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Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 955 records · Page 53Linked to original sources
PubMed1994

Simulation and animation of sensor-driven robots.

Most simulation and animation systems utilized in robotics are concerned with simulation of the robot and its environment without simulation of sensors. These systems have difficulty in handling robots that utilize sensory feedback in their operation. In this paper, a new design of an environment for simulation, animation, and visualization of sensor-driven robots is presented. As sensor technology advances, increasing numbers of robots are equipped with various types of sophisticated sensors. The main goal of creating the visualization environment is to aid the automatic robot programming and off-line programming capabilities of sensor-driven robots. The software system will help the users visualize the motion and reaction of the sensor-driven robot under their control program. Therefore, the efficiency of the software development is increased, the reliability of the software and the operation safety of the robot are ensured, and the cost of new software development is reduced. Conventional computer-graphics-based robot simulation and animation software packages lack of capabilities for robot sensing simulation. This paper describes a system designed to overcome this deficiency.

Artificial Intelligence↗
PubMed1994

Effects in vitro of new growth hormone releasing peptide (GHRP-1) on growth hormone secretion from ovine pituitary cells in primary culture.

Continuous perifusion of pituitary cells was used to study the effects of a newly synthesized GHRP (GHRP-1 or KP 101) on growth hormone (GH) secretion from ovine pituitary cells and these have been compared to effects of growth hormone-releasing factor (GRF) and the original growth hormone-releasing peptide (GHRP-6). GH was continuously released at a constant rate during perifusion and secretion was increased by KP 101, GHRP-6 and GRF in a dose-dependent manner. The half-maximal effective dose of KP 101 and GHRP-6 was 10(-7) M, an order of magnitude higher than that for GRF. The maximal effects of KP 101 and GHRP-6 were similar but significantly less than the maximal effect of GRF. Blockade of calcium channels with Cd2+ (2 mM) totally and reversibly abolished the releasing effects of all three peptides. Like GHRP-6, the GH release induced by KP 101 was not affected by a GRF antagonist ([Ac-Tyr1, D-Arg2]-GRF 1-29, 1 microM) which significantly reduced the effect of GRF on GH release. For each peptide, the response to a second application (1 h after the first application) was lower than the first response. When GRF (or KP 101, GHRP-6) was applied first and then KP 101 or GHRP-6 (or GRF) given 1 h later, the second response was not attenuated. Only a small additive effect on the release of GH by GRF was obtained by the co-administration of either KP 101 or GHRP-6. This result was achieved with maximal doses of the peptides, but not with half-maximal doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Clonal analysis of Porphyromonas gingivalis by the arbitrarily primed polymerase chain reaction.

Genetic analysis of Porphyromonas gingivalis strains may distinguish between virulent and nonvirulent strains and also may be used to trace individual strains in epidemiological studies. The present study examined the utility of the arbitrarily primed polymerase chain reaction for genotypic fingerprinting of P. gingivalis. DNA was extracted according to conventional methods. Ten-base oligonucleotide primers with arbitrary sequences were used with the polymerase chain reaction to amplify P. gingivalis genomic DNA. The amplification products were analyzed by agarose gel electrophoresis. The primer GACCGCTTGT grouped 73 P. gingivalis strains into 23 genotypes, including 16 genotypes containing a single strain each. The primer AGGGGTCTTG identified 45 different genotypes, 33 of which contained a single strain. P. gingivalis strains ATCC 33277T and 381 belonged to the same genotype. Likewise, strains W50 and W83 were of the same genetic clone. The present study indicates that the arbitrarily primed polymerase chain reaction represents a valuable and easy method for clonal analysis of P. gingivalis.

Bacterial Typing Techniques↗
PubMed1994

Molecular detection of Bacteroides forsythus in human periodontitis.

The usefulness of a digoxigenin-labeled genomic DNA probe for the detection of subgingival Bacteroides forsythus was examined. In addition, the arbitrarily primed polymerase chain reaction (AP-PCR) was used to delineate the genetic diversity of B. forsythus periodontal isolates. The DNA probe detected 10(3) B. forsythus cells and yielded a strong signal at 10(4) cells. It reacted with B. forsythus ATCC 43037T and 44 clinical isolates and showed no detectable reactivity with 75 strains of 24 other oral microbial species. In comparison to culture, the DNA probe in a dot-blot method demonstrated a sensitivity of 88.8% and a specificity of 38.4% (accuracy, 72.5%). By colony-blotting on primary plates, a sensitivity of 98.1% and a specificity of 53.8% (accuracy, 82.5%) were obtained. B. forsythus was detected in 449 (73.1%) of 614 periodontitis patients. The occurrence of the organism was closely associated with Porphyromonas gingivalis, both species being present in 54.8% and absent in 22.2% of 270 study samples. AP-PCR identified 24 B. forsythus genotypes among 27 test strains. This study demonstrated the utility of a non-radioactive genomic probe for direct detection of B. forsythus in subgingival specimens. The species showed a considerable degree of genetic diversity. DNA analysis may help to determine the role of B. forsythus in periodontal disease and its mode of transmission among exposed individuals.

Adolescent↗
PubMed1994

Absence of Helicobacter pylori in subgingival samples determined by polymerase chain reaction.

The polymerase chain reaction was used for the detection of Helicobacter pylori from subgingival plaque in 336 periodontitis patients. A pair of primers derived from the H. pylori urease gene A served to amplify a targeted 411-bp fragment of genomic DNA. This technique permitted the detection of as few as 60 H. pylori cells. Paper point samples from 3 deep periodontal pockets per patient were immersed in 1 ml of phosphate-buffered saline or distilled water, DNA was solubilized by detergent/protease method, 3.7 microliters or 37 microliters of lysate supernatant was used as template, and the amplification product was analyzed in 1% agarose gel containing ethidium bromide. Each experiment included purified DNA and cell lysate of H. pylori as positive controls. The presence of bacteria in the sample was verified by a primer pair common to prokaryote 16S rRNA. The present study did not reveal the specific polymerase chain reaction amplification product characteristic of H. pylori. We conclude that periodontal pockets do not constitute a natural reservoir for H. pylori.

Adult↗
PubMed1994

Attenuation of adenylate cyclase-induced increases in renal sodium excretion by the dopamine D-2 receptor agonist SK&F 89124.

1. Although the existence of D-2 receptor binding sites in kidney has been identified, their functional significance in terms of influencing renal sodium excretion is not clear. In the present study we have examined the renal effects of a selective D-2 receptor agonist, SK&F 89124, in anaesthetized rats. 2. Intravenous infusion of SK&F 89124 (0.3, 1 and 3 micrograms kg-1 min-1 respectively) produced dose-dependent decreases in mean arterial blood pressure, heart rate and renal blood flow without causing any significant changes in urine output, urinary sodium excretion, renal vascular resistance or glomerular filtration rate. The changes in blood pressure, heart rate and renal blood flow caused by SK&F 89124 were abolished by a selective D-2 receptor antagonist, domperidone (50 micrograms kg-1 i.v. bolus; 10 micrograms kg-1 min-1). 3; Treatment with 3-isobutyl-1-methylxanthine (IBMX, 1 mg kg-1 bolus i.v.) or forskolin (200 micrograms kg-1 bolus i.v.) produced increases in heart rate, urine output and urinary sodium excretion, but there was no change in mean blood pressure. The natriuretic and diuretic response, but not tachycardiac response to IBMX or forskolin, was attenuated by SK&F 89124 (0.3 micrograms kg-1 min-1). 4. These results suggest that the selective D-2 receptor agonist, SK&F 89124, produced a significant decrease in blood pressure and heart rate via prejunctional D-2 receptor-mediated inhibition of noradrenaline release from postganglionic sympathetic nerve terminals. Although activation of renal tubular D-2 receptors had no significant effect on renal excretory function under basal conditions, it is likely that these receptors may exert an opposing effect on cAMP-mediated increases in renal sodium and water excretion.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Investigation of computer lung model-predicted DLCO during single-breath maneuvers.

A computer model based on the theoretical gas absorption equations of Martonen and Wilson (J. Math. Biol. 14: 203-220, 1982) was developed to predict changes in single-breath diffusing capacity of the lung for carbon monoxide (DLCO) with alterations in anatomic dead space, alveolar volume, and inspiratory time. The computer model predictions were compared with results obtained from normal subjects performing DLCO maneuvers under correspondingly altered conditions to assess the validity of the Martonen-Wilson equations. In normal subjects, a theoretical "ideal" single-breath DLCO was derived from measured DLCO and adjusted to instantaneous inspiratory and expiratory times with this three-phase computer model. Clinical single-breath DLCO measurements with increased external dead space and inspiratory and expiratory times in normal subjects correlated well with our mathematical model predictions (all r > 0.80, P < 0.001) but did not correlate closely with the predicted effects of alveolar volume on DLCO. This study demonstrates that uniform gas absorption equations of Martonen and Wilson closely predict changes in observed DLCO with systematic variation of inspiratory and expiratory time in normal subjects at full lung volume and appear to be a reasonable estimation of normal physiological events during single-breath carbon monoxide absorption.

Adult↗
PubMed1994

Voltage-dependent potassium currents in ovine somatotrophs and their function in growth hormone secretion.

Sheep somatotroph-enriched cultures were obtained by means of enzyme dissociation and Percoll gradient separation. Nystatin-perforated-whole-cell recordings were performed on post-recording-identified somatotrophs after 4-14 days in vitro. Using Ca(2+)-free, tetrodotoxin-containing (1 microM) bath solution and K+ electrode solution, three types of voltage-dependent K+ currents were recorded as inward rectifying, outward transient and outward delayed rectifying K+ currents. The inward rectifying K+ current was very small at physiological extracellular K+ concentrations (5 mM) and enhanced by increasing the K+ concentration in the bath to 55 mM; it was blocked by tetraethylammonium (2 mM) but not by 4-aminopyridine (5 mM). A transient outward K+ current appeared at -50 mV and was selectively diminished by 4-aminopyridine (2 or 4 mM). A delayed rectifying outward K+ current was observed when the membrane potential was depolarized to -20 mV and was blocked by tetraethylammonium (2 mM) but not 4-aminopyridine (4 mM). Application of 4-aminopyridine but not tetraethylammonium (up to 5 mM) depolarized the cell membrane potential recorded under current clamp conditions and triggered action potentials when the bath solution contained Ca2+ (2 mM) but not tetrodotoxin. The intracellular Ca2+ concentration was increased by 4-aminopyridine as was growth hormone release. Therefore, the 4-aminopyridine-sensitive transient outward K+ current appears to be important in the determining the resting potential of ovine somatotrophs and plays a major role in regulating basal intracellular Ca2+ concentration and growth hormone secretion.

4-Aminopyridine↗
PubMed1994

Dynamics of mitral regurgitant flow and orifice area. Physiologic application of the proximal flow convergence method: clinical data and experimental testing.

BACKGROUND: The proximal flow convergence method, a quantitative color Doppler flow technique, has been validated recently for calculating regurgitant flow and orifice area. We investigated the potential of the method as a tool to study different pathophysiological mechanisms of mitral valve incompetence by assessing the time course of regurgitant flow and orifice area and analyzed the implications for quantification of mitral regurgitation. METHODS AND RESULTS: Fifty-six consecutive patients with mitral regurgitation of different etiologies were studied. The instantaneous regurgitant flow rate Q(t) was computed from color M-mode recordings of the proximal flow convergence region and divided by the corresponding orifice velocity V(t) to obtain the instantaneous orifice area A(t). Regurgitant stroke volume (RSV) was obtained by integrating Q(t). Mean regurgitant flow rate Qm was calculated by RSV divided by regurgitation time. Peak-to-mean regurgitant flow rates Qp/Qm and orifice areas Ap/Am were calculated to assess the phasic character of Q(t) and A(t). In the first 24 patients (group 1), computation of Qm and RSV from the color Doppler recordings was compared with the conventional pulsed Doppler method (r = .94, SEE = 29.4 mL/s and r = .95, SEE = 9.7 mL) as well as with angiography (rs = .93 and rs = .94, P < .001). The temporal variation of Q(t) and A(t) was studied in the next 32 patients (group 2): In functional regurgitation in dilated cardiomyopathy (n = 12), there was a constant decrease in A(t) throughout systole with an increase during left ventricular relaxation; Ap/Am was 5.49 +/- 3.17. In mitral valve prolapse (n = 6), A(t) was small in early systole, increasing substantially in midsystole, and decreasing mildly during left ventricular relaxation; Ap/Am was 2.48 +/- 0.26. In rheumatic mitral regurgitation (n = 14), a roughly constant regurgitant orifice area during most of systole was found in 4 patients. In the other patients there was significant variation of A (t) and the time of its maximum; Ap/Am was 1.81 +/- 0.56. ANOVA demonstrated that the differences in Ap/Am were related to the etiology of mitral regurgitation (P < .0001). To verify that the calculated variation in regurgitant orifice area during the cardiac cycle reflects an actual variation, the ability of the method to predict a constant orifice area throughout systole was tested experimentally in a canine model of mitral regurgitation. Five flow stages were produced by implanting fixed grommet orifices of different sizes into the anterior mitral leaflet. A constant regurgitant orifice area was correctly predicted throughout systole with a mean percent error of -1.8 +/- 4% (from -6.9% to +5.8%); the standard deviation of the individual curves calculated at 10% intervals during systole averaged 13.3% (from 3.6% to 19.6%). In addition, functional mitral regurgitation caused by ventricular dysfunction was produced pharmacologically in five dogs, and the color M-mode recordings of the proximal flow convergence region were obtained with the transducer placed directly on the heart instead of the chest, thus ruling out a significant effect of translational motion on the observed flow pattern. The pattern of regurgitant flow variation was identical to that observed in patients. CONCLUSIONS: The proximal flow convergence method demonstrates that regurgitant flow and orifice area vary throughout systole in distinct patterns characteristic of the underlying mechanism of mitral incompetence. Therefore, in addition to the potential of the method as a tool to quantify mitral regurgitation, it allows analysis of the pathophysiology of regurgitation in the individual patient, which may be helpful in clinical decision making. Calculating mitral regurgitant flow rate and volume from the time-varying proximal flow field (ie, without assuming a constant orifice area that would produce overestimation in individual patients) provides excellent agreement with independent te

Adult↗
PubMed1994

Intracardiac ultrasound measurement of volumes and ejection fraction in normal, infarcted, and aneurysmal left ventricles using a 10-MHz ultrasound catheter.

BACKGROUND: Our objective was to examine the accuracy of intracardiac ultrasound (ICUS) measurement of left ventricular (LV) volumes and ejection fraction (EF) using a 10-MHz ultrasound catheter. ICUS can image the LV in cross sections at all levels along the long axis with a transducer mounted on the tip of a catheter. Sequential serial LV cross-sectional images can be obtained during cardiac catheterization and used to calculate LV volumes by Simpson's rule. This technique may be an alternative to contrast LV angiography. METHODS AND RESULTS: A beating-heart in vivo model was created to measure LV volume directly and continuously with an intracavity high-compliance latex balloon connected to a calibrated extracardiac reservoir in eight dogs in 35 experimental stages. A 10F ICUS catheter with a 10-MHz single-element transducer was introduced retrogradely via the aortic valve to the apex. Series of sequential LV cross-sectional images were recorded from the apex to the base during a calibrated pullback of the catheter. At each 5-mm interval, the LV cross section was traced at end diastole and end systole. LV volume was calculated by Simpson's rule by integrating all segmental areas multiplied by segmental height. The effect on accuracy of selecting 5-, 10-, or 15-mm heights or a single section at the midventricular level for measurement was assessed. The influence of distorted ventricular shape on the accuracy of ICUS measurements of LV volume was evaluated. This method was applied in 19 experimental stages in 10 intact dogs and pigs catheterized via the femoral artery. In the in vivo canine model, LV end-diastolic volume, end-systolic volume, and EF determined by ICUS using 5-, 10-, or 15-mm segments were not different from the actual measurements. But correlation and agreement between ICUS end-diastolic volume and direct measurements for 5- and 10-mm segments were significantly better than for 15-mm segments or a single section. Similar excellent correlations and agreement were observed for actual and ICUS-derived end-systolic volumes using 5-, 10-, or 15-mm segments. The ICUS-derived EF correlated very well with actual EF with a small measurement error of 3.91 +/- 2.59% for 5-mm or 4.13 +/- 2.79% for 10-mm segments but a significantly greater measurement error for 15-mm segments (5.35 +/- 3.76%) or single sections (14.8 +/- 12.2%). The presence of LV infarction or aneurysm did not significantly influence the accuracy of ICUS calculations for segmental heights < or = 10 mm. Application in intact animals demonstrated a good correlation between stroke volume measured by ICUS and by thermodilution or flowmeter. ICUS-derived LV volumes correlated well with biplane angiographic volumes, with a tendency toward underestimation. There was no significant difference between ICUS-determined LV EF and EF determined by angiography. CONCLUSIONS: Intracardiac echocardiography accurately measures LV volumes and global systolic function in both regularly shaped and distorted left ventricles. This technique directly and continuously visualizes circumferential LV endocardium and wall thickness without contrast agents or geometric assumptions for calculation of LV volume. Thus, it should be particularly useful in patients at high risk for contrast-related complications or distorted LV shapes in which geometric assumptions may not be valid.

Animals↗
PubMed1994

Mechanism of compensatory hyperinsulinemia in normoglycemic insulin-resistant spontaneously hypertensive rats. Augmented enzymatic activity of glucokinase in beta-cells.

The cause of compensatory hyperinsulinemia in normoglycemic insulin-resistant states is unknown. Using spontaneously hypertensive rats (SHR), we tested the hypothesis that a lowered beta-cell set-point for glucose causes a hypersecretion of insulin at a normal glucose level. Islets isolated from normoglycemic hyperinsulinemic SHR were compared to age-matched (12 wk old) Wistar-Kyoto (WK) rats. The ED50 for glucose-induced insulin secretion was 6.6 +/- 1.0 mM glucose in SHR versus 9.6 +/- 0.5 mM glucose in WK (P < 0.02). Glucokinase enzymatic activity was increased 40% in SHR islets (P < 0.02) without any change in the glucokinase protein level by Western blot. The level of the beta-cell glucose transporter (GLUT-2) was increased 75% in SHR islets (P < 0.036). In summary, the beta-cell sensitivity for glucose was increased in these normoglycemic insulin resistant rats by an enhanced catalytic activity of glucokinase. We have identified a regulatory system for glucokinase in the beta-cell which entails variable catalytic activity of the enzyme, is modulated in response to variations in whole-body insulin sensitivity, and is not dependent on sustained changes in the plasma glucose level.

Animals↗
PubMed1994

Regulatory effects of glucose on the catalytic activity and cellular content of glucokinase in the pancreatic beta cell. Study using cultured rat islets.

Glucose regulates the cellular content of glucokinase in the pancreatic beta cell by altering the level of the enzyme. We investigated the existence of a second regulatory pathway, an alteration in the catalytic activity, by comparing Vmax and protein levels of glucokinase in rat islets cultured under high glucose conditions (16.7 mM) for 6, 14, and 24 h. The Vmax was increased by glucose at all time points. In contrast, glucokinase protein levels on Western blots were unchanged from the control value at 6 h but increased 40% at the later time points (P < 0.0002). Further evidence for a dual regulatory system was obtained with a reversal protocol. After a 6-h incubation at high glucose, an additional 3-h incubation at 5.5 mM glucose restored glucokinase Vmax to normal, but failed to change the Vmax after a 24-h incubation at high glucose. Finally, 10 microM cycloheximide partially prevented the increase in glucokinase Vmax induced by 24 h of high glucose, but had no effect at 6 h, suggesting the early increase in enzymatic activity did not require protein synthesis. In summary, glucose regulates both the catalytic activity and cellular content of glucokinase in the beta cell. Glucose-induced increases in glucokinase activity are an important element of the beta cell adaptive response to hyperglycemia.

Animals↗
PubMed1994

The impact of aprotinin on coronary artery bypass graft patency.

STUDY DESIGN: Aprotinin has recently been shown to reduce postoperative bleeding and transfusion requirements associated with coronary artery bypass grafting. One concern with its use, however, is that it may have a deleterious effect on graft patency because it promotes hemostasis. Forty-seven patients undergoing coronary artery bypass. Forty-seven patients undergoing coronary artery bypass grafting were enrolled in a prospective, randomized double-blind trial of aprotinin to determine the effect of this agent on postoperative bleeding, transfusion requirements, renal function, and graft patency. The study group was comprised of the 32 patients who underwent technically adequate ultrafast CT scans 6 to 8 weeks postoperatively to determine graft patency. Sixteen patients received aprotinin (aprotinin group) and 16 received placebo (control group). RESULTS: Demographic and operative descriptors were comparable between groups. Postoperative mediastinal and chest tube drainage in the aprotinin group was significantly less than that in the control group (722 vs 1,540 mL; p = 0.0006) and the mean blood transfusion requirements were less, but this did not reach significance (125 vs 297 mL; p = 0.42). Analysis of graft patency by patients revealed that 5 patients in the aprotinin group (31%) had at least one occluded graft, while none of the patients in the control group had an occluded graft (p = 0.04). Analysis by graft revealed that 38 of 43 grafts placed in the aprotinin group were patent, while all 38 grafts placed in the placebo group were patent (88.4 vs 100%; p = 0.057). There was no difference in the incidence of myocardial infarction, renal dysfunction or hematologic indexes at discharge between the groups, or evidence of other thrombotic complications. CONCLUSION: We conclude that high-dose aprotinin is effective in reducing hemorrhage after coronary artery bypass grafting. However, its routine use should be approached cautiously due to its possible adverse effects on graft patency.

Aged↗
PubMed1994

The effect of GH-releasing peptide-2 (GHRP-2 or KP 102) on GH secretion from primary cultured ovine pituitary cells can be abolished by a specific GH-releasing factor (GRF) receptor antagonist.

A newly synthesised GH-releasing peptide, KP 102 (also named GHRP-2), was studied in an in vitro perifusion system of primary cultured ovine anterior pituitary cells. Application of KP 102 to the perifusion medium caused a dose-dependent increase in GH secretion. Dose-response relationships indicated that KP 102 had similar potency to GRF and was 10-fold more potent than earlier generations of GH-releasing peptide (GHRP-6 and GHRP-1) tested in same system. The response to a second application of KP 102 given within 1 h of initial application was significantly lower than the response to the first application. When KP 102 (or GRF) was applied first and then GRF (or KP 102) given 1 h later, the second response was not attenuated. When GRF and KP 102 were coadministered, an additive effect on release of GH was obtained. The effect of maximal dose of KP 102 (100 nM) on GH release was totally abolished by [Ac-Tyr1,D-Arg2] GRF 1-29 (1 microM) which is believed to be a specific antagonist for the GRF receptor. Blockade of Ca2+ channels by Cd2+ (2 mM) diminished the basal GH secretion and abolished the increase in GH release in response to KP 102 (100 nM). These data suggest that the action of KP 102 is blocked by a GRF receptor antagonist and therefore acts through a different receptor to that employed by earlier generations of GH-releasing peptides. GH release in response to KP 102 involves an increase in Ca2+ influx and there is no cross-desensitization between KP 102 and GRF responses.

Animals↗
PubMed1994

Diazoxide causes recovery of beta-cell glucose responsiveness in 90% pancreatectomized diabetic rats.

Chronic hyperglycemia causes near-total disappearance of glucose-induced insulin secretion. The etiology has been suggested to be a nonsustainable stimulation of insulin release that causes beta-cells to become unresponsive to glucose through an undefined mechanism. We used an inhibitor of insulin secretion, diazoxide, to test this hypothesis in 90% pancreatectomized (Px) rats. Px rats were given 5 days of diazoxide (30 mg/kg orally twice a day) or tap water starting on postoperative day 8, 15, or 22. In vitro pancreas perfusions were conducted 36 h posttreatment (2, 3, or 4 weeks after surgery) using a protocol of 15 min of 16.7 mM glucose followed by 15 min of 16.7 mM glucose plus 10 mM arginine. In 2-week Px rats, insulin responses to 16.7 mM glucose and to glucose/arginine were both appropriate for the reduced beta-cell mass, i.e., no defect in beta-cell glucose responsiveness had yet occurred. Diazoxide had no affect on insulin release at this time. Between 2 and 3 weeks after pancreatectomy, insulin output to 16.7 mM glucose fell 75%, and that to glucose/arginine fell 50%. Diazoxide given at this time partially blocked the fall in glucose-induced insulin secretion and totally prevented that with arginine. The increased insulin secretion caused by diazoxide was accompanied by 1) lower nonfasting plasma glucose values, 2) improved glucose tolerance after oral glucose load, and 3) a 50% increase in pancreatic insulin content. Our results support the concept that excessive insulin secretion is a major cause of the hyperglycemia-induced loss of beta-cell glucose responsiveness. A leading candidate for the mechanism of this effect is depleted pancreatic insulin stores. Overstimulation of insulin secretion provides a new target for pharmacological therapy aimed at reducing glucose intolerance in non-insulin-dependent diabetes mellitus.

Animals↗
PubMed1994

Increased catalytic activity of glucokinase in isolated islets from hyperinsulinemic rats.

The high Km glucose phosphorylation enzyme glucokinase is believed to be the beta-cell glucose sensor, i.e., the site in glucose metabolism that determines the sensitivity and specificity of glucose-induced insulin secretion. We investigated the regulation of this enzyme by measuring glucokinase Vmax and protein levels in isolated islets from hyperinsulinemic rats. Rats were infused for 48 h with 2 ml/h of 20% glucose, 50% glucose, or 0.45% NaCl (control rats). At the end of the infusion, 20% glucose-infused rats were normoglycemic and hyperinsulinemic (2.3-fold rise in basal plasma insulin level). Their islets had a 2.3-fold increase in insulin secretion at 8.3 mM glucose (51 +/- 10% of capacity vs. 22 +/- 5% in NaCl rats, P < 0.03), a 75% increase in glucokinase Vmax and little if any increase in glucokinase protein level (111 +/- 3% of control). The rats infused with 50% glucose had marked hyperglycemia and higher basal plasma insulin levels. Their islets were maximally stimulated by 8.3 mM glucose in combination with a 270% increase in glucokinase Vmax and a 69 +/- 11% increase in glucokinase protein level. Hexokinase Vmax was also doubled. Thus, compensatory increases in beta-cell glucose phosphorylation are a key mechanism for adaptive hyperinsulinemia. Our results show two types of regulation for the beta-cell high Km phosphorylation enzyme, glucokinase. The content of glucokinase protein is controlled by the plasma glucose level. Variable catalytic activity of this protein was also observed in this study.

Animals↗
PubMed1994

Lack of renal dopamine production during acute volume expansion in Dahl salt-sensitive rats.

Endogenous kidney dopamine (DA) is reported to contribute to the natriuretic response to acute volume expansion (VE). Several studies suggest that a defect in renal DA-ergic system may play a role in genetic hypertension in humans and rats. The present study was performed to determine the role of renal DA and tubular DA-1 receptors in the natriuretic response to VE in age-matched inbred Dahl salt sensitive (SS/Jr) and salt resistant (SR/Jr) rats of 9-11 weeks of age. In pentobarbital anesthetized rats, VE was carried out by intravenous infusion of isotonic sodium chloride (5% body weight) over a period of 60 min. This maneuver evoked marked increases in urine output and urinary sodium excretion in both SR/Jr and SS/Jr species. However, the natriuretic and diuretic response to VE was significantly reduced in SS/Jr as compared to SR/Jr rats. It was also observed that the urinary excretion of DA was significantly increased during VE only in SR/Jr, but not in SS/Jr rats. In separate group of animals, infusion of DA (1 microgram/kg/min) produced similar increases in urine output and urinary sodium excretion without causing any alterations in blood pressure or heart rate in either SS/Jr or SR/Jr rats. These results suggest that SS/Jr rats are not able to eliminate an acute increase in sodium load as efficiently as SR/Jr, which may be partly due to an impaired endogenous kidney DA production.

Animals↗