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Biomedical subjects

R H Eckel

Publications and source records attributed to R H Eckel.

At least 91 records · Page 5Linked to original sources
PubMed1992

Preheparin lipoprotein lipolytic activities: relationship to plasma lipoproteins and postheparin lipolytic activities.

To determine the putative metabolic relevance of preheparin versus postheparin lipoprotein lipases, the relationships of both pre- and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) to plasma triglycerides, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol were determined in 93 men. Relationships of preheparin lipases to their respective postheparin lipases were also examined. Although relationships between the preheparin lipases and plasma triglycerides and HDL cholesterol were not apparent, both preheparin LPL (rs = 0.306, P = 0.0036) and HTGL (rs = 0.348, P = 0.0008) correlated with LDL cholesterol, a relationship not seen with either postheparin lipase. Both postheparin LPL (rs = 0.515, P = 0.0001) and postheparin HTGL (rs = -0.228, P = 0.0028), however, correlated with HDL cholesterol. In addition, postheparin LPL was inversely correlated with postheparin HTGL (rs = -0.363, P = 0.0003), whereas the relationship between preheparin LPL and preheparin HTGL was positive (rs = 0.228, P = 0.0009). Overall, these data point to differences between pre- and postheparin lipases in their relationships to lipoproteins, and one to another. The relationships of LDL cholesterol to both preheparin LPL and HTGL suggest that displacement of active forms of both lipases from their endothelial binding sites may mark triglyceride-rich lipoproteins or their remnants for metabolic pathways that lead to LDL.

Adult↗
PubMed1991

Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans.

Eight normal-weight subjects (four men, four women) were studied to determine the relative activities of lipoprotein lipase (LPL) in adipose tissue (ATLPL) and vastus lateralis skeletal muscle (SMLPL), both in the fasting state and in response to a 6-hour insulin/glucose infusion. Mean fasting levels of ATLPL and SMLPL were not statistically different. After 6 hours of insulin/glucose infusion, mean ATLPL activity was significantly greater than the fasting level (P less than .01), while mean SMLPL activity decreased from basal (P less than .05). These tissue-specific changes in LPL responsiveness (0 to 6 hours) were significantly different (P less than .01). No differences between men and women were observed. These divergent tissue-specific LPL responses to insulin/glucose would serve to direct lipoprotein triglyceride-derived fatty acids away from muscle and to adipose tissue for storage.

Adipose Tissue↗
PubMed1991

Weight reduction increases adipose but decreases cardiac LPL in reduced-obese Zucker rats.

Lipoprotein lipase (LPL) activity and mRNA levels were measured in cardiac muscle and adipose tissue from lean, obese, and weight-stable reduced-obese Zucker rats, both fasted and 2 h after feeding. Fasting epididymal fat LPL activity was substantially higher in obese rats relative to lean rats [6.9 vs. 0.2 nmol free fatty acid (FFA).10(6) cells-1.min-1; P = 0.0001], and was higher still in reduced-obese rats (15.7 nmol FFA.10(6) cells-1.min-1; P = 0.002). Adipose tissue LPL increased with feeding in all three groups. In marked contrast, fasting cardiac muscle LPL was lower in obese rats relative to lean (28.8 vs. 38.5 nmol FFA.g-1.min-1; P = 0.0064) and was lower still in reduced-obese rats (14.5 nmol FFA.g-1.min-1; P = 0.0001). LPL mRNA levels increased in adipose tissue along with enzyme activity; however, the magnitude of the changes were relatively small, suggesting that the primary regulatory steps are posttranslational. Weight reduction studies were also carried out in Sprague-Dawley rats with similar results. These studies show that sustained weight reduction results in coordinate changes in tissue-specific LPL, favoring delivery of lipoprotein triglyceride fatty acids to adipose tissue relative to cardiac muscle and the restoration of energy stores.

Adipose Tissue↗
PubMed1991

Relationship between habitual physical activity and insulin levels among nondiabetic men and women. San Luis Valley Diabetes Study.

OBJECTIVE: To determine whether higher levels of physical activity would be associated with lower fasting insulin and C-peptide levels in a free-living nondiabetic population. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted with a Hispanic and non-Hispanic white population of 442 men and 489 women with normal glucose tolerance (by World Health Organization criteria) in two rural Colorado counties. Total physical activity was assessed by a 7-day physical activity recall from which metabolic equivalents were estimated. Relationships between metabolic equivalents and fasting insulin and C-peptide were assessed while considering obesity, age, and other risk factors known to influence fasting insulin levels. RESULTS: Among all subjects, univariate analyses showed that higher activity levels were associated with lower mean fasting insulin and C-peptide levels (P less than or equal to 0.05). Multiple linear regression showed that higher activity was significantly associated with lower values of log fasting insulin and C-peptide levels in men only (P less than 0.001) independent of obesity, fat distribution, and age. Men in the highest tertile of activity had an adjusted mean fasting insulin level of 59.2 pM and fasting C-peptide level of 0.5 nM compared with a fasting insulin level of 72.7 pM and fasting C-peptide level of 0.6 mM for men in the lowest tertile of activity. The magnitude of the inverse association between activity and insulin was greatest in older rather than younger men. Physical activity was not associated with fasting insulin or C-peptide levels in women in the multivariate analyses. CONCLUSIONS: Based on cross-sectional data, we conclude that higher levels of habitual physical activity are associated with lower fasting insulin and C-peptide levels in Hispanic and non-Hispanic white men.

Adult↗
PubMed1991

Levels of acylation stimulating protein in obese women before and after moderate weight loss.

Acylation stimulating protein (ASP) is a small (MW 14,000) basic (pI 9.0) protein which has only recently been purified from human plasma. Since ASP is the most potent known stimulant of triglyceride synthesis in human adipose tissue, the present study was designed to determine if plasma ASP was elevated in patients with moderate obesity, and if so, whether this level changed with weight loss. Fasting plasma ASP levels were determined by competitive ELISA immunoassay in 10 obese women before weight loss, immediately after weight loss, and 3 months after maintaining weight reduction. Their plasma ASP results were compared to 17 age and sex-matched lean controls. With weight loss, plasma ASP decreased significantly: 19.6 +/- 10.7 mg/dl before weight loss vs 15.0 +/- 9.5 mg/dl after weight loss vs 13.8 +/- 7.7 mg/dl 3 months after being weight stable, P less than 0.05 initial vs final value. Nevertheless, plasma ASP was significantly higher than the control value at all three times. Thus, before weight loss, the average ASP in the obese group was four times that in the control group (19.6 +/- 10.7 vs 5.1 +/- 3.6 mg/dl, P less than 0.0005) while even 3 months after weight loss, it remained almost three times above the control group (13.8 +/- 7.7 vs 5.1 +/- 3.6 mg/dl, P less than 0.0005). The data suggest, therefore, that an elevated plasma level of ASP is common in obesity, that the level of plasma ASP may reflect the fat cell mass present in an individual, and raises the possibilities that ASP may play a role in initiation or maintenance of the obese state.

Adult↗
PubMed1991

Lipoprotein lipase in human milk: compartmentalization and effect of fasting, insulin, and glucose.

The object of this study was to investigate the effect of maternal metabolic state on the activity of lipoprotein lipase (LPL) in human milk. Although the total LPL activity in milk was not significantly affected by up to three cycles of freezing and thawing, the amount of LPL associated with the cream fraction of the milk increased from an average of less than 10% to about 70% after this treatment. The enzyme was relatively stable when the milk was stored on ice, losing activity at a rate of about 1% per hour. At 37 degrees C degradation was more rapid, about 7% per hour. When LPL activity was measured in samples taken at hourly intervals by breast pump, using oxytocin to achieve a complete letdown at each pumping, activity was found to double from the first to the third pumping. Thereafter the activity was stable under fasting conditions. Hyperglycemic and euglycemic, hyperinsulinemic glucose clamp protocols were used to evaluate the effects of glucose and insulin. Both high plasma glucose and high plasma insulin in the presence of normal glucose significantly increased LPL activity within 4 hours. We conclude that, like adipose, tissue LPL, mammary LPL is regulated by plasma insulin.

Adult↗
PubMed1991

Distribution and source of lipoprotein lipase in mouse mammary gland.

During lactation lipoprotein lipase (LPL) is elevated in mammary tissue and depressed in adipose tissue to redirect lipids for incorporation into milk fat. The cellular origin of lipoprotein lipase in mammary tissue is thought to be the mammary epithelial cell which is the predominant cell type noticeable in the lactating gland; however, mammary adipocytes are also present. If lipoprotein lipase is produced by adipocytes in other sites of the body, then the question remains as to why mammary adipocytes have not been shown to produce lipoprotein lipase. In this study we present several lines of evidence that indicate that the mammary adipocyte is a source of LPL in the lactating mammary gland of mice. This evidence includes the absence of extracellular and intracellular lipoprotein lipase activity in two types of primary mammary epithelial cell cultures and a similarity in the changes of lipoprotein lipase activity in genital adipose tissue from nonpregnant mice and lactating mammary tissue to the nutritional state of the animal. Other evidence presented here includes strong localization of lipoprotein lipase protein and messenger RNA by fluorescence immunohistochemistry and in situ hybridization, respectively, to interstitial cells located between epithelial structures. We postulate that these interstitial cells are regressed, lipid-deleted mammary adipocytes.

Adipose Tissue↗
PubMed1990

Urinary organic acid excretion during feeding of medium-chain or long-chain triglyceride diets in patients with non-insulin-dependent diabetes mellitus.

Medium-chain triglycerides (MCTs) are absorbed and metabolized differently from long-chain triglycerides (LCTs). Recent data indicate that MCTs may be useful as a dietary substitute in a variety of clinical disorders. The current studies were undertaken to characterize urinary organic acid excretion in patients with non-insulin-dependent diabetes mellitus during 4 d of an LCT or MCT diet. Urinary excretion of the dicarboxylic acids adipic, suberic, and 3-hydroxysebacic and the (omega-1) hydroxylation products 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, was increased during MCT feeding as compared with LCT feeding. Urinary suberic and 7-hydroxyoctanoic acid excretions were increased 55- and 30-fold, respectively, during the MCT-substituted diet. Urinary organic acid profiles provide information on the fate of lipids during MCT feeding and may also be useful in assessing complicance during clinical trials employing MCT-substituted diets.

Caproates↗
PubMed1990

Lipoprotein lipase gene expression in rat adipocytes is regulated by isoproterenol and insulin through different mechanisms.

Lipoprotein lipase (LPL) is highly regulated by catecholamines and insulin in adipocytes. Isoproterenol, a beta-adrenergic agonist, decreases LPL enzyme activity, whereas insulin increases LPL activity. We have isolated an 868-basepair rat LPL cDNA clone to assess hormone-mediated changes in LPL steady state mRNA levels and LPL gene transcription rates in adipocytes. Northern blot analysis of isoproterenol-treated (10(-6) M) adipocytes showed that LPL steady state mRNA decreased by 15 min. Nuclear run-on transcription assays in isoproterenol-treated cells indicated that LPL gene transcription was also decreased at 15 min compared to that in control cells. Conversely, insulin (6.7 x 10(-8) M) mediated an increase in LPL steady state mRNA in treated adipocytes, yet LPL gene transcription was not different from that in control cells. Thus, the isoproterenol-mediated decrease in LPL enzyme activity and steady state mRNA levels in adipocytes is associated with decreases in LPL gene transcription. Insulin, which does not affect LPL gene transcription, increases LPL enzyme activity and steady state mRNA levels. The effect of insulin on LPL mRNA is probably due to insulin-induced changes in mRNA stability.

Adipose Tissue↗
PubMed1989

Dextran sulfate is poorly absorbed after oral administration.

STUDY OBJECTIVE: To determine whether dextran sulfate (molecular weight, 7000 to 8000 daltons; 17% to 20% sulfur), a synthetic heparin analogue with anti-human immunodeficiency virus (HIV) activity in vitro, is absorbed after oral administration. DESIGN: Open-label, single-center study in two parts. The first part was a bioavailability study in which six subjects received a single 1800-mg oral dose and a single 225- or 300-mg intravenous dose. The second part was a study of the dose-response relation between dextran sulfate and total plasma lipolytic activity in which twelve subjects were given a single infusion of either 0.05, 0.5, 5, or 50 mg of dextran sulfate. SUBJECTS: Eighteen healthy volunteers. MEASUREMENTS AND MAIN RESULTS: In the bioavailability study, plasma and urine dextran-sulfate concentrations were measured by a competitive binding assay after each dose. In addition, two bioassays were used to assess plasma concentrations: plasma lipolytic activity and activated partial thromboplastin time (APTT). After the oral dose, plasma concentrations were not measurable with the competitive binding assay (lower limit of sensitivity, 1 microgram/mL); less than 0.5% of the dose was recovered in the urine, the APTT did not increase, and the median increase in the plasma lipolytic activity was only twofold (maximum increase, 11-fold). In contrast, after the intravenous dose of 225 mg, peak plasma concentrations by competitive binding assay were 26 to 35 micrograms/mL (median, 28 micrograms/mL); 25% to 29% (median, 25%) of the dose was recovered in the urine; the APTT increased to 3.5 to 9.2 times the baseline value (median increase, 6.9 times), and the plasma lipolytic activity increased by 185 to 548 times the baseline value (median increase, 438 times). In the dose-response study, intravenous doses as low as 0.5 mg produced significant increases in the plasma lipolytic activity. There was a steep dose-response curve between 0.5 and 50 mg. CONCLUSION: Dextran sulfate is very poorly absorbed after oral administration.

Administration, Oral↗
PubMed1989

Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases.

Lipoprotein lipase is an important regulator of lipid and lipoprotein metabolism. It also contributes to the lipid and energy metabolism of different tissues in varying ways. Although the synthesis, manner of secretion, and mechanism of endothelial binding of lipoprotein lipase appear similar in all tissues, the factors that control gene expression and posttranslational events related to processing vary from tissue to tissue. The actual molecular events that determine this tissue specificity are not yet understood. In the future, however, it may be possible to stimulate or inhibit the activity of lipoprotein lipase in specific tissues and to alter metabolic processes so as to improve the quality and length of life in patients with metabolic diseases such as hypertriglyceridemia, HDL2 deficiency, and obesity.

Humans↗
PubMed1989

Hypocaloric feeding in obese women: metabolic effects of medium-chain triglyceride substitution.

Medium-chain (MCT) and long-chain (LCT) triglyceride diets were compared during and after 4 or 12 wk of hypocaloric feeding in obese women to determine the effects on weight loss, ketones, nitrogen balance, and insulin action. After a base-line euglycemic clamp, two groups ingested an 800-kcal/d liquid diet with 30% of calories as LCT (group 1) or 6% of calories as LCT and 24% as MCT (group 2). Rate and amount of weight loss, serum ketones, and N balance were not different between groups. However, the subjects in group 2 (MCT) demonstrated an increase in glucose requirement to maintain euglycemia during the clamp after weight loss (delta 0.18 +/- 0.13 mmol.m-2.min-1) whereas subjects in group 1 (LCT) had a diminished requirement (delta -0.12 +/- 0.10, p = 0.036). Thus, an 800-kcal diet containing 24% of calories as MCT is safe and enhances insulin action but fails to increase the rate or amount of weight loss.

Adult↗
PubMed1989

HDL subfractions and adipose tissue metabolism in the reduced-obese state.

The effect of weight reduction on fasting serum lipids and lipoproteins and adipose tissue lipoprotein lipase responsiveness to insulin was assessed immediately after and 3 mo subsequent to a mean 11.7% weight reduction in 14 women. Whereas reduction in fasting serum triglycerides persisted after 3 mo, reductions in serum cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein (HDL) cholesterol were not found at 3 mo. In fact, at 3 mo, levels of HDL cholesterol were higher than before weight reduction. Maintenance of the reduced-obese state also increased the HDL2-to-HDL3 cholesterol ratio (P less than 0.01), an effect strongly associated with the change in the responsiveness of adipose tissue lipoprotein lipase to insulin (r = 0.821, P less than 0.001). Moreover, after maintenance of the reduced-obese state, the HDL2-to-HDL3 cholesterol ratio also increased after the ingestion of corn oil and a 6-h insulin-glucose infusion, a response not present before weight reduction. Thus the effect of weight reduction on serum lipids and lipoproteins was not only time dependent, but for HDL, was strongly associated with changes in adipose tissue metabolism.

Adipose Tissue↗
PubMed1989

Insulinlike growth factor action and production in adipocytes and endothelial cells from human adipose tissue.

Primary cultures of microvascular endothelial cells and isolated adipocytes were prepared from human omental adipose tissue to study the potentially overlapping roles of insulin and insulinlike growth factors (IGFs) in human adipose tissue. To determine whether adipocytes contain type I IGF receptors, binding experiments were carried out with 125I-labeled IGF-I. At 16 degrees C, saturation of specific binding to adipocytes was reached after 30 min and was 0.7% per 10(6) cells. At 37 degrees C, chloroquine produced an increase in cell-associated 125I-IGF-I, suggesting that IGF-I is internalized and degraded in a manner analogous to insulin. In competition experiments, IGF-I competed for binding more effectively than rat IGF-II or insulin. The concentrations of IGF-I, rat IGF-II, and insulin necessary to displace 50% of 125I-IGF-I binding were 2.5, 15, and 90 nM, respectively. In addition, a monoclonal antibody (alpha-IR3) that has been shown to block the type I IGF receptor was used in competition binding experiments. The antibody also inhibited binding of 125I-IGF-I to adipocytes. The biological effects of insulin and IGF-I were examined by studying adipocyte lipoprotein lipase (LPL). Insulin stimulated [14C]glucose incorporation into cellular lipid in a dose-dependent manner, with 50% effective concentration (EC50) of 0.3 nM. However, an increase in LPL activity was observed only at a high insulin concentration, with an EC50 of approximately 30 nM. In contrast, IGF-I stimulated a progressive increase in LPL, with an EC50 of 3.2 nM. In addition, alpha-IR3 blocked the stimulatory effect of IGF-I on adipocyte LPL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1989

Massive insulin overdose: detailed studies of free insulin levels and glucose requirements.

The course of a diabetic patient who self-administered 2500 U of NPH insulin subcutaneously was examined in detail. Despite resumption of oral intake on day 3, she required iv glucose for 6 days, during which time serum free insulin levels remained elevated. Glucose requirements closely matched those calculated from published euglycemic clamp data on maximal glucose disposal rates during insulin infusion. We postulate that her prolonged course was due to delayed absorption of the subcutaneous insulin. This is the first case of massive insulin overdose studied in such detail, and the results may facilitate management of future cases.

Adult↗
PubMed1988

Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia.

Insulin- and glyburide-stimulated changes in cytosolic free calcium concentrations [( Ca2+]i) were studied in gluteal adipocytes obtained from six obese women (139 +/- 3% ideal body wt) and six healthy, normal weight age- and sex-matched controls. Biopsies were performed after an overnight fast and twice (at 3 and 6 h) during an insulin infusion (40 mU/m2 per min) (euglycemic clamp). In adipocytes obtained from normal subjects before insulin infusion, insulin (10 ng/ml) increased [Ca2+]i from 146 +/- 26 nM to 391 +/- 66 nM. Similar increases were evoked by 2 microM glyburide (329 +/- 41 nM). After 3 h of insulin infusion, basal [Ca2+]i rose to 234 +/- 21 nM, but the responses to insulin and glyburide were completely abolished. In vitro insulin-stimulated 2-deoxyglucose uptake was reduced by insulin and glucose infusion (25% stimulation before infusion, 5.4% at 3 h, and 0.85% at 6 h of infusion). In obese patients, basal adipocyte [Ca2+]i was increased (203 +/- 14 nM, P less than 0.05 vs. normals). The [Ca2+]i response demonstrated resistance to insulin (230 +/- 23 nM) and glyburide (249 +/- 19 nM) stimulation. Continuous insulin infusion increased basal [Ca2+]i (244 +/- 24 nM) and there was no response to either insulin or glyburide at 3 and 6 h of study. Rat adipocytes were preincubated with 1-10 mM glucose and 10 ng/ml insulin for 24 h. Measurements of 2-deoxyglucose uptake demonstrated insulin resistance in these cells. Under these experimental conditions, increased levels of [Ca2+]i that were no longer responsive to insulin were demonstrated. Verapamil in the preincubation medium prevented the development of insulin resistance.

Adipose Tissue↗
PubMed1988

Fat calories may be preferentially stored in reduced-obese women: a permissive pathway for resumption of the obese state.

We previously demonstrated in unpaired studies that corn oil ingestion at the beginning of a euglycemic insulin clamp study decreased the responsiveness of gluteal adipose tissue lipoprotein lipase (ATLPL) to glucose/insulin in lean subjects. In this investigation, we performed paired euglycemic insulin clamp studies with glucose/insulin with or without oral corn oil in each of six lean [mean, 64 +/- 3 (+/- SE) kg] normal women and nine moderately obese (91 +/- 3 kg) women before and after 12.4 +/- 1.4-kg weight loss and 3 months of weight maintenance to determine if the inhibitory effect of fat calories existed in each of these states. In the obese women the fasting ATLPL activity [5.6 +/- 1.1 (+/- SE) neq FFA/10(6) cells.min] was greater than in the normal women (1.6 +/- 0.2) and did not change after weight loss and maintenance (5.0 +/- 0.7). As expected, in normal women corn oil ingestion diminished the responsiveness of ATLPL to glucose/insulin [change (delta), 0.2 +/- 0.2 vs. 3.3 +/- 0.8; P less than 0.02] during a 6-h euglycemic insulin (40 mU/m2.min) clamp. In obese women ATLPL activity did not change under either experimental condition (glucose/insulin with or without corn oil). However, after weight reduction ATLPL activity increased not only in response to glucose/insulin alone (delta, 7.7 +/- 2.4), but also in response to glucose/insulin when corn oil was ingested (delta, 7.9 +/- 2.8). Moreover, the response of ATLPL activity to glucose/insulin and corn oil was greater than that in lean women (P less than 0.05). Thus, in reduced-obese women not only did fasting ATLPL activity remain elevated and ATLPL responsiveness to glucose/insulin increase, but fat ingestion failed to blunt the ATLPL response. This inability of dietary fat to diminish the responsiveness of ATLPL to glucose/insulin and, therefore, the effect of the lipase on triglyceride deposition in adipose tissue could contribute to the resumption of the obese state that so commonly occurs after successful weight reduction.

Adipose Tissue↗