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PubMed2005

[Differences in cardiac troponin I and T levels measured in asymptomatic hemodialysis patients with last generation immunoassays].

Previous studies reported cardiac troponin I (cTnI) and T (cTnT) levels to be higher than normal in a significant proportion of asymptomatic chronic hemodialysis (HD) patients without evidence of acute myocardial injury. We have therefore evaluated in such patients the accuracy of cTnI and cTnT determinations measured with last generation assays. Fifty chronic HD patients (34 males) without symptoms of acute myocardial ischemia were studied. Their mean age (+/-SD) was 64.4+/-12.7 years, 22 patients (44%) had an history of cardiac ischemic disease and 19 (38%) were diabetics. Serum cardiac markers were measured with last generation assays before and after a single HD session and in a control group including 30 hospitalized patients without renal failure. The cTnI were determined with Dimension RxL "Improved method" assay (Dade Behring), the cTnT with Elecys "Third generation" assay (Roche Diagnostics) and the creatine kinase (CK) with Integra (Roche Diagnostics). The cTnI were also simultaneously determined with the assay previously used at our institution (Dimension RxL, Dade Behring), indicated as old-method-cTnI. With the last generation assay only 1 patient (2%) had elevated cTnI (>0.1 microg/l) in the study group compared to none in the control group (P=NS). Instead, with the old-method-cTnI assay 11 patients (22%) had elevated (>0.3 microg/l) predialysis cTnI levels (P<0.01 compared to the "Improved method" assay). The predialysis cTnT levels were higher than normal (>0.1 microg/l) in 23 patients (46%), compared to none in the control group (P<0.01). The CK levels were elevated (>170 IU/L) in 4 dialysis patients (8%) compared to one (3,3%) in the control group (P=NS). The cTnT levels slightly but non-significantly diminished during dialysis (from 0.102+/-0.070 to 0.085+/-0.067 mug/l, P=NS), while in the same time no changes were observed for cTnI and CK levels. In conclusion, the specificity of cTnI determinations in HD patients is greatly improved by the last generation assay (from 78 to 98%), and is actually similar to that observed in a population with normal renal function. Therefore cTnI, determined with the last generation assay used in the present study, can be reliably used for the diagnosis of acute coronary syndromes in HD patients. Instead, cTnT levels remain higher than normal in a significant proportion of asymptomatic HD patients (46%) and the reasons for this fact need further investigations.

Aged↗
PubMed2004

Exposure to hypomagnetic field space for multiple generations causes amnesia in Drosophila melanogaster.

This is the introduction of Drosophila into the study of learning and memory affected by removal of the geomagnetic field (GMF) for successive generations. Using the operant visual learning/memory paradigm at a flight simulator, the present study revealed that wild-type flies raised in a hypomagnetic field environment continuously for 10 successive generations were gradually impaired in visual conditioning learning and memory formation and finally the 10th generation flies became morphs of nonlearners and completely amnesiac. The control experiments show that the impairment could not be ascribed to any apparent sensorimotor problems in Drosophila. The reverse shift from hypomagnetic field (HMF) to natural GMF restored the GMF-free induced amnesia fully after six consecutive generations. Thus, our findings demonstrate conclusively that some serious, but reversible learning and memory impairment may occur for living organisms in a prolonged separation from GMF over many consecutive generations. And Drosophila has the potential to develop into a new model organism for the study of the neurobiology of magnetism for multiple generations.

Amnesia↗
PubMed2004

Receptor mechanisms mediating cyanide generation in PC12 cells and rat brain.

Cyanide is generated in neurons and this report examines the two different receptors which mediate cyanide formation in neuronal tissue. An opiate receptor blocked by naloxone increases cyanide production both in rat brain and in rat pheochromocytoma (PC12) cells. A muscarinic receptor in PC12 cells releases cyanide and the effect is blocked by atropine. In rat brain, in vivo, a muscarinic agonist inhibits cyanide generation, possibly by acting on receptor subtypes different from those in PC12 cells. Cyanide generation by a muscarinic agonist in PC12 cells is blocked by pertussis toxin but that caused by an opiate is not. Thus, two different receptors and two different second messenger systems can mediate cyanide generation in PC12 cells. In parallel with the in vivo data, cultured primary rat cortical cells also show decreased cyanide release following muscarinic stimulation. Both blockade of cyanide generation by muscarinic receptor activation and cyanide release by opiate agonists from cortical cells are pertussis toxin insensitive. Similarly, little cyanide generation was seen following cholera toxin treatment. These data indicate that opiate receptors increase and muscarinic receptors decrease cyanide production in rat brain tissue by G-protein independent mechanisms. This work supports the suggestion that the powerful actions of cyanide may be important for neuromodulation in the CNS.

Analysis of Variance↗
PubMed2005

Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite.

Denitrifying bacteria in soil generate nitric oxide (NO) from nitrite as a part of the nitrogen cycle, but little is known about NO production by commensal bacteria. We used a chemiluminescence assay to explore if human faeces and different representative gut bacteria are able to generate NO. Bacteria were incubated anaerobically in gas-tight bags, with or without nitrate or nitrite in the growth medium. In addition, luminal NO levels were measured in vivo in the intestines in germ-free and conventional rats, and in rats mono-associated with lactobacilli. We show that human faeces can generate NO after nitrate or nitrite supplementation. Lactobacilli and bifidobacteria generated much NO from nitrite, but only a few of the tested strains produced NO from nitrate and at much lower levels. In contrast, Escherichia coli, Bacteroides thetaiotaomicron, and Clostridium difficile did not produce significant amounts of NO either with nitrate or nitrite. NO generation in the gut lumen was also observed in vivo in conventional rats but not in germ-free rats or in rats mono-associated with lactobacilli. We conclude that NO can be generated by the anaerobic gut flora in the presence of nitrate or nitrite. Future studies will reveal its biological significance in regulation of gastrointestinal integrity.

Adult↗
PubMed2004

Acceleration of superoxide generation in polymorphonuclear leukocytes and inhibition of platelet aggregation by alk(en)yl thiosulfates derived from onion and garlic in dogs and humans.

We recently identified sodium n-propyl thiosulfate (NPTS) and sodium 2-propenyl thiosulfate (2PTS) from boiled onion and garlic, respectively, as causative agents of hemolytic anemia in dogs. We present here data concerning the effects of these alk(en)yl thiosulfates on superoxide (O(2)(-)) generation in peripheral polymorphonuclear leukocytes (PMNs) and on adenosine 5'-diphosphate (ADP)-induced platelet aggregation in dogs and humans in vitro. Both NPTS and 2PTS increased O(2)(-) generation significantly (P<0.05 at 1mM NPTS, P<0.005 at 0.1 and 1mM 2PTS) and reduced its reaction time significantly (P<0.05 between 0.01 and 1mM NPTS and at 1mM 2PTS) in canine PMNs stimulated by phorbol 12-myristate 13-acetate, compared with the control without alk(en)yl thiosulfates. However, a tendency to return to the control level was observed at 10mM of the alk(en)yl thiosulfates in both O(2)(-) generation and its reaction time. Although NPTS and 2PTS did not exert any significant effect on the O(2)(-) generation in human PMNs, 2PTS reduced its reaction time significantly (P<0.05) at 1 and 10mM compared with the control, showing that 2PTS accelerated O(2)(-) generation in human PMNs. The difference in effects on O(2)(-) generation may be due to that in susceptibility to alk(en)yl thiosulfates between canine and human PMNs. On the other hand, NPTS and 2PTS were shown to significantly inhibit ADP-induced platelet aggregation at 0.01mM (P<0.01) in canine platelets and at 0.001-0.1mM (P<0.05) in human platelets. In contrast, the maximal aggregation percentage returned to the control level at 1mM of alk(en)yl thiosulfates in both canine and human platelets. From these results, we conclude that NPTS and 2PTS have the potential to promote immune functions and prevent cardiovascular diseases.

Adenosine Diphosphate↗
PubMed2006

Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin.

Free radicals/reactive oxygen species (ROS) generated in skin by UV irradiation were measured by electron spin resonance (ESR). To increase the sensitivity of measurement the short life free radicals/ROS were scavenged and accumulated by using the nitroxyl probe 3-carboxy-2,2,5,5-tetrametylpyrrolidine-1-oxyl (PCA). The spatial distribution of free radicals/ROS measured in pig skin biopsies with ESR imaging after UV irradiation corresponds to the intensity decay of irradiance in the depth of the skin. The main part of free radicals/ROS were generated by UVA (320-400 nm) so that the spatial distribution of free radicals reaches up to the lower side of the dermis. In vivo measurements on human skin were performed with a L-band ESR spectrometer and a surface coil integrating the signal intensities from all skin layers to get a sufficient signal amplitude. Using this experimental arrangement the protection of UVB and UVA/B filter against the generation of free radicals/ROS in skin were measured. The protection against ROS and the repair of damages caused by them can be realized with active antioxidants characterized by a high antioxidative power (AP). The effect of UV filter and antioxidants corresponding to their protection against free radicals/ROS in skin generated by UVAB irradiation can be quantified by the new radical sun protection factor (RSF). The RSF indicates the increase of time for staying in the sun to generate the same number of free radicals/ROS in the skin like for the unprotected skin. Regarding the amount of generated free radicals/ROS in skin as an biophysical endpoint the RSF characterizes both the protection against UVB and UVA radiation.

Animals↗
PubMed2006

Iron release and ROS generation from mineral particles are not related to cytokine release or apoptosis in exposed A549 cells.

The generation of reactive oxygen species (ROS) by mineral particles is believed to be central to their toxicity and their ability to induce inflammation. Surface bound or soluble iron may contribute to the particle-effects by enhancing the ROS generation through the Fenton reaction. Nevertheless, the importance of ROS and transition metals to mineral particle-induced effects is still unclear and further investigations are needed. In the present study we have investigated different mineral particles for their total iron content, amount of soluble iron at pH 7.0 and 4.0, their ability to generate ROS in a cell-free environment, and their ability to induce cytokine release and apoptosis in a human alveolar epithelial cell line (A549). All the investigated parameters varied considerably between the different particles, with the exception of ability to induce apoptosis. Total iron content did not reflect the amount of soluble iron, and neither total nor soluble iron was correlated with ROS generation. Moreover, iron content and ROS was not correlated with the ability of particles to induce cytokine release or apoptosis. The present results suggest that there is no clear relationship between the particles iron content and ability to generate ROS. Moreover, neither iron content nor the ability to induce ROS generation appears to be a prerequisite for the inflammatory potential or cytotoxicity of mineral particles.

Air Pollutants↗
PubMed2005

Forecasting municipal solid waste generation in a fast-growing urban region with system dynamics modeling.

Both planning and design of municipal solid waste management systems require accurate prediction of solid waste generation. Yet achieving the anticipated prediction accuracy with regard to the generation trends facing many fast-growing regions is quite challenging. The lack of complete historical records of solid waste quantity and quality due to insufficient budget and unavailable management capacity has resulted in a situation that makes the long-term system planning and/or short-term expansion programs intangible. To effectively handle these problems based on limited data samples, a new analytical approach capable of addressing socioeconomic and environmental situations must be developed and applied for fulfilling the prediction analysis of solid waste generation with reasonable accuracy. This study presents a new approach--system dynamics modeling--for the prediction of solid waste generation in a fast-growing urban area based on a set of limited samples. To address the impact on sustainable development city wide, the practical implementation was assessed by a case study in the city of San Antonio, Texas (USA). This area is becoming one of the fastest-growing regions in North America due to the economic impact of the North American Free Trade Agreement (NAFTA). The analysis presents various trends of solid waste generation associated with five different solid waste generation models using a system dynamics simulation tool--Stella. Research findings clearly indicate that such a new forecasting approach may cover a variety of possible causative models and track inevitable uncertainties down when traditional statistical least-squares regression methods are unable to handle such issues.

Cities↗
PubMed2005

Electricity generation from cysteine in a microbial fuel cell.

In a microbial fuel cell (MFC), power can be generated from the oxidation of organic matter by bacteria at the anode, with reduction of oxygen at the cathode. Proton exchange membranes used in MFCs are permeable to oxygen, resulting in the diffusion of oxygen into the anode chamber. This could either lower power generation by obligate anaerobes or result in the loss in electron donor from aerobic respiration by facultative or other aerobic bacteria. In order to maintain anaerobic conditions in conventional anaerobic laboratory cultures, chemical oxygen scavengers such as cysteine are commonly used. It is shown here that cysteine can serve as a substrate for electricity generation by bacteria in a MFC. A two-chamber MFC containing a proton exchange membrane was inoculated with an anaerobic marine sediment. Over a period of a few weeks, electricity generation gradually increased to a maximum power density of 19 mW/m(2) (700 or 1000 Omega resistor; 385 mg/L of cysteine). Power output increased to 39 mW/m(2) when cysteine concentrations were increased up to 770 mg/L (493 Omega resistor). The use of a more active cathode with Pt- or Pt-Ru, increased the maximum power from 19 to 33 mW/m(2) demonstrating that cathode efficiency limited power generation. Power was always immediately generated upon addition of fresh medium, but initial power levels consistently increased by ca. 30% during the first 24 h. Electron recovery as electricity was 14% based on complete cysteine oxidation, with an additional 14% (28% total) potentially lost to oxygen diffusion through the proton exchange membrane. 16S rRNA-based analysis of the biofilm on the anode of the MFC indicated that the predominant organisms were Shewanella spp. closely related to Shewanella affinis (37% of 16S rRNA gene sequences recovered in clone libraries).

Bacterial Physiological Phenomena↗
PubMed2003

Generational diversity--the Nexters.

For the first time in recent history, the workforce includes four generations of employees--Veterans, Baby Boomers, Generation Xers, and Nexters. These generations share some common values and beliefs, but they also exhibit differences stemming from the experiences of their eras. Understanding and appreciating these differences will help decrease generational conflict and support all generations in welcoming diversity. The Nexter generation includes more than 81 million people, approximately 30% of the current population. Nexters will enter the workforce in large numbers and will influence changes in the work environment just as Baby Boomers did.

Adult↗
PubMed1999

Risk of venous thromboembolism with third-generation oral contraceptives: A review.

Recent data indicate that users of third-generation oral contraceptives, those containing the new progestins desogestrel, gestodene, and norgestimate, have 2 to 3 times the risk of venous thromboembolism faced by users of second-generation oral contraceptives. The risk of development of deep vein thrombosis was also found to be 2 to 5 times greater with a low-estrogen, desogestrel-containing oral contraceptive than with second-generation monophasic and triphasic preparations. Investigators point to an acquired resistance to the anticoagulation effects of activated protein C, the most common cause of hereditary thrombophilia, as a possible mechanism. The American College of Obstetrics and Gynecology's Committee on Gynecologic Practice reconfirms the increased risk of venous thromboembolism associated with third-generation progestins versus other progestins. Because the third-generation oral contraceptives may have benefit for some patients, however, it defers to the individual clinician's and patient's judgment regarding the use of a desogestrel-containing formulation (the only third-generation progestin available in the United States).

Clinical Trials as Topic↗
PubMed1993

Randomized, prospective comparison of first- and second-generation cephalosporins as infection prophylaxis for cardiac surgery.

Surgical wound infections after cardiovascular surgery may be life threatening and are resource intensive. Second-generation cephalosporins are purported to have a broader antimicrobial spectrum than first-generation cephalosporins and, therefore, may be more efficacious for infection prophylaxis. We have conducted a randomized prospective study of 702 patients undergoing open heart surgery to test the hypothesis that the second-generation cephalosporin, cefuroxime, will be more efficacious for infection prophylaxis than the first-generation cephalosporin, cefazolin. Patients were randomized to receive cefazolin 1 g intravenously every 8 hours for 48 hours begun 1 hour preoperatively plus 1 g after 4 hours of surgery (8 doses, n = 425) or cefuroxime 1.5 g 1 hour prior to surgery plus 1.5 g every 12 hours for 3 additional doses (4 doses, n = 277). Infection was defined as a draining wound with or without a positive culture. There was no difference in the wound infection rate between the groups (p = 0.68). Chest wound infections occurred in 2.1% of patients treated with cefazolin and 2.9% of patients treated with cefuroxime (p = 0.79). The rate of true mediastinitis requiring exploration and drainage was 0.7% in both groups (p = 0.084). Leg infections occurred in 6.6% of cefazolin-treated patients and 5.6% of cefuroxime-treated patients (p = 0.83). The second-generation cephalosporin, cefuroxime, did not reduce the incidence of wound infection when compared with the first-generation cephalosporin, cefazolin. Since institutional antibiotic acquisition and administration costs vary, careful analysis of these factors will allow determination of the most cost-effective infection prophylaxis regimen in cardiac surgery.

Cardiac Surgical Procedures↗
PubMed1996

Treatment of avascular ulcers with cytokine-induced tissue generation and skin grafting.

BACKGROUND: Recombinant platelet-derived growth factor (rPDGF-BB) stimulates migration and proliferation of fibroblasts and smooth muscle cells and induces the rapid development of granulation tissue. This study investigated the use of rPDGF-BB and skin grafting to heal avascular ulcers using a rabbit model. We further investigated the effect of a hyaluronic acid carrier and a vascular pedicle on rPDGF-induced tissue generation in this model. METHODS: Large avascular ulcers were created on both ears of New Zealand white rabbits. One ulcer was treated with topical rPDGF-BB, the other with control buffer. After 5 or 7 days, the amount of granulation tissue migration from the wound margin was measured, and the wounds were skin grafted. In another group of ulcers, rPDGF-BB treatment was combined with a hyaluronic acid disk or an intact central axial ear artery and vein. RESULTS: Whereas control wounds generated 1.00 +/- 0.27 mm and 1.75 +/- 0.25 mm of granulated tissue migration from the wound margin by days 5 and 7, respectively, rPDGF-BB treatment increased the amount of granulation tissue migration to 1.88 +/- 0.23 mm and 3.00 +/- 0.86 mm by days 5 and 7 after treatment, respectively (P <0.05 at both time points). Hyaluronic acid disks stimulated 2.50 +/- 0.22 mm of granulation tissue migration by day 7 in controls; when rPDGF-BB was added to the carrier, the migration increased to 4.50 +/- 0.29 mm from the wound margin (P<0.05). Granulation tissue migration was further increased with an intact vascular pedicle: 5.75 +/- 0.48 mm in controls versus 7.75 +/- 0.25 mm with rPDGF-BB treatment (P<0.01). Skin grafts applied to the treated ulcers failed to survive in all groups except those with intact vascular pedicles. CONCLUSIONS. This study demonstrates that rPDGF-BB can increase the amount of granulation tissue generated over an avascular wound. This tissue generation is enhanced by both a hyaluronic acid carrier and a vascular pedicle. A vascular pedicle was required for skin graft survival. This study supports the role of hyaluronic acid in rPDGF-BB induced tissue generation and the requirement of a direct blood supply for functional cytokine-induced tissue generation.

Animals↗
PubMed1987

Generation of H2O2 is regulated by cytoplasmic free calcium in cultured porcine thyroid cells.

Effects of calcium ionophore A23187 and BAY-K-8644, a calcium channel agonist, on cytoplasmic free calcium ([Ca2+]i) and H2O2 generation were studied in cultured porcine thyroid cells. We monitored continuously the effects of A23187 and BAY-K-8644 on [Ca2+]i and H2O2 generation, using the intracellularly trapped fluorescent Ca2+ indicator, fura-2, and homovanillic acid, respectively. A23187 and BAY-K-8644 induce an immediate increase in [Ca2+]i and H2O2 generation. The A23187- and BAY-K-8644-induced [Ca2+]i responses and H2O2 generation occur immediately, reach a maximum within several seconds, and then slowly decline. The minimum doses of A23187 or BAY-K-8644 to increase [Ca2+]i stimulate H2O2 generation. H2O2 generation is regulated by [Ca2+]i.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

A kinetic model of vertebrate 20S proteasome accounting for the generation of major proteolytic fragments from oligomeric peptide substrates.

There is now convincing evidence that the proteasome contributes to the generation of most of the peptides presented by major histocompatibility complex class I molecules. Here we present a model-based kinetic analysis of fragment patterns generated by the 20S proteasome from 20 to 40 residues long oligomeric substrates. The model consists of ordinary first-order differential equations describing the time evolution of the average probabilities with which fragments can be generated from a given initial substrate. First-order rate laws are used to describe the cleavage of peptide bonds and the release of peptides from the interior of the proteasome to the external space. Numerical estimates for the 27 unknown model parameters are determined across a set of five different proteins with known cleavage patterns. Testing the validity of the model by a jack knife procedure, about 80% of the observed fragments can be correctly identified, whereas the abundance of false-positive classifications is below 10%. From our theoretical approach, it is inferred that double-cleavage fragments of length 7-13 are predominantly cut out in "C-N-order" in that the C-terminus is generated first. This is due to striking differences in the further processing of the two fragments generated by the first cleavage. The upstream fragment exhibits a pronounced tendency to escape from second cleavage as indicated by a large release rate and a monotone exponential decline of peptide bond accessibility with increasing distance from the first scissile bond. In contrast, the release rate of the downstream fragment is about four orders of magnitude lower and the accessibility of peptide bonds shows a sharp peak in a distance of about nine residues from the first scissile bond. This finding strongly supports the idea that generation of fragments with well-defined lengths is favored in that temporary immobilization of the downstream fragment after the first cleavage renders it susceptible for a second cleavage.

Adenosine Triphosphatases↗
PubMed2002

The biochemical kinetics underlying actin movement generated by one and many skeletal muscle myosin molecules.

To better understand how skeletal muscle myosin molecules move actin filaments, we determine the motion-generating biochemistry of a single myosin molecule and study how it scales with the motion-generating biochemistry of an ensemble of myosin molecules. First, by measuring the effects of various ligands (ATP, ADP, and P(i)) on event lifetimes, tau(on), in a laser trap, we determine the biochemical kinetics underlying the stepwise movement of an actin filament generated by a single myosin molecule. Next, by measuring the effects of these same ligands on actin velocities, V, in an in vitro motility assay, we determine the biochemistry underlying the continuous movement of an actin filament generated by an ensemble of myosin molecules. The observed effects of P(i) on single molecule mechanochemistry indicate that motion generation by a single myosin molecule is closely associated with actin-induced P(i) dissociation. We obtain additional evidence for this relationship by measuring changes in single molecule mechanochemistry caused by a smooth muscle HMM mutation that results in a reduced P(i)-release rate. In contrast, we observe that motion generation by an ensemble of myosin molecules is limited by ATP-induced actin dissociation (i.e., V varies as 1/tau(on)) at low [ATP], but deviates from this relationship at high [ATP]. The single-molecule data uniquely provide a direct measure of the fundamental mechanochemistry of the actomyosin ATPase reaction under a minimal load and serve as a clear basis for a model of ensemble motility in which actin-attached myosin molecules impose a load.

Actomyosin↗
PubMed1995

Parallel inhibition of active force and relaxed fiber stiffness by caldesmon fragments at physiological ionic strength and temperature conditions: additional evidence that weak cross-bridge binding to actin is an essential intermediate for force generation.

Previously we showed that stiffness of relaxed fibers and active force generated in single skinned fibers of rabbit psoas muscle are inhibited in parallel by actin-binding fragments of caldesmon, an actin-associated protein of smooth muscle, under conditions in which a large fraction of cross-bridges is weakly attached to actin (ionic strength of 50 mM and temperature of 5 degrees C). These results suggested that weak cross-bridge attachment to actin is essential for force generation. The present study provides evidence that this is also true for physiological ionic strength (170 mM) at temperatures up to 30 degrees C, suggesting that weak cross-bridge binding to actin is generally required for force generation. In addition, we show that the inhibition of active force is not a result of changes in cross-bridge cycling kinetics but apparently results from selective inhibition of weak cross-bridge binding to actin. Together with our previous biochemical, mechanical, and structural studies, these findings support the proposal that weak cross-bridge attachment to actin is an essential intermediate on the path to force generation and are consistent with the concept that isometric force mainly results from an increase in strain of the attached cross-bridge as a result of a structural change associated with the transition from a weakly bound to a strongly bound actomyosin complex. This mechanism is different from the processes responsible for quick tension recovery that were proposed by Huxley and Simmons (Proposed mechanism of force generation in striated muscle. Nature. 233:533-538.) to represent the elementary mechanism of force generation.

Actins↗
PubMed1999

Effects of glucose and related substrates on the recovery of the electrical activity of gonadotropin-releasing hormone pulse generator which is decreased by insulin-induced hypoglycemia in the estrogen-primed ovariectomized rat.

We investigated the effect of glucose and its related substrates on the recovery of pulsatile luteinizing hormone (LH) secretion which was suppressed by insulin in estrogen-primed ovariectomized rats. We also examined the effect of glucose on the electrical activity of the gonadotropin-releasing hormone (GnRH) pulse generator which was suppressed by insulin. The intravenous (i.v.) injection of insulin (5 units/rat) suppressed the pulsatile LH secretion for 3 h in estrogen-primed ovariectomized rats. This suppressive effect of insulin on the LH secretion was rapidly reversed by the i.v. injection of glucose and mannose but not by the injection of lactate and saline. Fructose could recover the LH secretion suppressed by insulin, but took a longer time than glucose did. By monitoring the electrical activity of the GnRH pulse generator, we found that i.v. injection of insulin suppressed the pulsatile LH secretion by decreasing the activity of the GnRH pulse generator. Again, the i.v. injection of glucose, but not saline, immediately recovered the decrease in the electrical activity of the GnRH pulse generator. Fructose could recover the activity of the GnRH pulse generator, but it took a longer time than glucose did. We suggest that glucose availability, but not simply a metabolic state such as the ATP level, is an essential factor for maintaining the electrical activity of the GnRH pulse generator which is responsible for pulsatile LH secretion.

Animals↗