Values for almost all variables were intermediate in patients with a pretransplant diagnosis of idiopathic cardiomyopathy and in most instances were significantly different from both. Thus, male cardiac transplant recipients are dyslipidemic, relatively glucose intolerant, and hyperinsulinemic compared to normal volunteers. These changes, observed in patients with a pretransplant diagnosis of either ischemic heart disease or idiopathic cardiomyopathy, emphasize the important role of immunosuppression in the development of metabolic risk factors for CAD in these individuals.

Blood Glucose↗
PubMed1994

Effect of pravastatin treatment on glucose, insulin, and lipoprotein metabolism in patients with hypercholesterolemia.

Treatment of patients with type IIA hyperlipoproteinemia (HLP) with pravastatin for 3 months led to significant decreases (p < 0.001) in total cholesterol (7.18 +/- 0.30 to 5.75 +/- 0.30 mmol/L), LDL cholesterol (5.56 +/- 0.33 to 4.02 +/- 0.32 mmol/L), and ratio of total cholesterol to HDL cholesterol (6.5 +/- 0.4 to 4.6 +/- 0.4). Decreases of a similar magnitude were also seen in patients with type IIB HLP. Plasma glucose and insulin concentrations after an oral glucose load and from 8 AM to 4PM in response to meals were higher in patients with Type IIB HLP, who also had higher steady-state plasma glucose concentrations after an infusion of somatostatin, insulin, and glucose (12.4 +/- 1 vs 5.5 +/- 0.8 mmol/L, p < 0.001). Because steady-state plasma insulin concentrations were similar in both groups, patients with type IIB HLP were relatively insulin resistant. Furthermore, day-long plasma glucose concentrations and insulin resistance were modestly, but significantly (p < 0.01), greater after treatment in both groups. In conclusion, LDL cholesterol metabolism improved in hypercholesterolemic subjects treated with pravastatin, but the hypertriglyceridemia, insulin resistance, relative glucose intolerance, and hyperinsulinemia present in patients with type IIB HLP either did not improve with treatment or was somewhat worse.

Adult↗
PubMed1994

Recognition and processing of randomly fluctuating electric signals by Na,K-ATPase.

Previous work has shown that Na,K-ATPase of human erythrocytes can extract free energy from sinusoidal electric fields to pump cations up their respective concentration gradients. Because regularly oscillating waveform is not a feature of the transmembrane electric potential of cells, questions have been raised whether these observed effects are biologically relevant. Here we show that a random-telegraph fluctuating electric field (RTF) consisting of alternating square electric pulses with random lifetimes can also stimulate the Rb(+)-pumping mode of the Na,K-ATPase. The net RTF-stimulated, ouabain-sensitive Rb+ pumping was monitored with 86Rb+. The tracer-measured, Rb+ influx exhibited frequency and amplitude dependencies that peaked at the mean frequency of 1.0 kHz and amplitude of 20 V/cm. At 4 degrees C, the maximal pumping activity under these optimal conditions was 28 Rb+/RBC-hr, which is approximately 50% higher than that obtained with the sinusoidal electric field. These findings indicate that Na,K-ATPase can recognize an electric signal, either regularly oscillatory or randomly fluctuating, for energy coupling, with high fidelity. The use of RTF for activation also allowed a quantitative theoretical analysis of kinetics of a membrane transport model of any complexity according to the theory of electroconformational coupling (ECC) by the diagram methods. A four-state ECC model was shown to produce the amplitude and the frequency windows of the Rb(+)-pumping if the free energy of interaction of the transporter with the membrane potential was to include a nonlinear quadratic term. Kinetic constants for the ECC model have been derived. These results indicate that the ECC is a plausible mechanism for the recognition and processing of electric signals by proteins of the cell membrane.

Biophysical Phenomena↗
PubMed1994

Changes in glucose, insulin, lipid, lipoprotein, and apoprotein concentrations and insulin action in doxazosin-treated patients with hypertension. Comparison between nondiabetic individuals and patients with non-insulin-dependent diabetes mellitus.

Thirty patients with hypertension were enrolled in this study, 13 had non-insulin-dependent diabetes mellitus (NIDDM) and 17 were nondiabetic. Patients were treated with doxazosin for approximately 4 months, and blood pressure fell significantly (P < .001) in both nondiabetics (149/96 to 134/85 mm Hg) and in those with NIDDM (154/96 to 143/84 mm Hg). In the nondiabetic group, doxazosin treatment was associated with significant improvement in insulin-mediated glucose disposal (P < .05) and lower plasma insulin (P < .001), and triglyceride (P < .001) concentrations measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at noon). In addition, fasting total plasma (P < .001) and VLDL cholesterol (P < .01), and total plasma (P < .05), VLDL (P < .08), LDL (P < .01), HDL (P < .01) triglyceride concentrations were lower following doxazosin treatments in the nondiabetic group, as was the ratio of total to HDL cholesterol (P < .001). Finally, apoprotein B concentrations fell with doxazosin in the nondiabetic group (P < .01). Significant changes seen in the group with NIDDM included a decrease in the ratio of total to HDL cholesterol (P < .001) and a fall in apoprotein B concentration (P < .05). However, values for all other variables did not change significantly with treatment in this group. Thus, doxazosin treatment of nondiabetic subjects with high blood pressure was associated with a series of changes in glucose, insulin, and lipoprotein metabolism that should decrease risk of coronary heart disease (CHD) in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1994

Resistance to insulin-stimulated glucose uptake and dyslipidemia in Asian Indians.

Persons from the Indian subcontinent have elevated coronary heart disease risk. We measured insulin resistance with the insulin suppression test in 22 Asian Indian men and women and an equal number of control subjects of European ancestry matched for age and body mass index. Asian men and women had increased glucose and insulin responses to oral glucose tolerance tests (P < .05 by ANOVA) and had approximately 60% higher steady-state plasma glucose levels during the insulin suppression test (P < .001 by ANOVA), consistent with insulin resistance. In response to mixed meals, Asian women had higher plasma free fatty acids and glycerol concentrations than women of European ancestry (P < .02 by ANOVA), whereas Asian Indian men had similar free fatty acid and glycerol levels compared with men of European ancestry despite higher plasma insulin levels. Thus, results in both sexes were consistent with resistance to insulin suppression of free fatty acid levels in Asian Indians. Asian Indians of both sexes had higher fasting plasma triglyceride (P < .01) and lower high-density lipoprotein cholesterol (P < .01) concentrations than men and women of European ancestry. Resistance to insulin-stimulated glucose uptake and to insulin suppression of free fatty acid levels in Asian Indians is associated with a number of metabolic abnormalities that are demonstrated risk factors for coronary heart disease, including increased glucose, insulin, and triglyceride concentrations and decreased high-density lipoprotein cholesterol concentrations.

Asia↗