Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 739 records · Page 41Linked to original sources

PubMed1999

Isolation, cloning, and expression of an acid phosphatase containing phosphotyrosyl phosphatase activity from Prevotella intermedia.

A novel acid phosphatase containing phosphotyrosyl phosphatase (PTPase) activity, designated PiACP, from Prevotella intermedia ATCC 25611, an anaerobe implicated in progressive periodontal disease, has been purified and characterized. PiACP, a monomer with an apparent molecular mass of 30 kDa, did not require divalent metal cations for activity and was sensitive to orthovanadate but highly resistant to okadaic acid. The enzyme exhibited substantial activity against tyrosine phosphate-containing peptides derived from the epidermal growth factor receptor. On the basis of N-terminal and internal amino acid sequences of purified PiACP, the gene coding for PiACP was isolated and sequenced. The PiACP gene consisted of 792 bp and coded for a basic protein with an M(r) of 29,164. The deduced amino acid sequence exhibited striking similarity (25 to 64%) to those of members of class A bacterial acid phosphatases, including PhoC of Morganella morganii, and involved a conserved phosphatase sequence motif that is shared among several lipid phosphatases and the mammalian glucose-6-phosphatases. The highly conservative motif HCXAGXXR in the active domain of PTPase was not found in PiACP. Mutagenesis of recombinant PiACP showed that His-170 and His-209 were essential for activity. Thus, the class A bacterial acid phosphatases including PiACP may function as atypical PTPases, the biological functions of which remain to be determined.

Acid Phosphatase↗

PubMed1999

Primary virus envelope cross-reactivity of the broadening neutralizing antibody response during early chronic human immunodeficiency virus type 1 infection.

To test the hypothesis that changing neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1) during chronic infection were a response to emergence of neutralization escape mutants, we cloned expressed and characterized envelope clones from patients in the Multicenter AIDS Cohort Study (MACS). Pseudotyped HIV-1 envelope clones obtained from differing time points were assessed for sensitivity to neutralization by using sera from different times from the same and different patients. Clones from early and late time points during chronic infection had similar neutralization sensitivity, and neutralizing antibody responses cross-reacted with early, late, and heterologous envelopes. The potential for broadly effective HIV-1 immunization is supported.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Serum-induced expression of the cdc25A gene by relief of E2F-mediated repression.

The cdc25A gene encodes a tyrosine phosphatase which activates cyclin-dependent kinase activity in the G1 phase of the cell cycle. cdc25A RNA levels are induced from 3 to 6 h after serum induction of serum-starved NIH 3T3 cells, suggesting that the cdc25A gene is a delayed-early gene. Analysis of cdc25A promoter constructs showed that the cdc25A promoter is sufficient for serum induction. Surprisingly for a gene expressed in early to mid-G1, serum induction of the promoter requires an E2F site at position -62 in the promoter. Deletion or point mutation of the E2F site resulted in activation of expression in serum-starved cells and no further induction by serum treatment. E2F factors were found to bind to the cdc25A E2F site along with the retinoblastoma protein (Rb) family members p130 and p107. A shift in mobility of the E2F-p107 complex in extracts of cells induced for 6 h correlated with induction of cdc25A expression. These results suggest that serum induction of cdc25A expression is mediated by inactivation of p107 or p130, both of which repress transcription when bound to the promoter through E2F.

3T3 Cells↗

PubMed1999

Higher cerebral function and hemispheric blood flow during awake carotid artery balloon test occlusions.

OBJECTIVES: Measures capable of detecting early alterations of brain function during acute cerebral ischaemia have not been adequately defined. Internal carotid artery (ICA) test occlusions provide a well controlled environment to investigate the effects of reversible acute hemispheric hypoperfusion on brain function. A continuous time estimation task was developed that reliably demonstrated alterations in higher cerebral function before development of any deficits in elementary neurological function during ICA balloon catheter test occlusions. In the present study, we hypothesised that alterations in our behavioural task would correlate significantly with absolute level of ipsilateral CBF. METHODS: Twenty five patients underwent awake ICA test occlusions during which sustained attention and ipsilateral CBF were measured simultaneously using our time estimation task and the intracarotid 133Xe washout method. Alteration in sustained attention was correlated with CBF after occlusion using Fisher's exact test. RESULTS: Deterioration in sustained attention was significantly associated with ipsilateral CBF below 30 ml/g/min (Fisher's exact test, p=0.047). Changes in individual patients' performance on the behavioural task correlated in real time with changes occurring either at the point of occlusion or at a specific threshold of induced hypotension. Sensitivity for our behavioural test in predicting CBF was 75%; specificity 70%. CONCLUSIONS: Monitoring sustained attention during carotid balloon test occlusions seems to be a sensitive means to detect decreases in CBF as measured by 133Xe washout. Correlation between higher cerebral function and CBF can allow more detailed investigations of physiological relations between cerebral haemodynamics and brain function in human conditions of cerebral ischaemia.

Adult↗

PubMed1999

Is acculturation a risk factor for early smoking initiation among Chinese American minors? A comparative perspective.

OBJECTIVE: To determine the extent to which Chinese American and white minors differ in age of smoking initiation, and to determine the effect of acculturation on smoking initiation. DESIGN: Cross-sectional telephone surveys. SETTING: Stratified random samples of the state of California, United States. SUBJECTS: 347 Chinese American and 10 129 white adolescents aged 12 through 17 years, from the California Tobacco Survey (1990-93) and the California Youth Tobacco Survey (1994-96). OUTCOME MEASURES: Hazards (risk) of smoking initiation by age, smoking initiation rate, cumulative smoking rate, mean age of smoking initiation, and acculturation status. STATISTICAL METHODS: Life table methods, proportional hazards models, and chi(2) tests. RESULTS: The risk of smoking initiation by age among Chinese American minors was about a third of that among white minors. The risk for Chinese Americans continued to rise even in later adolescence, in contrast to that for whites, which slowed after 15 years of age. Acculturation was associated significantly with smoking onset among Chinese Americans. Acculturation, smoking among social network members, attitudes toward smoking, and perceived benefits of smoking were associated with the difference in hazards of smoking onset between Chinese American minors and their white counterparts. CONCLUSIONS: Chinese American adolescents had a lower level and a different pattern of smoking onset than white adolescents. Levels of acculturation and other known risk factors were associated with the hazards of smoking initiation among Chinese American minors and with the difference in smoking initiation between the Chinese and white adolescents. Tobacco prevention policies, strategies, and programmes for ethnically diverse populations should take acculturation factors into account.

Acculturation↗

PubMed1999

Survival of insect pathogenic and human clinical isolates of Photorhabdus luminescens in previously sterile soil.

Most characterized strains of the bacterium Photorhabdus luminescens are symbionts of entomopathogenic nematodes, whereas other strains have been isolated from human clinical specimens. The ability of P. luminescens strains to survive and grow in soil has received limited attention, with some studies indicating these bacteria have little or no ability to persist in soil. Survival and (or) growth of P. luminescens strains in previously sterilized soil, and examination of different soil amendments on their numbers in soil, have not been previously reported. Entomopathogenic P. luminescens (ATCC 29999) and a human clinical isolate (ATCC 43949) were introduced into a soil that had been sterilized by autoclaving, with or without different soil amendments, and bacterial numbers were estimated over time by viable plate count. In the previously sterilized soil receiving no exogenous amendments, numbers fell drastically over a week's time, followed by an increase in numbers by day 30. Treatments involving the addition of calcium carbonate and gelatin or casamino acids to soil usually resulted in higher bacterial numbers. For some sampling dates and soil treatments, there were statistically significant differences between the numbers of the two bacterial strains recovered from soil. The two strains of P. luminescens used in this study were able to survive and grow after being inoculated into previously sterilized soil.

Amino Acids↗

PubMed1999

Suppression of PGE(2) fever at near term: reduced thermogenesis but not enhanced vasopressin antipyresis.

Fevers are known to be suppressed near term in the mother, but the mechanism responsible for this phenomenon is not understood. We tested the hypothesis that the suppression of fever at term is a result of enhanced vasopressin-induced antipyresis. Effects of intracerebroventricular prostaglandin E(2) (PGE(2)) were examined in rats at gestational days 16-17 and 19-20 (near term) and days 1-2 postpartum. PGE(2) (50 ng) elevated body and interscapular brown adipose tissue (iBAT) temperatures and increased sympathetic nerve activity to the iBAT. PGE(2)-induced changes in iBAT temperature and nerve activity, as well as in rectal temperature, were reduced or eliminated near term, and responses were recovered in the postpartum period. Blood pressure and heart rate changes induced by central PGE(2) were also decreased at near term. Coinfusion of Manning compound, a V(1) vasopressin receptor antagonist, with PGE(2) throughout the peripartum period did not reverse the suppressed iBAT temperature and nerve activity or body temperature responses to PGE(2). Microdialysis experiments revealed unchanged terminal release of vasopressin in the ventral septal area after PGE(2) infusion in either pregnant or parturient rats. These results suggest that fever reduction at near term is not associated with enhanced vasopressin antipyresis, but may be a result of reduced sympathetic tone and in particular a reduced sympathetic drive to the iBAT. This finding may reflect a generalized reduction in autonomic output around the time of parturition.

Adipose Tissue, Brown↗

PubMed1999

NOS inhibitor antagonism of PGE2-induced mechanical sensitization of cutaneous C-fiber nociceptors in the rat.

Prostaglandins, metabolites of arachidonic acid, released during tissue injury and inflammation sensitize primary afferent nociceptors. While it has been suggested that this effect on nociceptors is mediated mainly via the cAMP second messenger system, recent evidence suggests that nitric oxide (NO) is also involved in peripheral pain mechanisms. To test the hypothesis that NO contributes to the sensitization of nociceptors to mechanical stimuli induced by hyperalgesic prostaglandins, we compared von Frey hair mechanical threshold as well as the response evoked by 10-s sustained threshold mechanical stimulation before and after injection of prostaglandin E2 (PGE2) alone, and NOS inhibitor NG-methyl-L-arginine (L-NMA) or its inactive stereoisomer NG-methyl-D-arginine (D-NMA) plus PGE2, adjacent to the receptive field of C-fiber nociceptors. The reduction of mechanical threshold and increase in number of action potentials to sustained mechanical stimulation induced by intradermal application of PGE2 was blocked by L-NMA, but not D-NMA. It is suggested that NO contributes to nociceptor sensitization induced by hyperalgesic prostaglandins.

Animals↗

PubMed1999

Vasopressin and amastatin induce V(1)-receptor-mediated suppression of excitatory transmission in the rat parabrachial nucleus.

We examined actions of arginine vasopressin (AVP) and amastatin (an inhibitor of the aminopeptidase that cleaves AVP) on synaptic currents in slices of rat parabrachial nucleus using the nystatin-perforated patch recording technique. AVP reversibly decreased the amplitude of the evoked, glutamate-mediated, excitatory postsynaptic current (EPSC) with an increase in paired-pulse ratio. No apparent changes in postsynaptic membrane properties were revealed by ramp protocols, and the inward current induced by a brief application of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was unchanged after AVP. The reduction induced by 1 microM AVP could be blocked by a V(1) AVP receptor antagonist, [d(CH(2))(5)(1)-O-Me-Tyr(2)-Arg(8)]-vasopressin (Manning compound, 10 microM). Bath application of an aminopeptidase inhibitor, amastatin (10 microM), reduced the evoked EPSC, and AVP induced further synaptic depression in the presence of amastatin. Amastatin's effects also could be antagonized by the Manning compound. Corticotropin-releasing hormone slightly increased the EPSC at 1 microM, and coapplication with AVP attenuated the AVP response. Pretreatment of slices with 1 microg/ml cholera toxin or 0.5 microg/ml pertussis toxin for 20 h did not significantly affect AVP's synaptic action. The results suggest that AVP has suppressant effects on glutamatergic transmission by acting at V(1) AVP receptors, possibly through a presynaptic mechanism involving a pertussis-toxin- and cholera-toxin-resistant pathway.

2-Amino-5-phosphonovalerate↗

PubMed1999

Social readjustment and ischemic stroke: lack of an association in a multiethnic population.

Clinical experience has suggested that stressful life events and ongoing stressful illness, collectively termed 'social readjustment', may precipitate stroke. We investigated the association between a simple in-office evaluation of such stressors and stroke in an urban, multiethnic study population. Cases were patients from the Northern Manhattan Stroke Study with first ischemic stroke; controls were derived through random digit dialing with n:m matching for age, gender, and race-ethnicity. Social readjustment was measured through in-person interview using Amster and Krauss' Geriatric Social Readjustment Rating Scale (GSRRS), a one-time, 35-item, checklist type weighted questionnaire of stressful life events occurring in the previous 6 months. Conditional logistic regression was used to analyze the GSRRS and its quartiles as well as stressful events subgroups, adjusting for education, hypertension, cardiac disease, diabetes, and number of weekly visits as a measure of socialization. Six hundred and fifty-five cases of ischemic stroke and 1,087 controls were utilized. The mean age of the cases was 69.8 years, with 55.4% women, 51.0% Hispanics, 28.4% blacks, and 19.1% whites. GSRRS scores ranged from 0 to 812; the mean score was 205.5 for the cases and 206.2 for the controls. The analysis showed no association between stroke and a 20-point increase on the GSRRS (OR = 1.01, 95% CI = 0.99-1.01). There was also no effect for the second, third or highest versus lowest quartile. No association was found in age, gender or race-ethnic subgroups, or when analyzing negative events, severely threatening events, or ongoing stressful illnesses separately. While this study does not preclude social readjustment as a stroke risk factor, it suggests that the one-time assessment often done in the medical office setting has little relevance for stroke prevention planning.

Adult↗

PubMed1999

Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter.

Kidney proximal tubule cells take up Krebs cycle intermediates for metabolic purposes and for secretion of organic anions through dicarboxylate/organic anion exchange. Alteration in reabsorption of citrate is closely related to renal stone formation. The presence of distinct types of sodium-coupled dicarboxylate transporters has been postulated on either side of the polarized epithelial membrane in the kidney proximal tubule. Using a PCR-based approach, we isolated a novel member of the sodium-dependent dicarboxylate/sulfate transporter called SDCT2. SDCT2 is a 600-amino acid residue protein that has 47-48% amino acid identity to SDCT1 and NaDC-1, previously identified in kidney and intestine. Northern analysis gave a single band of 3.3 kb for SDCT2 in kidney, liver, and brain. In situ hybridization revealed that SDCT2 is prominently expressed in kidney proximal tubule S3 segments and in perivenous hepatocytes, consistent with the sites of high-affinity dicarboxylate transport identified based on vesicle studies. A signal was also detected in the meningeal layers of the brain. SDCT2 expressed in Xenopus oocytes mediated sodium-dependent transport of di- and tricarboxylates with substrate preference for succinate rather than citrate, but excluding monocarboxylates. SDCT2, unlike SDCT1, displayed a unique pH dependence for succinate transport (optimal pH 7.5-8.5) and showed a high affinity for dimethylsuccinate, two features characteristic of basolateral transport. These data help to interpret the mechanisms of renal citrate transport, their alteration in pathophysiological conditions, and their role in the elimination of organic anions and therapeutic drugs.

Amino Acid Sequence↗

PubMed1999

The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects.

We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing 2H20 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 microM at 16 hours to 43 microM at 20 hours, and then rebounded to 1,823 microM at 24 hours. GNG decreased from 58.1% at 16 hours to 38.6% of endogenous glucose production at 20 hours (P < 0.005) and then rebounded to 78. 9% at 24 hours (P < 0.05). Conversely, glycogenolysis (GL) increased from 41.9% at 16 hours to 61.4% at 20 hours (P < 0.05), and then decreased to 21.1% at 24 hours (P < 0.05). In the second study (controls; n = 6), volunteers were analyzed between 16 and 24 hours after the last meal. FFA rose from 423 to 681 microM (P < 0.05), and GNG from 50.3% to 61.7% (P < 0.02), whereas GL decreased from 49.7% to 38.3% (P < 0.05). Endogenous glucose production decreased at the same rate in both studies, from 10.7 to 8.6 micromol/kg/min (P < 0. 05). In study 3 (n = 6), in which the NA-mediated decrease of plasma FFA was prevented by infusion of lipid and heparin, neither FFA nor GNG changed significantly. In summary, our data suggest that (a) acute changes in plasma FFA produce acute changes in GNG and reciprocal changes in GL; (b) the decrease in EGP between 16 and 24 hours of fasting is due to a fall in GL; and (c) NA has no direct effect on GNG.

Adult↗

PubMed1999

Low levels of transthyretin in the CSF of depressed patients.

OBJECTIVE: Transthyretin plays an important role in the transport and distribution of thyroid hormone in the central nervous system (CNS). This study replicated and extended to patients with nonrefractory depressive illness a pilot study indicating that patients with refractory major depression have significantly lower levels of CSF transthyretin than do healthy comparison subjects. METHOD: Lumbar punctures were performed in drug-free subjects with DSM-III-R major depression (N = 18), DSM-III-R bipolar disorder, depressed phase (N = 1), and healthy comparison subjects (N = 24). CSF concentrations of transthyretin, determined by a quantitative dot-immunobinding assay, of the depressed patients and comparison subjects were compared by analysis of covariance (ANCOVA). The relationship between CSF transthyretin levels and Hamilton Depression Rating Scale scores was determined in a subset of the depressed patients. RESULTS: CSF concentrations of transthyretin were significantly lower in the depressed patients than in the comparison subjects by ANCOVA. Within the depressed group there was no significant overall correlation between CSF transthyretin levels and Hamilton depression scale scores, but there was a significant inverse correlation in male depressed patients (N = 8) between CSF transthyretin concentrations and Hamilton depression scores. CONCLUSIONS: Lower CSF transthyretin concentrations in depressed patients may reflect either a stable trait in this population or a state change secondary to depression or other factors. Lower CSF transthyretin concentrations may result in altered CNS thyroid hormone homeostasis. Such alteration could account for certain mood and neurovegetative symptoms of depression and might contribute to failure of standard antidepressant treatment.

Adult↗

PubMed1999

Neuraminidase inhibitors as anti-influenza virus agents.

Influenza virus neuraminidase (NA) catalyses the cleavage of sialic acid residues terminally linked to glycoproteins and glycolipids and plays an important role in the replication of the virus. Recently, several potent NA inhibitors have been synthesized based on the rational design of mimicking the transition state of the sialic acid cleavage. Zanamivir and oseltamivir (GS 4104, the prodrug of GS 4071) have emerged as promising influenza NA inhibitors for the treatment and prophylaxis of human influenza virus infection. This review describes the recent work toward the discovery and development of influenza NA inhibitors.

Animals↗

PubMed1999

Insulin inhibits angiotensinogen gene expression via the mitogen-activated protein kinase pathway in rat kidney proximal tubular cells.

The present study aimed to investigate the molecular mechanism(s) of insulin action on angiotensinogen (ANG) secretion and gene expression in kidney proximal tubular cells exposed to high levels of glucose. Immortalized rat proximal tubular cells (IRPTC) were cultured in monolayer. The levels of rat ANG and ANG messenger RNA in the IRPTC were quantified by a specific RIA for rat ANG (RIA-rANG) and by an RT-PCR assay. Insulin inhibited the stimulatory effect of a high level of glucose (25 mM) and phorbol 12-myristate 13-acetate, an activator of protein kinase C) on the secretion of ANG and the expression of the ANG messenger RNA in IRPTC. This inhibitory action of insulin on the ANG secretion and gene expression was blocked by PD98059 (an inhibitor of mitogen-activated protein kinase kinase) but not by Wortmannin (an inhibitor of phosphatidylinositol-3-kinase). PD98059 was effective in inhibiting the phosphorylation of MEK 1/2 and p44/42 MAP kinase in IRPTC stimulated by insulin. These studies demonstrate that insulin prevents the stimulatory effect of high levels of glucose on the expression of the renal ANG gene in IRPTC, at least in part, via the MAPK kinase signal transduction pathway, subsequently inhibiting the activation of the local renal renin-angiotensin system.

Androstadienes↗

PubMed1999

Disruption of circadian insulin secretion is associated with reduced glucose uptake in first-degree relatives of patients with type 2 diabetes.

The objective of this study was to evaluate whether first-degree relatives (FDRs) of patients with type 2 diabetes had abnormal circadian insulin secretion and, if so, whether this abnormality affected their glucose metabolism. Six African-American FDRs with normal glucose tolerance and 12 matched normal control subjects (who had no family history of diabetes) were exposed to 48 h of hyperglycemic clamping (approximately 12 mmol/l). Insulin secretion rates (ISRs) were determined by deconvolution of plasma C-peptide levels using individual C-peptide kinetic parameters. Detrending and smoothing of data (z-scores) and computation of autocorrelation functions were used to identify ISR cycles. During the initial hours after start of glucose infusions, ISRs were approximately 60% higher in FDRs than in control subjects (585 vs. 366 nmol/16 h, P < 0.05), while rates of glucose uptake were the same (5.6 mmol x kg(-1) x h(-1)), indicating that the FDRs were insulin resistant. Control subjects had well-defined circadian (24 h) cycles of ISR and plasma insulin that rose in the early morning, peaked in the afternoon, and declined during the night. In contrast, FDRs had several shorter ISR cycles of smaller amplitude that lacked true periodicity. This suggested that the lack of a normal circadian ISR increase had made it impossible for the FDRs to maintain their compensatory insulin hypersecretion beyond 18 h of hyperglycemia. As a result, ISR decreased to the level found in control subjects, and glucose uptake fell below the level of control subjects (61 vs. 117 micromol x kg(-1) x min(-1), P < 0.05). In summary, we found that FDRs with normal glucose tolerance had defects in insulin action and secretion. The newly recognized insulin secretory defect consisted of disruption of the normal circadian ISR cycle, which resulted in reduced insulin secretion (and glucose uptake) during the ascending part of the 24 h ISR cycle.

Adult↗

PubMed1999

Effects of fatty acids and ketone bodies on basal insulin secretion in type 2 diabetes.

The objective of this study was to assess the role of free fatty acids (FFAs) as insulin secretagogues in patients with type 2 diabetes. To this end, basal insulin secretion rates (ISR) in response to acute increases in plasma FFAs were evaluated in patients with type 2 diabetes and in age- and weight-matched nondiabetic control subjects during 1) intravenous infusion of lipid plus heparin (L/H), which stimulated intravascular lipolysis, and 2) the FFA rebound, which followed lowering of plasma FFAs with nicotinic acid (NA) and was a consequence of increased lipolysis from the subject's own adipose tissue. At comparable euglycemia, diabetic patients had similar ISR but higher plasma beta-hydroxybutyrate (beta-OHB) levels during L/H infusion and higher plasma FFA and beta-OHB levels during the FFA rebound than nondiabetic control subjects. Correlating ISR with plasma FFA plus beta-OHB levels showed that in response to the same changes in FFA plus beta-OHB levels, diabetic patients secreted approximately 30% less insulin than nondiabetic control subjects. In addition, twice as much insulin was secreted during L/H infusion as during the FFA rebound in response to the same FFA/beta-OHB stimulation by both diabetic patients and control subjects. Glycerol, which was present in the infused lipid (272 mmol/l) did not affect ISR. We concluded that 1) assessment of FFA effects on ISR requires consideration of effects on ISR by ketone bodies; 2) ISR responses to FFA/beta-OHB were defective in patients with type 2 diabetes (partial beta-cell lipid blindness), but this defect was compensated by elevated plasma levels of FFAs and ketone bodies; and 3) approximately two times more insulin was released per unit change in plasma FFA plus beta-OHB during L/H infusion than during the FFA rebound after NA. The reason for this remains to be explored.

3-Hydroxybutyric Acid↗

PubMed1999

Effect of insulin on fat metabolism during and after normal pregnancy.

Whereas development of resistance to the action of insulin on glucose metabolism during gestation has been recognized, it is presently not known whether there is also resistance to the action of insulin on lipid metabolism. We have, therefore, examined the effect of physiological hyperinsulinemia (during euglycemic-hyperinsulinemic clamping) on free fatty acid (FFA) turnover in seven nondiabetic overweight or obese women during and after pregnancy. Basal rates of FFA release, oxidation, and reesterification and basal plasma FFA concentrations were not significantly different from each other during the 2nd and 3rd trimester of pregnancy and postpartum. During euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamping, however, lipolysis was significantly less inhibited during the 3rd trimester (from 7.0 +/- 0.9 to 4.9 +/- 0.9 micromol x kg(-1) x min(-1), -30%) than during the 2nd trimester (from 8.4 +/- 0.6 to 4.1 +/- 0.9 micromol x kg(-1) x min(-1), -51%) and postpartum (from 8.5 +/- 1.1 to 4.2 +/- 0.6 micromol x kg(-1) x min(-1), -51%). Similarly, fat oxidation was not inhibited at all (from 3.5 +/- 0.3 to 3.8 +/- 0.5 micromol x kg(-1) x min(-1)) during the 3rd trimester but was suppressed by 51% (from 3.9 +/- 0.2 to 1.9 +/- 0.3 micromol x kg(-1) x min(-1)) during the 2nd trimester and by 38% (from 2.6 +/- 0.7 to 1.6 +/- 0.5 micromol x kg(-1) x min(-1) postpartum. These data demonstrated that resistance to the action of insulin on lipolysis and on fat oxidation developed during late gestation and disappeared postpartum.

Adult↗