Biomedical subjects

Y D Chen

Publications and source records attributed to Y D Chen.

At least 127 records · Page 7Linked to original sources

PubMed1990

The diagram methods for the evaluation of exchange fluxes in membrane transport systems.

In this paper theoretical methods for the evaluation of fluxes of ligand exchange processes in a transporter-mediated membrane transport system are studied. The exchange process of a transport system is defined as a set of reactions of the transporters in the membrane that do not result in a complete turnover and must include the following consecutive sequence of steps: the binding of ligands from bath 1 and a subsequent release of bound ligands to bath 2 followed immediately by a binding of ligands from bath 2 and a subsequent release of bound ligands to bath 1. Thus, unlike the ordinary one-way cycles, the completion of an exchange process does not result in a net transport of ligands across the membrane. However, since it exchanges the ligands between the two baths, the exchange process of a transport system is closely related to the operational tracer flux of labelled ligands in the system. In this paper, both the numerical and the analytical procedures for the evaluation of exchange fluxes in any given biochemical diagram are discussed. In particular, we show that the exchange fluxes of a given kinetic diagram, like one-way cycle fluxes, can be expressed analytically in terms of the rate constants of the diagram with the use of either the original diagram or an expanded diagram. The diagram methods presented in this paper should be very useful in analyzing the mechanisms of transporter-mediated transport systems when tracer flux data are available.

Biological Transport↗

PubMed1990

Diffusion and redistribution of lipid-like molecules between membranes in virus-cell and cell-cell fusion systems.

The kinetics of redistribution of lipid-like molecules between the membranes of two fused spherical vesicles is studied by solving the time-dependent diffusion equation of the system. The effects on the probe redistribution rate of pore size at the fusion junction and the relative sizes of the vesicles are examined. It is found that the redistribution rate constant decreases significantly, but not drastically, as the relative size of the pore to that of the vesicles decreases (the bottleneck effect). In general, the time scale of the probe redistribution rate is determined by the size of the vesicles that is loaded with the probe before the activation of the fusion. For a pore size 50 A in diameter and a typical diffusion coefficient of 10(-8) cm2/s for lipids, the mixing half times for typical virus-cell and cell-cell fusion systems are less than 30 ms and above 200 s, respectively. Thus, although the redistribution of lipid-like probes by diffusion is not rate limiting in virus-cell fusion, redistribution by diffusion is close to rate limiting in spike-protein mediated cell-cell fusion.

Biophysical Phenomena↗

PubMed1990

Effect of chronic renal failure on high-density lipoprotein kinetics.

Plasma lipid and lipoprotein concentration and high density lipoprotein (HDL) kinetics were determined in control subjects and patients with chronic renal failure (CRF). Results demonstrated that plasma triglyceride (TG) concentration was significantly higher (P less than 0.001) in patients with CRF, associated with a significant increase in plasma VLDL-cholesterol (P less than 0.002) and a significant decrease (P less than 0.05) in plasma HDL-cholesterol concentration. The rate of removal of 125I-apoAI/HDL from plasma was slower (P less than 0.001) in the patients with CRF, resulting in an increase in the residence time of 125I-apoAI/HDL (P less than 0.001) and a decrease in the fractional catabolic rate (P less than 0.001). Since plasma apoAI concentration was lower in patients with CRF, total apoAI/HDL synthetic rate was also significantly (P less than 0.05) decreased. These data provide support for the view that low plasma HDL-cholesterol concentrations in patients with CRF are related to decreases in the synthetic rate of apoAI/HDL.

Adult↗

PubMed1990

Comparison of the effects of differences in ratio of waist to hip girth and body mass index on carbohydrate metabolism in Chinese females.

Plasma glucose and insulin concentration and the ability of physiological hyperinsulinemia to dispose of a glucose load were determined in 26 healthy, nondiabetic, Chinese females. The study population was divided in half on the basis of two indices of obesity: 1) body mass index (greater than or less than 25.3 kg/m2) and 2) ratio of waist to hip girth (greater than or less than 0.83). When these groups were compared on the basis of the three measured variables, the results indicated that the untoward metabolic effects of obesity were, if anything, more prominent when subjects were divided on the basis of body mass index as compared to a division based on the ratio of waist to hip girth. Similarly, correlation coefficients between body mass index and plasma glucose response, plasma insulin response, and insulin-stimulated glucose disposal were equal to or greater than the correlation coefficients between ratio of waist to hip girth and the same three variables. These data suggest that the impact of differences in abdominal obesity, as reflected in measurement of the ratio of waist to hip girth, is no greater than the effect of overall obesity, as estimated by calculation of body mass index, on plasma glucose and insulin responses to oral glucose and insulin-stimulated glucose disposal in Chinese females who are not massively obese.

Abdomen↗

PubMed1990

Effect of prazosin treatment on HDL kinetics in patients with hypertension.

The effect of prazosin treatment on blood pressure, plasma HDL-cholesterol concentration, and apoprotein-AI/HDL (apoAI/HDL) kinetics was studied in 11 patients with mild hypertension. Blood pressure (mean +/- SEM) fell from 143 +/- 1/96 +/- 1 to 134 +/- 1/86 +/- 1 mm Hg after 4 to 5 months of prazosin treatment (P less than .001), associated with an increase in plasma HDL-cholesterol concentration from 38 +/- 2 to 46 +/- 2 mg/dL (P less than .001). Both the fractional catabolic rate (FCR) and total synthetic rate of apoAI/HDL, which were higher than previous reported values for normal individuals, decreased from 0.36 +/- 0.02 to 0.30 +/- 0.02 L/day and 17.4 +/- 1.1 to 13.8 +/- 1.1 mg/kg/min, respectively. These changes were statistically significant, and the post-treatment values for both variables were now within the normal range. When the decay curve was further analyzed by nonlinear curve fitting, it was shown that the return to normal of the FCR of apoAI/HDL in patients treated with prazosin was accounted for by the decrease of the decay constants of the second [p(2)] and third [p(3)] components of the 125I-AI/HDL disappearance curve. In conclusion, abnormalities in HDL concentration and HDL kinetics exist in patients with very mild hypertension. These defects were significantly improved with prazosin treatment, and this may render the compound of particular clinical benefit in the treatment of patients with mild hypertension.

Apolipoprotein A-I↗

PubMed1990

Metabolic effects of diuretic and beta-blocker treatment of hypertension in patients with non-insulin-dependent diabetes mellitus.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension were studied before and after three months of combined beta-blocker-diuretic treatment. Blood pressure fell significantly (P less than .001) from (mean +/- SEM) 167 +/- 3/99 +/- 1 to 142 +/- 3/88 +/- 1 mm Hg. However, mean (+/- SEM) fasting plasma glucose concentration increased significantly (P less than .001) from 132 +/- 11 to 153 +/- 10 mg/dL. In addition, significant increases (P less than .05) were noted in fasting concentration of plasma total triglyceride, very-low-density lipoprotein (VLDL)-triglyceride and VLDL-cholesterol, whereas fasting plasma high-density lipoprotein (HDL)-cholesterol was significantly lower (P less than .05). Thus, a common treatment program for hypertension exacerbated the abnormalities of carbohydrate and lipid metabolism commonly present in patients with NIDDM. Since the changes noted would increase risk of vascular disease, attention should be focused on selection of treatment programs for lowering blood pressure in patients with NIDDM in order to avoid this outcome.

Adrenergic beta-Antagonists↗

PubMed1990

Effect of low fat-high carbohydrate diets in hypertensive patients with non-insulin-dependent diabetes mellitus.

Effects of variations in dietary fat and carbohydrate content on various aspects of glucose, insulin, and lipoprotein metabolism were evaluated in 11 patients with hypertension, who also had non-insulin-dependent diabetes mellitus (NIDDM). All of these patients were being treated with sulfonylureas, thiazides, and beta-adrenergic receptor antagonists. The comparison diets contained either 40 or 60% of total calories as carbohydrate, with reciprocal changes in fat content from 40 to 20%. The diets were consumed in a random order for 15 days in a crossover experimental design. The ratio of polyunsaturated to saturated fat and total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P less than .001) elevated throughout the day when patients consumed the 60% carbohydrate diet. Fasting plasma total and very-low-density lipoprotein (VLDL) and triglyceride (TG) concentrations increased by 30% (P less than .001) after 15 days on the 60% carbohydrate diet. Total plasma cholesterol concentrations were similar on both diets, as were low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations.

Analysis of Variance↗

PubMed1990

Coronary artery disease in Chinese males without hypercholesterolaemia.

The aim of this study was to determine the frequency of various metabolic risk factors for coronary artery disease (CAD) in 246 male patients studied over a 2-year period. CAD was diagnosed on the basis of a history indicative of angina pectoris, an electrocardiogram diagnostic of myocardial ischaemia, and a positive coronary angiogram. Thirty-eight per cent of this population had diabetes, hypertension or both. Of the remaining individuals, 39% had a plasma cholesterol concentration greater than 5.2 mmol l-1, whereas 23% had a cholesterol concentration less than 5.2 mmol l-1. Plasma lipid and lipoprotein levels of a non-smoking subset of those subjects with a total cholesterol concentration less than 5.2 mmol l-1 were compared with values of a matched group of individuals who did not have significant vessel disease as revealed by angiography. The results of these investigations indicated that patients with CAD and a plasma cholesterol concentration less than 5.2 mmol l-1 exhibited an increase in plasma triglyceride concentration and a decrease in plasma HDL-cholesterol concentration. Since these subjects were not diabetic, hypertensive or hypercholesterolaemic, it is suggested that the observed changes in triglyceride and HDL metabolism made a major contribution to the CAD in these individuals.

Aged↗

PubMed1990

Insulin insensitivity in offspring of parents with type 2 diabetes mellitus.

Measurements were made of the plasma glucose and insulin responses to a 75 g oral glucose challenge in 50 Chinese born in Taiwan, divided into two groups on the basis of family history of Type 2 diabetes. Twenty-five individuals (age 29 +/- 5 (+/- SD) years) had 2 parents with normal oral glucose tolerance, whereas at least 1 parent had Type 2 diabetes in the other 25 subjects (age 30 +/- 6 years). In addition, in vivo insulin action was estimated by determining the steady-state plasma glucose concentration during a 3-h continuous infusion of glucose, insulin, and somatostatin. Steady-state plasma glucose concentration was used as a measure of insulin-induced glucose disposal. The 50 subjects were non-obese, and of comparable gender distribution and body mass index. Plasma glucose and insulin concentrations in response to oral glucose were similar in the two groups. However, the steady-state plasma glucose concentration was significantly (p less than 0.01) higher in offspring with a family history of Type 2 diabetes when compared by two-way analysis of variance (mean +/- SE was 5.87 +/- 0.27 vs 5.12 +/- 0.32 mmol l-1). This difference was found despite a significantly (p less than 0.01) higher steady-state plasma insulin concentration during the infusion studies (0.705 +/- 0.027 vs 0.643 +/- 0.025 nmol l-1) in offspring of people with diabetes. The results support the view that resistance to insulin-stimulated glucose uptake is present in offspring of diabetic parents.

Adult↗

PubMed1990

Acute changes in plasma non-esterified fatty acid concentration do not change hepatic glucose production in people with type 2 diabetes.

The effect of changes in plasma non-esterified fatty acid concentration (NEFA) on plasma glucose concentration, hepatic glucose production (Ra), and glucose disposal (Rd) rates was determined in 14 patients with Type 2 diabetes. Seven patients had relatively mild fasting hyperglycaemia (less than 10.0 mmol l-1), whereas the remaining seven had relatively severe fasting hyperglycaemia (greater than 14.0 mmol l-1). Each patient was infused from 2000 to 0800 h with 3-3H-glucose on two occasions, with or without neutral fat emulsion and heparin (mild hyperglycaemia group), or with or without nicotinic acid (severe hyperglycaemia group). Plasma NEFA concentration increased from 0.33 +/- 0.06 (+/- SE) to 4.78 +/- 0.42 mmol l-1 in response to the lipid and heparin infusion, but plasma glucose concentration (7.8 +/- 0.7 vs 7.4 +/- 0.8 mmol l-1), Ra (0.44 +/- 0.02 vs 0.46 +/- 0.02 mmol m-2 min-1), and Rd (0.42 +/- 0.02 vs 0.46 +/- 0.02 mmol m-2 min-1) were unchanged. Nicotinic acid decreased plasma NEFA concentration from 0.54 +/- 0.15 to 0.23 +/- 0.08 mmol l-1, but plasma glucose (15.0 +/- 1.0 vs 15.5 +/- 1.4 mmol l-1), Ra (0.74 +/- 0.07 vs 0.68 +/- 0.07 mmol m-2 min-1), and Rd (0.73 +/- 0.07 vs 0.68 +/- 0.07 mmol m-2 min-1) were unchanged. The results indicate that acute changes in plasma NEFA concentration did not lead to any change in overnight glucose production or disposal rates.

Blood Glucose↗

PubMed1990

Does glucagon increase plasma free fatty acid concentration in humans with normal glucose tolerance?

To evaluate the effect of glucagon on regulation of plasma FFA concentration, continuous iv infusions of either somatostatin (S) or somatostatin (S) plus glucagon (G) were administered to 18 individuals with normal glucose tolerance. In 9 of these individuals there was no insulin replacement, whereas in the other 9 individuals enough insulin was infused to restore the insulin concentration to the basal level. Measurements were made of plasma glucose, insulin, G, and FFA concentrations as well as hepatic glucose production (Ra). The results indicated that plasma FFA concentrations were significantly lower when G was infused (S greater than S + G) regardless of whether insulin was infused. However, similar elevations of the plasma G concentration did lead to higher values of Ra and plasma glucose, although the basal concentration of plasma insulin decreased the increases in Ra and plasma glucose caused by G. The ability of a similar amount of insulin to lower plasma FFA concentrations was greater in magnitude than the decrease in Ra. These data indicate that G does not increase plasma FFA concentrations in normal individual, and that insulin plays a role of greater magnitude in suppression of plasma FFA concentrations than in inhibition of Ra.

Blood Glucose↗

PubMed1990

Effect of difference in glucose infusion rate on quantification of hepatic glucose production.

This study was carried out to determine whether hepatic glucose production (HGP) could be suppressed in normal subjects by infusing different amounts of glucose, in the absence of significant changes in steady state plasma glucose (SSPG) or insulin (SSPI) concentrations. Consequently, subjects were infused with somatostatin (215 nmol/h), insulin (28.7 pmol/m2.min), and amounts of glucose varying from 0-200 mumol/m2.min in the absence or presence of glucagon (5.2 pmol/m2.min). SSPI concentrations were constant (60-70 pmol/L) during these studies, and values for the total glucose appearance rate (glucose infusion rate plus HGP) and SSPG did not vary significantly as a function of the rate of exogenous glucose infusion. However, values for HGP fell in response to increases in glucose infusion rate and could be suppressed to approximately 50% of the original value despite the fact that SSPG, SSPI, and glucose appearance rate did not change significantly. These data indicate that HGP can be regulated by varying the rate of exogenous glucose infusion during glucose clamp studies.

Adult↗

PubMed1990

Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance.

It has been proposed that central obesity, by virtue of the enhanced lipolytic activity of abdominal adipose tissue, leads to higher plasma FFA concentrations, which, in turn, decrease both hepatic removal of insulin and insulin-stimulated glucose uptake by peripheral tissues. In short, the predicted consequences of abdominal obesity are elevations in circulating FFA and insulin levels as well as insulin resistance. The goal of this study was to evaluate the relationships predicted by the overall hypothesis; this study was carried out in 31 obese females, defined as having normal glucose tolerance (n = 12), impaired glucose tolerance (n = 8), or noninsulin-dependent diabetes mellitus (n = 11). Abdominal obesity was estimated by determining the ratio of waist to hip girth, fasting and postprandial plasma FFA and insulin concentrations were measured at hourly intervals from 0800-1600 h, and insulin-stimulated glucose disposal was quantified by the euglycemic hyperinsulinemic clamp technique. The first step in the postulated sequence of events to be tested was that the greater the WHR, the higher the total integrated plasma FFA response. The correlation coefficient between these two variables was 0.29, indicating that the results did not support the prediction. Furthermore, we could not demonstrate any relationship between the magnitude of the plasma FFA and insulin responses (r = 0.20; P = NS). However, there was a modest inverse relationship between height of circulating plasma insulin concentration and a decrease in insulin-stimulated glucose uptake (r = -0.43; P less than 0.03) in the group as a whole. On the other hand, when the three groups were analyzed individually, a significant inverse relationship was only seen in the control group (r = -0.67), and a direct relationship was actually seen in patients with impaired glucose tolerance (r = 0.88). Furthermore, when the mean responses for the variables in each of the three groups were compared, it was apparent that the postulated relationships between abdominal obesity, plasma FFA concentration, and insulin secretion and action were not present. Thus, the data presented do not support the hypothesis that differences in the degree of central obesity play an important role in regulation of plasma concentrations of either FFA or insulin or in modulation of insulin-stimulated glucose uptake in the patients we studied.

Adipose Tissue↗

PubMed1990

Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients.

The effect of metformin treatment on various aspects of carbohydrate and lipoprotein metabolism has been defined in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were studied before and after approximately 4 mo of metformin therapy. Treatment was initiated with a single dose of 500 mg/day, increased at weekly intervals, and maintained at a final dose of 2.5 g/day (given at divided intervals) for the last 3 mo of the treatment program. Results demonstrated that both fasting and postprandial glucose concentrations were significantly lower after metformin administration, with the greatest change seen after meals. As a result, the total incremental plasma glucose response above basal measured from 0800 to 1600 after metformin was less than 25% of that seen initially. The improvement in ambient plasma glucose concentration in association with metformin occurred despite a modest but statistically significant decrease in circulating plasma insulin concentration. In addition, insulin-stimulated glucose uptake measured during hyperinsulinemic clamp studies was similar before and after metformin treatment. Furthermore, changes in insulin binding and insulin internalization by isolated monocytes did not correlate with the improvement in glycemic control. Thus, the ability of metformin to lower plasma glucose concentration in NIDDM does not appear to be secondary to an improvement in insulin action. Finally, metformin treatment was associated with a significant (P less than 0.01) decrease in plasma triglyceride concentration and an increase in plasma high-density lipoprotein cholesterol concentration. These results indicate that metformin treatment of patients with NIDDM led to an improvement in both glycemic control and lipoprotein metabolism.

Blood Glucose↗

PubMed1989

Effect of prazosin treatment on carbohydrate and lipoprotein metabolism in patients with hypertension.

This study evaluated the effect of prazosin in controlled mild hypertension and evaluated select metabolic changes that occurred with prazosin monotherapy. Various aspects of glucose, insulin, and lipid metabolism were studied before and after approximately 10 weeks of prazosin treatment in 12 patients with mild hypertension. Prazosin was well tolerated and induced a significant decrease (p less than 0.001) in both systolic and diastolic blood pressures, without any change in body weight. Plasma concentrations of glucose, free fatty acid, and lactate, which were measured hourly from 8 A.M. to 4 P.M. following meals consumed at 8 A.M. and noon, did not change with prazosin treatment. However, the plasma insulin response from 8 A.M. to 4 P.M. decreased significantly (p less than 0.001) following prazosin treatment. In addition, fasting plasma triglyceride and cholesterol concentrations were significantly lower (p less than 0.05) in prazosin-treated persons, as were postprandial triglyceride concentrations (p less than 0.001). Lower total plasma triglyceride and cholesterol concentrations were accounted for by decreases in very low-density lipoprotein cholesterol and triglyceride and low-density lipoprotein cholesterol and triglyceride, whereas both high-density lipoprotein triglyceride and high-density lipoprotein cholesterol concentrations increased following prazosin treatment. Finally, although both apolipoprotein A1 and apolipoprotein B concentrations decreased in association with prazosin treatment, the decrease in apolipoprotein B was much greater in magnitude, leading to an increase in the ratio of apolipoprotein A1 to apolipoprotein B. In this study, treatment of mild hypertension with prazosin led to lower blood pressures and changes in insulin and lipoprotein metabolism that are important in this patient population.

Adult↗

PubMed1989

Relationship between glucose tolerance, insulin secretion, and insulin action in non-obese individuals with varying degrees of glucose tolerance.

Plasma glucose and insulin concentration following a 75 g oral glucose challenge and glucose uptake during a hyperinsulinaemic glucose clamp study were determined in 50 non-obese individuals. The study population was divided into five groups on the basis of their glucose tolerance: normal, impaired glucose tolerance, Type 2 (non-insulin-dependent) diabetes mellitus with fasting plasma glucose of less than 8 mmol/l, between 8-15 mmol/l, and more than 15 mmol/l. The plasma insulin response was significantly greater (p less than 0.001) than normal in those with either impaired glucose tolerance or Type 2 diabetes and a fasting plasma glucose concentration less than 8 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1989

On the use of self-quenching fluorophores in the study of membrane fusion kinetics. The effect of slow probe redistribution.

In glycoprotein-mediated pH-induced fusion of virus to animal cells, the mixing of materials between membranes or between cytoplasmic spaces occurs after the virus-cell complex has gone through a number of activation reactions. The monitoring of the fluorescence changes measured in a fusing system using self-quenching probes could reflect not only the kinetics of activation, but also the redistribution reaction of probes. For instance, time delay seen in the onset of fluorescence changes after triggering the fusion reaction (S.J. Morris, D.P. Sarkar, J.M. White and R. Blumenthal, J. Biol. Chem. (1989) 3972), could be due to rate-limiting probe redistribution kinetics. In this paper we examined in detail the effect of probe redistribution rates on fusion kinetics. Simulations were performed using a very simple model with two fusion-activation steps and an exponential probe redistribution kinetics. We conclude that if the rates of probe redistribution are faster than or equal to those of viral glycoprotein activation, the kinetics of the fusion reaction are not significantly affected.

Animals↗

PubMed1989

The combined use of insulin and sulfonylurea therapy in patients with non-insulin dependent diabetes mellitus.

This study was initiated in order to evaluate the clinical efficacy of glipizide treatment in 18 patients with non-insulin dependent diabetes mellitus in poor glycemic control with insulin. Insulin dose was kept constant, and various facets of carbohydrate and lipid metabolism were evaluated before and from 4-6 months after the addition of glipizide. The results indicated that fasting and post-prandial glucose concentration were significantly (P less than 0.001) reduced following glipizide treatment, associated with a commensurate fall in glycosylated hemoglobin concentration. The average fall in fasting plasma glucose concentration in the total patient group approximated 60 mg/dl, and the mean decrement in 8 of the 18 patients who had a fall of more than 70 mg/dl in fasting glucose was 93 mg/dl. These results demonstrate that the addition of glipizide to the treatment program of patients with non-insulin dependent diabetes mellitus poorly controlled on insulin can lead to substantial clinical benefit.

Adult↗