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Biomedical subjects

Y D Chen

Publications and source records attributed to Y D Chen.

At least 163 records · Page 9Linked to original sources
PubMed1987

Plasma lipid and lipoprotein concentrations in Chinese males with coronary artery disease, with and without hypertension.

Plasma lipid and lipoprotein concentrations were determined in 125 Chinese males with a medical history and electrocardiographic abnormalities consistent with the diagnosis of coronary artery disease (CAD). All subjects underwent coronary arteriography, and patients were divided into 3 groups based upon the results of the coronary arteriograms: 1) patients with a negative angiogram (CAD-, n = 30), without hypertension; 2) patients with a positive angiogram, without hypertension (CAD+, n = 70); and 3) patients with a positive angiogram, who had hypertension (CAD + HT, n = 25). Mean fasting plasma lipid and lipoprotein concentrations of these 3 groups of patients were compared to values in age and weight-matched groups of normal individuals (n = 80) and untreated patients with hypertension and no evidence of CAD (HT, n = 20). The results indicated that total plasma triglyceride, cholesterol, and LDL-cholesterol levels were significantly higher (P less than 0.001) than normal in patients with CAD+ and CAD + HT, whereas only plasma cholesterol levels were higher than normal in patients with HT. Although patients with CAD- had values intermediate between normal and CAD, the differences were not statistically significant. In addition, the ratio of LDL to HDL-cholesterol was significantly increased (P less than 0.05-0.001) above normal in patients with CAD+, CAD + HT, and HT. As before, the values in patients with CAD- were intermediate. These data document the presence of multiple abnormalities of lipid and lipoprotein concentration in patients with angiographic evidence of CAD, whether or not they were hypertensive. Furthermore, abnormalities in lipid and lipoprotein metabolism were seen in patients with hypertension alone.

Aged↗
PubMed1987

Relationships between plasma-free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and non-insulin-dependent diabetic individuals.

Measurements of fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations were made in 32 individuals--16 with normal glucose tolerance and 16 with non-insulin dependent diabetes mellitus (NIDDM)--further subdivided into two equal groups on the basis of body weight. In addition, endogenous glucose production was estimated in 32 subjects. Both fasting plasma glucose (251 +/- 14 v 86 +/- 1 mg/dL) and FFA (672 +/- 35 v 434 +/- 45 microEq/L) concentrations were significantly higher in patients with NIDDM (P less than .001), and the differences between normal and diabetic existed in both weight groups. Rates of endogenous glucose production were also significantly elevated (P less than .001) in diabetic (120 +/- 6 mg/m2 X min) as compared to normal subjects (73 +/- 6 mg/m2 X min), and these differences were also independent of degree of obesity. However, there were no significant differences between normal subjects and patients with NIDDM in either fasting or postprandial insulin concentrations. The similarity in insulin values for normal and diabetic subjects was true of both obesity groups, although insulin concentrations were somewhat higher in normal obese individuals as compared to their normal nonobese counterparts. Significant relationships were seen between values for fasting plasma glucose and endogenous glucose production (r = .89), fasting plasma glucose and fasting FFA (r = .64), and FFA levels and endogenous glucose production (r = .58) when all nonobese subjects were considered together. Essentially identical relationships, both qualitatively and quantitatively, were seen within the obese group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1987

Can free energy be transduced from electric noise?

Recently, it was shown that free energy can be transduced from a regularly oscillating electric field to do chemical or transport work when coupled through an enzyme with appropriate electrical characteristics. Here we report that randomly pulsed electric fields can also lead to work being done, giving rise to speculation as to whether appropriately designed enzymes can extract and convert free energy from the inherent fluctuations in their environment. The paradox is resolved by showing that equilibrium electrical noise resulting from the environment around an enzyme cannot be completely random but is correlated to the state that the enzyme is in. If the noise has the appropriate reciprocal interaction with the enzyme, its potential to serve as a free-energy source disappears. This is shown by Monte Carlo and other numerical calculations and is proven analytically by use of the diagram method. This method also is used to provide an explicit equation showing that, under a range of conditions, our model enzyme will be induced by uncorrelated ("autonomous") noise to undergo net cyclic flux. That work can be transduced from the "random" noise is demonstrated by using numerical methods.

Electrochemistry↗
PubMed1987

Theoretical studies on oscillations in microtubule polymerization.

Oscillations in the polymerization of microtubules have been studied theoretically, using differential equations and (more realistically) Monte Carlo simulations. There is gross qualitative agreement between theory and experiment but a really satisfactory model has not been found as yet.

Microtubules↗
PubMed1987

Asymmetry and external noise-induced free energy transduction.

The effect of fluctuations in rate constants on the kinetic behavior of cyclic reacting systems, caused by a fluctuating external parameter, is studied. It is shown (i) that the stochastic properties of the system can be analyzed analytically by using the usual master equation approach when the external parameter is fluctuating with discrete square pulses and (ii) that the system is equivalent to an expanded chemical kinetic system with no fluctuation in rate constants. When applied to a linear four-state cyclic enzyme system, the formalism can be used to prove analytically the finding that an enzyme can extract the free energy from an externally applied fluctuating membrane potential and perform active free energy transduction. The formalism also can be used to assess the asymmetry constraints imposed on the values of the rate constants in order for the model to work.

Biological Transport↗
PubMed1987

Age-related changes in postprandial plasma glucose, insulin, and free fatty acid concentrations in nondiabetic individuals.

Plasma glucose, insulin, and free fatty acid (FFA) concentrations were measured from 0800 to 1600 hours in 40 nondiabetic individuals, separated into younger (38 +/- 1.4 years) and older (64 +/- 1.5 years) age groups. Meals were served at 0800 (20% total daily calories) and 1200 h (40% of total daily calories), and blood drawn just before the 0800 hours meal and at hourly intervals thereafter until 1600 hours. Statistical evaluation of the results of these measurements indicated that day-long plasma glucose and insulin levels were higher in the older individuals. In contrast, the day-long FFA response was reduced in this age group. These data suggest that the ability of insulin to maintain normal plasma glucose levels deteriorates with age, whereas regulation of FFA levels does not.

Adult↗
PubMed1987

Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus.

Plasma glucose, insulin, FFA, glucagon, and GH concentrations were measured over an 8-h period in normal subjects and patients with noninsulin-dependent diabetes mellitus (NIDDM). Meals were consumed at 0800 h (20% of daily calories) and noon (40% of daily calories), and measurements were made hourly from 0800-1600 h. Day-long plasma glucose, insulin, and FFA concentrations were higher than normal (by two-way analysis of variance) in patients with NIDDM, whether obese or nonobese. In addition, day-long plasma glucagon concentrations were also higher than normal (by two-way analysis of variance) in both nonobese and obese patients with NIDDM. Furthermore, direct relationships were found between the total plasma glucagon response from 0800-1600 h and total plasma glucose (r = 0.57; P less than 0.001) and FFA (r = 0.30; P less than 0.06) responses. In contrast, plasma GH levels were not increased in patients with NIDDM. These data demonstrate that ambient plasma concentrations of both glucose and FFA are higher in patients with NIDDM, despite the fact that coexisting plasma insulin levels are equal to or higher than normal. The higher day-long plasma glucagon levels in patients with NIDDM may contribute to their higher plasma glucose and FFA concentrations.

Activity Cycles↗
PubMed1987

Resistance to insulin suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in noninsulin-dependent diabetes mellitus.

The ability of insulin to stimulate tissue glucose uptake and lower plasma FFA concentrations was quantified in 12 individuals with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM), further subdivided into obese and nonobese subjects. Measurements were made during 5-h glucose clamp studies, carried out at plasma insulin concentrations of about 10 microU/ml (0-150 min) and about 60 microU/ml (150-300 min). Differences between the patient groups were compared by two-way analysis of variance. The ability of insulin to either suppress plasma FFA concentrations or stimulate glucose uptake was significantly reduced (P less than 0.001) in patients with NIDDM, and this was true of both the obese and nonobese groups. The defect in the ability of insulin to suppress plasma FFA concentrations in patients with NIDDM was more apparent at the lower insulin concentration, whereas resistance to insulin-stimulated glucose uptake in NIDDM was more dramatic at the high insulin concentration. Finally, a significant correlation (r = -0.67; P less than 0.001) between insulin-stimulated glucose uptake and plasma FFA concentration was found in the entire group. These data emphasize the fact that patients with NIDDM are resistant to multiple actions of insulin, and that the magnitudes of the defect in insulin suppression of plasma FFA levels and stimulation of tissue glucose uptake are roughly comparable.

Aged↗
PubMed1987

Can insulin resistance exist as a primary defect in noninsulin-dependent diabetes mellitus?

In this study we have attempted to quantify the plasma insulin response to glucose and insulin action in 22 nonobese subjects: 11 with normal glucose tolerance and 11 with mild [mean fasting plasma glucose concentration, 128 +/- (+/- SEM) 5 mg/dL] noninsulin-dependent diabetes mellitus (NIDDM). Estimates of the plasma insulin response were made by determining the plasma insulin concentration at hourly intervals from 0800-1600 h, before and after mixed meals consumed at 0800 h (breakfast) and 1200 h (lunch). Insulin action was assessed by measuring glucose uptake during insulin clamp studies performed at steady state plasma insulin levels of approximately 10 and 60 microU/mL, with the difference between the 2 values defined as insulin-stimulated glucose uptake. Plasma glucose (P less than 0.001) and insulin (P less than 0.001) concentrations were significantly higher in patients with NIDDM throughout the 8-h period (by two-way analysis of variance). However, mean (+/- SEM) insulin-stimulated glucose uptake was markedly reduced (P less than 0.001) in patients with type 2 diabetes mellitus (112 +/- 72 vs. 336 +/- 44 mg/m2 min-1). Thus, patients with NIDDM and mild fasting hyperglycemia were both insulin resistant and hyperinsulinemic compared to normal individuals. These data indicate that a defect in insulin-stimulated glucose uptake can occur in NIDDM in the absence of significant hyperglycemia and/or hypoinsulinemia.

Aged↗
PubMed1987

High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL.

High density lipoprotein (HDL) kinetics were studied by injecting [3H]apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster [0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001] and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients.

Aged↗
PubMed1987

Abnormalities of carbohydrate and lipid metabolism in patients with hypertension.

Plasma glucose, insulin, and lipoprotein concentrations were determined in 20 men with hypertension, and compared with values in 20 normotensive men of comparable age and body mass index. The results demonstrated a significant increase in both the plasma glucose and insulin response to a 75-g oral glucose challenge (two-way analysis of variance). In addition, a significant correlation existed between the plasma blood pressure. Finally, the greater the plasma glucose insulin response to oral glucose and both systolic and diastolic and insulin responses to oral glucose, the lower the plasma high-density lipoprotein concentrations, and the higher the ratio of plasma low-density lipoprotein cholesterol to high-density lipoprotein cholesterol. Thus, abnormalities of plasma glucose, insulin, and lipoprotein metabolism exist in patients with untreated hypertension, and these changes may contribute to the increased risk for coronary artery disease associated with hypertension.

Blood Glucose↗
PubMed1987

Role of insulin in regulation of high density lipoprotein metabolism.

The effect of alloxan-induced insulin deficiency on high density lipoprotein (HDL) metabolism was studied in rabbits. Rabbits with alloxan-induced diabetes had significantly higher (P less than 0.001, mean +/- SEM) plasma concentrations of glucose (541 +/- 13 vs. 130 +/- 2 mg/dl), triglyceride (2851 +/- 332 vs. 101 +/- 10 mg/dl), and total plasma cholesterol (228 +/- 55 vs. 42 +/- 4 mg/dl) than did normal control rabbits. However, diabetic rabbits had lower plasma HDL-cholesterol (7.2 +/- 1 vs. 51.3 +/- 1.3 mg/dl, P less than 0.001) and HDL apoA-I (38.3 +/- 6.0 vs. 87.2 +/- 4.3 mg/dl, P less than 0.001) concentrations. HDL kinetics were compared in diabetic and normal rabbits, using either 125I-labeled HDL or HDL labeled with 125I-labeled apoA-I, and it was demonstrated that HDL fractional catabolic rate (FCR) was slower and residence time was longer in the diabetic rabbits when either tracer was used. The slow FCR and the low apoA-I pool size led to reduced apoA-I/HDL synthetic rate in diabetic rabbits (0.97 +/- 0.11 vs. 0.34 +/- 0.07 mg per kg per hr). Thus, the reduced plasma HDL-cholesterol concentrations seen in rabbits with alloxan-induced insulin deficiency was associated with a lower total apoA-I/HDL synthetic rate. Since insulin treatment restored to normal all of the changes in plasma lipoprotein concentration and kinetics seen in diabetic rabbits, it is unlikely that the phenomena observed were secondary to a nonspecific toxic effect of alloxan. These data strongly support the view that insulin plays an important role in regulation of HDL metabolism.

Animals↗
PubMed1986

A theoretical study of double-inhibitor-titration curves in free-energy-transducing networks.

The general relationship between the double-inhibitor-titration curves and the kinetic properties of pumps in a delocalized chemiosmotic free-energy-transducing network is studied. The kinetic conditions for a delocalized system to generate the observed double-inhibitor-titration results are derived and the effectiveness of double-inhibitor experiments in discriminating between the localized and the delocalized proton-coupling mechanisms is assessed. It is found that, using simple enzymatic cycles for the kinetics of the pumps in a delocalized network, one can reproduce the experimentally measured double-inhibitor-titration curves that were widely used to argue against the delocalized mechanism. This implies that double-inhibitor-titration curves alone are not sufficient to discriminate between localized and delocalized coupling systems. Additional information concerning the kinetic responses of isolated pumps on the proton gradient across the membrane and inhibitor concentrations are required.

Adenosine Diphosphate↗
PubMed1986

The effect of colchicine on cholesterol processing by the progesterone-producing cells of the luteinized ovary.

Previously, we indicated that luteal cells from colchicine-treated superovulatory (luteinized) rats show decreased capacity for progesterone production. The current study investigates the possibility that colchicine exerts this effect by interfering with the mechanism by which cholesterol is processed and/or synthesized by luteal cells. To this end, animals were treated with saline or colchicine after which the luteinized ovary or isolated luteal cells were assayed for their cholesterol content, their ability to synthesize cholesterol endogenously, or their ability to utilize lipoprotein-delivered cholesterol for the production of progesterone. The results show that animals treated with colchicine show a number of changes in luteal cell cholesterol metabolism: namely a 60% decline in stored cholesterol, a 3-fold rise in the activity of the cholesterol synthesizing enzyme HMG CoA reductase (although no change occurs in other cholesterol metabolizing enzymes), and a 3-fold rise in the capacity of the cells to incorporate precursor [14C]acetate into cholesterol. On the other hand, cells of animals treated with colchicine or cells treated with colchicine under in vitro circumstances are unable to fully utilize cholesterol provided by high density lipoproteins (HDL): this occurs despite the fact that the binding of HDL particles to luteal cells is quite normal after colchicine treatment. These findings are consistent with the view that a primary effect of colchicine on luteal cell progesterone production is in preventing the normal uptake of HDL-cholesterol.

Animals↗
PubMed1986

Is the insulin resistance of patients with noninsulin-dependent diabetes mellitus secondary to insulin deficiency?

Defects in both insulin secretion and action have been documented in patients with noninsulin-dependent diabetes mellitus (NIDDM), leading to the suggestion that both fasting hyperglycemia and insulin resistance in NIDDM are secondary to insulin deficiency. In order to test this hypothesis, insulin secretion (plasma insulin response to oral glucose) and insulin action (insulin clamp) were determined in 25 patients with NIDDM. The results documented relationships between incremental plasma insulin response to glucose and degree of fasting hyperglycemia (r = -.045, P less than 0.05) and insulin-stimulated glucose utilization (r = 0.25, P = NS). These data indicate that differences in insulin secretory response accounted for only approximately 20% of the variance in fasting plasma glucose level and 6% of the variance in insulin resistance in NIDDM. Thus, differences in insulin-secretory response contribute modestly to magnitude of glycemia, and not at all to variations in insulin resistance in NIDDM, permitting rejection of the hypothesis that insulin resistance is secondary to insulin deficiency.

Age Factors↗
PubMed1986

How enzymes can capture and transmit free energy from an oscillating electric field.

Recently, it has been demonstrated that free energy from an alternating electric field can drive the active transport of Rb+ by way of the Na+, K+-ATPase. In the present work, it is shown why many transmembrane enzymes can be expected to absorb free energy from an oscillating electric field and transduce that to chemical or transport work. In the theoretical analysis it turned out to be sufficient that (i) the catalytic process be accompanied by either net or cyclic charge translocation across the membrane and (ii) the stability of the enzyme states involved be asymmetric. Calculations based on a four-state model reveal that free-energy transduction occurs with sinusoidal, square-wave, and positive-only oscillating electric fields and for cases that exhibit either linear or exponential field-dependent rate constants. The results suggest that in addition to oscillating electric field-driven transport, the proposed mechanism can also be used to explain, in part, the "missing" free energy term in the cases in which ATP synthesis has been observed with insufficient transmembrane proton electrochemical potential difference.

Adenosine Triphosphatases↗