Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins.
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Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins. (+info)
Effect of the glycemic index and content of indigestible carbohydrates of cereal-based breakfast meals on glucose tolerance at lunch in healthy subjects.
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BACKGROUND: Diets with a low glycemic index (GI) have been shown to improve glucose tolerance in both healthy and diabetic subjects. Two potential mechanisms are discussed in relation to long-term metabolic effects: a decreased demand for insulin in the postprandial phase and formation of short-chain fatty acids from fermentation of indigestible carbohydrates in the colon. OBJECTIVE: The objective was to study the effect of the GI and the indigestible carbohydrate--resistant starch (RS) and dietary fiber (DF)--content of cereal-based breakfasts on glucose tolerance at a second meal (lunch) in healthy subjects. DESIGN: The effects of 7 test breakfasts with known GIs (GI: 52-99) and RS + DF contents (2-36 g) were evaluated. White-wheat bread was used as a reference breakfast (high GI, low RS + DF content). Glucose and insulin responses after the second meal were measured in healthy subjects. In addition, the satiating capacity of 4 of the 7 test breakfasts was estimated before and during the second meal. RESULTS: Two of the 4 low-GI breakfasts improved glucose tolerance at the second meal. Only these 2 breakfasts were capable of postponing the in-between-meal fasting state. There was no measurable effect of fermentable carbohydrates on glucose tolerance at the second meal. The highest satiety score was associated with the barley breakfast that had a low GI and a high RS + DF content. CONCLUSIONS: Glucose tolerance can improve in a single day. Slow absorption and digestion of starch from the breakfast meal, but not the content of indigestible carbohydrates in the breakfast meal, improved glucose tolerance at the second meal (lunch). (+info)
Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa.
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BACKGROUND: Vitamin A supplementation is being used successfully to treat some forms of cancer and the degenerative eye disease retinitis pigmentosa. The daily biological need for vitamin A is estimated to be 800 retinol equivalents (RE)/d (2667 IU/d) for adult women and 1000 RE/d (3300 IU/d) for adult men; doses > or = 7500 RE (> or = 25000 IU)/d are considered potentially toxic over the long term. OBJECTIVE: We assessed the safety in adults of long-term vitamin A supplementation with doses above the daily biological need but <7500 RE (<25000 IU)/d. DESIGN: Adults aged 18-54 y with retinitis pigmentosa but in generally good health (n = 146) were supplemented with 4500 RE (15000 IU) vitamin A/d for < or = 12 y (group A) and compared with a similar group (n = 149) that received 23 RE (75 IU)/d (trace group). Mean total consumption of vitamin A in group A was 5583 RE (18609 IU)/d (range: 4911-7296 RE/d, or 16369-24318 IU/d) and that in the trace group was 1053 RE (3511 IU)/d (range: 401-3192 RE/d, or 1338-10638 IU/d). RESULTS: Patients in group A showed an 8% increase in mean serum retinol concentration at 5 y and an 18% increase at 12 y (P < 0.001); no retinol value exceeded the upper normal limit (3.49 micromol/L, or 100 microg/dL). Mean serum retinyl esters were elevated approximately 1.7-fold at 5 y and remained relatively stable thereafter. No clinical symptoms or signs of liver toxicity attributable to vitamin A excess were detected. CONCLUSIONS: Prolonged daily consumption of <7500 RE (<25000 IU) vitamin A/d can be considered safe in this age group. (+info)
Many LH peaks are needed to physiologically stimulate testosterone secretion: modulation by fasting and NPY.
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The pulsatile luteinizing hormone (LH) and testosterone secretions were studied during serial blood collections performed at 7-min time intervals in the male rat. In fed rats, a discontinuous pattern of LH secretion was observed. Periods without secretion alternated with active secretory episodes consisting in trains of three to four LH peaks that triggered testosterone secretion usually 1-2 h later. The magnitude of the testosterone response was not correlated with the amplitude of the LH peaks. Isolated, single peaks of LH did not evoke clear testosterone responses. Forty-eight hours after initiation of fasting, testosterone secretion was markedly decreased, but integrated LH secretion was only partly reduced. Chronic infusion of neuropeptide Y (NPY; 18 microgram/day, icv) reduced testosterone secretion to very low levels and abolished pulsatile LH secretion or testosterone response to isolated LH peaks. In conclusion, the stimulation of testosterone secretion by LH necessitates several LH peaks organized in a proper sequence, and the testosterone response is not immediate. Low testosterone secretion in fasting rats appears to result from disappearance of coordinated, multiple LH peaks of sufficient size. Inhibition of the gonadotropic axis achieved by central NPY administration is due to either absence of LH peak "clusters" or occurrence of nonfunctional single LH peaks. (+info)
Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis.
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Circulating leptin concentrations are raised in animal models of inflammation and sepsis. The purpose of this study was to determine the effect of sepsis on serum leptin concentration in humans and to examine the relationship between leptin and the metabolic consequences of sepsis. Resting energy expenditure, insulin sensitivity, and fasting serum leptin, plasma insulin, and cortisol concentrations were measured in 20 subjects with intra-abdominal sepsis and 20 healthy control subjects, before and during a 2-h period of euglycemic hyperinsulinemia. Fasting serum leptin concentrations were similar in septic and control subjects. In simple regression analysis, serum leptin concentrations correlated significantly with percent body fat in both septic patients (r = 0. 64, P < 0.005) and healthy subjects (r = 0.75, P < 0.0001). Multiple regression analyses additionally indicated that percent body fat, fasting plasma insulin, and plasma cortisol, but not sepsis, were significant and independent determinants of serum leptin concentration. No relationship between leptin and resting energy expenditure or insulin sensitivity was identifiable. A major metabolic role for leptin in human sepsis therefore appears unlikely. (+info)
Carbohydrate ingestion can completely suppress endogenous glucose production during exercise.
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The purposes of this study were 1) to investigate the effect of carbohydrate (CHO) ingestion on endogenous glucose production (EGP) during prolonged exercise, 2) to study whether glucose appearance in the circulation could be a limiting factor for exogenous CHO oxidation, and 3) to investigate whether large CHO feedings can reduce muscle glycogen oxidation during exercise. Six well-trained subjects exercised three times for 120 min at 50% maximum workload while ingesting water (FAST), a 4% glucose solution (LO-Glc), or a 22% glucose solution (HI-Glc). A primed continuous intravenous [6, 6-2H2]glucose infusion was given, and the ingested glucose was enriched with [U-13C]glucose. Glucose ingestion significantly elevated CHO oxidation as well as the rates of appearance (Ra) and disappearance. Ra glucose equaled Ra of glucose in gut (Ra gut) during HI-Glc, whereas EGP was completely suppressed. During LO-Glc, EGP was partially suppressed, whereas Ra gut provided most of the total glucose Ra. We conclude that 1) high rates of CHO ingestion can completely block EGP, 2) Ra gut may be a limiting factor for exogenous CHO oxidation, and 3) muscle glycogen oxidation was not reduced by large glucose feedings. (+info)
Effect of a selective rise in hepatic artery insulin on hepatic glucose production in the conscious dog.
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In the present study we compared the hepatic effects of a selective increase in hepatic sinusoidal insulin brought about by insulin infusion into the hepatic artery with those resulting from insulin infusion into the portal vein. A pancreatic clamp was used to control the endocrine pancreas in conscious overnight-fasted dogs. In the control period, insulin was infused via peripheral vein and the portal vein. After the 40-min basal period, there was a 180-min test period during which the peripheral insulin infusion was stopped and an additional 1.2 pmol. kg-1. min-1 of insulin was infused into the hepatic artery (HART, n = 5) or the portal vein (PORT, n = 5, data published previously). In the HART group, the calculated hepatic sinusoidal insulin level increased from 99 +/- 20 (basal) to 165 +/- 21 pmol/l (last 30 min). The calculated hepatic artery insulin concentration rose from 50 +/- 8 (basal) to 289 +/- 19 pmol/l (last 30 min). However, the overall arterial (50 +/- 8 pmol/l) and portal vein insulin levels (118 +/- 24 pmol/l) did not change over the course of the experiment. In the PORT group, the calculated hepatic sinusoidal insulin level increased from 94 +/- 30 (basal) to 156 +/- 33 pmol/l (last 30 min). The portal insulin rose from 108 +/- 42 (basal) to 192 +/- 42 pmol/l (last 30 min), whereas the overall arterial insulin (54 +/- 6 pmol/l) was unaltered during the study. In both groups hepatic sinusoidal glucagon levels remained unchanged, and euglycemia was maintained by peripheral glucose infusion. In the HART group, net hepatic glucose output (NHGO) was suppressed from 9.6 +/- 2.1 micromol. kg-1. min-1 (basal) to 4.6 +/- 1.0 micromol. kg-1. min-1 (15 min) and eventually fell to 3.5 +/- 0.8 micromol. kg-1. min-1 (last 30 min, P < 0.05). In the PORT group, NHGO dropped quickly (P < 0.05) from 10.0 +/- 0.9 (basal) to 7.8 +/- 1.6 (15 min) and eventually reached 3.1 +/- 1.1 micromol. kg-1. min-1 (last 30 min). Thus NHGO decreases in response to a selective increase in hepatic sinusoidal insulin, regardless of whether it comes about because of hyperinsulinemia in the hepatic artery or portal vein. (+info)
Reduced glucose availability attenuates circadian responses to light in mice.
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To test whether circadian responses to light are modulated by decreased glucose availability, we analyzed photic phase resetting of the circadian rhythm of locomotor activity in mice exposed to four metabolic challenges: 1) blockade of glucose utilization induced by 2-deoxy-D-glucose (2-DG), 2) fasting (food was removed for 30 h), 3) insulin administration, and 4) insulin treatment after fasting. In mice housed in constant darkness, light pulses applied during early subjective night induced phase delays of the rhythm of locomotor activity, whereas light pulses applied during late subjective night caused phase advances. There was an overall reduction of light-induced phase shifts, with a more pronounced effect for delays, in mice pretreated with 500 mg/kg ip 2-DG compared with mice injected with saline. Administration of glucose with 2-DG prevented the reduction of light-induced phase delays. Furthermore, phase delays were reduced in fed mice pretreated with 5 IU/kg sc insulin and in fasted mice injected with saline or insulin compared with control fed mice. These results show that circadian responses to light are reduced when brain glucose availability is decreased, suggesting a metabolic modulation of light-induced phase shifts. (+info)