共查询到20条相似文献,搜索用时 15 毫秒
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R. SARACCI 《Journal of internal medicine》1993,233(1):41-43
Abstract. Prospective studies on diet and cancer are needed for five reasons: (i) unlike xenobiotic agents which, if found to be carcinogenic, can at least in principle be dispensed with, food of some kind is indispensable; (ii) our present knowledge on the role of diet in cancer is limited and permits only tentative recommendations; (iii) plausible biological hypotheses for this role are available, as well as biological markers allowing their exploration in epidemiological studies; (iv) these studies demand a prospective approach—a number of prospective studies, each involving several tens of thousands of adults, are now being started in Europe: and (v) diet affects not only cancers but also a spectrum of other diseases, which need to be investigated in parallel, to acquire knowledge on which to base firm recommendations on a diet capable of maximizing benefits and minimizing the risk to health. 相似文献
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Winnick JJ Sherman WM Habash DL Stout MB Failla ML Belury MA Schuster DP 《The Journal of clinical endocrinology and metabolism》2008,93(3):771-778
CONTEXT: Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus; however, the contributions of peripheral and hepatic tissues to these improvements are not known. OBJECTIVE: Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions. DESIGN: Subjects were randomly assigned to one of two groups. The energy balance group consumed an isocaloric diet consisting of 50% carbohydrate, 30% fat, and 20% protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70% of maximum oxygen consumption maximum during the second 7 d of the 15-d study period. Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study. SETTING: The study was performed at Ohio State University's General Clinical Research Center. PARTICIPANTS: There were 18 obese, mildly diabetic humans included in the study. INTERVENTION: Aerobic exercise training was performed for 7 d. MAIN OUTCOME MEASURES: Whole-body, peripheral, and hepatic insulin sensitivity were measured. RESULTS: Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin. Likewise, it did not alter endogenous glucose production during high-dose insulin. However, 1-wk of exercise training increased both whole-body (P<0.05) and peripheral insulin sensitivity (P<0.0001) during high-dose insulin. CONCLUSION: Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral, not heptic insulin sensitivity. 相似文献
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Pouwels MJ Jacobs JR Span PN Lutterman JA Smits P Tack CJ 《The Journal of clinical endocrinology and metabolism》2001,86(5):2099-2103
Overactivity of the hexosamine biosynthetic pathway may underlie hyperglycemia-associated insulin resistance, but to date human studies are lacking. Hexosamine pathway activation can be mimicked by glucosamine (GlcN). In the present placebo-controlled study we determined whether GlcN infusion affects insulin resistance in vivo. In 18 healthy subjects, we applied the double forearm balance technique (infused arm vs. control arm) combined with the euglycemic hyperinsulinemic clamp (60 mU/m(2).min insulin) for at least 300 min. During the clamp, subjects received infusions in the brachial artery of 4 micromol/dL.min GlcN from 90-240 min (n = 6) or from 0-300 min (n = 6) or saline (placebo; n = 6). We studied the effects of GlcN on forearm glucose uptake (FGU; infused arm vs. control arm, and vs. placebo experiments) and on whole body glucose uptake. GlcN infusion raised the plasma GlcN concentration in the infusion arms to 0.42 +/- 0.14 and 0.81 +/- 0.46 mmol/L; plasma GlcN remained very low (< 0.07 mmol/L) in the control arms and in the placebo group. GlcN infusion did not change forearm blood flow. During insulin, FGU increased more than 10-fold. At all time points, FGU was similar in the GlcN-infused arm compared with the control arm and was not different from FGU in the placebo experiments. Similar results were obtained for forearm arteriovenous glucose differences or extraction and for whole body glucose uptake. Thus, despite relevant GlcN concentrations for 5 h in the infused forearm, GlcN had no effect on insulin-induced glucose uptake. These results do not support involvement of the hexosamine pathway in the regulation of insulin sensitivity in humans, at least not in the short-term setting. 相似文献
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Michael Schwarzer Steven L. Britton Lauren G. Koch Ulrik Wisloff Torsten Doenst 《Basic research in cardiology》2010,105(3):357-364
In patients, inactivity, obesity and insulin resistance are associated with increased incidence of heart failure. Rats selectively
bred for low (LCR) intrinsic aerobic exercise capacity show signs of the metabolic syndrome including insulin resistance,
compared to their counterparts bred for high intrinsic aerobic capacity (HCR). We reasoned that systemic insulin resistance
in LCR should translate to impaired substrate oxidation and reduced insulin sensitivity in the heart. Isolated hearts were
perfused in the working mode to analyze cardiac function, substrate oxidation patterns, insulin response, and oxygen consumption.
After 22 generations of selective breeding, LCR displayed reduction of exercise capacity (LCR vs. HCR: distance 280 ± 12 vs.
1,968 ± 63 m, time 19.5 ± 0.6 vs. 71.7 ± 1.4 min, speed 19.2 ± 0.3 vs. 45.3 ± 0.7 m/min; all p < 0.05). At 21 weeks, body weight (+34%), tibia length (+6%), heart weight (+31%), and heart weight to tibia length ratio
(+24%; all p < 0.05) were increased. LCR display higher random glucose, higher fasting glucose, and higher insulin levels in serum than
HCR indicating the presence of insulin resistance in LCR. Here, in contrast, isolated hearts showed no differences in glucose
(0.22 ± 0.02 μmol/min/g dry) or fatty acid oxidation (0.79 ± 0.10 μmol/min/g dry), oxygen consumption (28.3 ± 4.1 nmol O2/min/g dry) or cardiac power (18.6 ± 1.6 mW/g dry). Furthermore, sensitivity to insulin (Δglucose oxidation: +0.57 ± 0.095 μmol/min/g dry)
was not different between the two populations. Low intrinsic exercise capacity and systemic insulin resistance in rats are
not associated with changes in cardiac substrate oxidation, insulin sensitivity, oxygen consumption, or cardiac function.
The lack of cardiac insulin resistance in the face of systemic insulin resistance supports a concept of different pathomechanisms
for these two conditions. 相似文献
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BACKGROUND: Congestive heart failure (CHF) has previously been shown to be associated with insulin resistance and hyperinsulinemia. A beneficial effect of the non-selective beta-blocker carvedilol has been demonstrated in patients with CHF. However, whether the drug affects the insulin sensitivity (S(i)) is unknown. AIMS: To investigate whether treatment with carvedilol alters the S(i) in patients with CHF during a prospective, double-blinded, placebo-controlled study. METHODS AND RESULTS: The patients were randomized to receive either carvedilol (n=29) or matched placebo (n=17). Insulin and glucose responses were measured during a 0.3 g/kg intravenous glucose tolerance test, and S(i) was calculated according to Bergman's Minimal Model. Baseline S(i) values correlated significantly with body mass index (r=-0.42, P=0.002), plasma urate (r=-0.42, P=0.002), plasma HDL-cholesterol (r=0.39, P=0.003), maximal oxygen uptake (r=0.35, P=0.009), plasma triglycerides (r=-0.34, P=0.01) and weight (r=-0.29, P=0.03). During the study the insulin sensitivity was unchanged in the carvedilol group compared with placebo (2.63+/-1.45 to 2.38+/-1.64 vs. 2.81+/-2.36 to 2.48+/-1.84x10(-4) min(-1)/mUl(-1), P=0.83). CONCLUSION: Additional treatment with carvedilol is neutral with regard to influence the insulin sensitivity in patients with mild to moderate CHF. 相似文献
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B M Wentworth C Rhodes B Schnetzler D J Gross P A Halban L Villa-Komaroff 《Molecular and cellular endocrinology》1992,86(3):177-186
Rats and mice both express two, non-allelic, insulin genes. In the rat the ratio of the two preproinsulin mRNAs closely matches that of the mature insulin peptides. The experiments reported here demonstrate that this is not the case in the mouse. The relative amounts of the two murine proinsulin RNAs were measured by an S1 nuclease assay. The ratio of preproinsulin I mRNA to preproinsulin II mRNA was 4:1 in RNA extracted from the pancreas of mice fed ad libitum or fasted for 72 h. A similar value was found in mouse islets of Langerhans after maintenance in tissue culture for 48 h at either 2.8 or 16.7 mM glucose. The ratio of insulin I:insulin II peptides, assessed by separating the two insulins using reversed phase high-performance liquid chromatography, was approximately 1:3 in both pancreas and islets. Thus in the mouse, unlike the rat, the ratio of the two insulin peptides does not reflect that of the two preproinsulin mRNAs. 相似文献
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Obisesan TO Leeuwenburgh C Ferrell RE Phares DA McKenzie JA Prior SJ Hagberg JM 《Metabolism: clinical and experimental》2006,55(4):453-460
An etiologic role for chronic inflammation in the development of insulin resistance has been hypothesized. We determined whether the -732A/G and +219G/A C-reactive protein (CRP) gene variants affect insulin and glucose measures and whether these variants affect training-related changes in insulin sensitivity and glucose measures. Men and women 50 to 75 years old (n = 61) underwent baseline testing that included glucose tolerance, maximal oxygen consumption, body composition, CRP levels, and genotyping assessments. Tests were repeated after 24 weeks of aerobic exercise training. In bivariate analyses, CRP -732A/G G allele carriers had significantly lower baseline postprandial plasma glucose and after-training CRP levels. After exercise training, the -732A/G G allele carriers had approximately 28% increase in insulin sensitivity index (ISI) and approximately 26% reduction in insulin area under the curve (AUC), compared with the approximately 7% increase in ISI and approximately 15% reduction in insulin AUC in the A allele homozygotes (P = .03). The significant enhancement of ISI in -732A/G G allele carriers remained evident in analyses limited to those with normal glucose tolerance. Multivariate analyses adjusted for demographic and biologic variables confirmed the significant enhancement of training-induced improvement in ISI by the CRP gene variant. In addition, the CRP -732A/G and +219G/A haplotype significantly associated with training-induced improvements in ISI and insulin AUC in separate multivariate models. In conclusion, the CRP -732A/G variant modulates exercise training-related improvements in ISI and glucose AUC, and the haplotype of the CRP -732A/G and +219G/A variants significantly affected training-induced changes in ISI and insulin AUC. 相似文献
10.
GLP-1 does not acutely affect insulin sensitivity in healthy man 总被引:2,自引:1,他引:2
L. Ørskov M.D. J. J. Holst J. Møller C. Ørskov N. Møller K. G. M. M. Alberti O. Schmitz 《Diabetologia》1996,39(10):1227-1232
Summary Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7–36 amide) may have the direct effect of increasing
insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyperinsulinaemic
(0.8 mU · kg−1 · min−1), euglycaemic (5 mmol/l) clamp. Somatostatin (450 μg/h) was infused to suppress endogenous insulin secretion, and growth
hormone (3 ng · kg−1 · min−1) and glucagon (0.8 ng · kg−1 · min−1) were infused to maintain basal levels. GLP-1 (50 pmol · kg−1 · h−1) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1
levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the
clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69±1.17
vs 7.76±0.95 mg · kg−1 · min−1 at 150–180 min and 8.56±1.13 vs 8.55±0.68 mg · kg−1 · min−1 at 330–360 min) and there was no difference in isotopically determined hepatic glucose production rates (− 0.30±0.23 vs −0.16±0.22
mg · kg−1 · min−1 at 330–360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion
(1.43±0.23 vs 1.8±0.29 mmol/l), (ANOVA;p>0.60, in all instances). In conclusion, GLP-1 (7–36 amide) administered for 3 h, leading to circulating levels within the
physiological range, does not affect insulin sensitivity in healthy man. 相似文献
11.
Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention. 总被引:6,自引:0,他引:6
Jirí Hrebícek Vladimír Janout Jana Malincíková Dagmar Horáková Ludek Cízek 《The Journal of clinical endocrinology and metabolism》2002,87(1):144-147
The aim of the present study was to evaluate the recently defined simple insulin sensitivity check index QUICKI (Katz et al. 2000) for insulin resistance diagnostics in common clinical and epidemiological practice. Both the QUICKI (1/log insulin + log glycemia in mg/dL) and HOMA (insulin * glycemia in micromol/L/22.5) indexes were calculated from fasting values in 259 adult healthy volunteers and patients, and in 47 healthy and obese children of prepubertal age of both sexes. In adults, a fall in the QUICKI index (mean +/- SEM in healthy subjects = 0.366 +/- 0.029) as well as an increase in the HOMA index (in healthy subjects 1.57 +/- 0.87) corresponded to metabolic and clinical manifestations of insulin resistance in various groups of outpatients. The QUICKI index had lower dispersion variances and the 95% confidence limits displayed a higher discrimination capacity. Patients with glucose intolerance or diabetes, hyperlipidemia typical for insulin resistance, or with combination of these metabolic disorders were characterized by QUICKI index values that were significantly lower than those of healthy volunteers. The QUICKI index in healthy prepubertal children indicated a higher insulin resistance compared to adults (mean 0.339 +/- 0.020); an increase in the QUICKI index in obese children with BMI over 25 was not significant, although obese children showed a significant increase of serum leptin and triglycerides and a decrease of HDL-cholesterol. Adult patients with QUICKI index below 0.357 (which is at the lower limit of 95% confidence limits in healthy persons) represented a group with typical manifestations of metabolic syndrome, differing in these parameters significantly from the group of patients of comparable age with a QUICKI index greater than 0.357. The present study suggests suitability of the QUICKI index for diagnosis of insulin resistance in clinical and epidemiological practice. However, a normal QUICKI index range needs to be established for each laboratory with an appropriate control group because of significant interlaboratory variations in insulin determinations and/or possible differences in various populations. 相似文献
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Effects of antihypertensive drugs and exercise training on insulin sensitivity in spontaneously hypertensive rats. 总被引:3,自引:0,他引:3
Qi Guo Naoyoshi Minami Nobuyoshi Mori Makoto Nagasaka Osamu Ito Hajime Kurosawa Masayuki Kanazawa Masahiro Kohzuki 《Hypertension research》2008,31(3):525-533
We examined the effects of antihypertensive drugs, exercise training, and combinations thereof on insulin sensitivity (IS), and the association between this relation and sympathetic activity, muscle fiber composition, and capillary density in spontaneously hypertensive rats (SHR). Six-week-old male SHR were allocated to 7 groups: a control group (C), and groups treated with azelnidipine (Aze) (a calcium channel blocker), olmesartan (Olm) (an angiotensin II type 1 receptor blocker), exercise training (Exe), and combinations of drugs and exercise training (Aze+Exe, Olm+Exe, and Olm+Aze+Exe). At age 18 weeks, IS and sympathetic activity were evaluated by an euglycemic hyperinsulinemic glucose clamp technique and power spectral analysis of systolic blood pressure, respectively. After the experiments, capillary density and muscle fiber composition in soleus muscle were examined. Aze or Exe alone significantly increased IS associated with a significant reduction in sympathetic activity. Olm alone tended to increase IS with little change in sympathetic activity. Aze, Olm, or Exe significantly increased the capillary density and percentage of insulin-sensitive type I fiber. A combination of Aze and Exe or a combination of Olm and Exe tended to increase IS compared with each drug therapy alone. There were significant correlations between IS and sympathetic activity, capillary density, and the percentage of type I fiber in all the rats. We found that Aze improved IS more substantially compared with Olm in SHR. We also found that Aze, Olm, Exe, and combinations thereof improved IS, probably through the modulation of sympathetic activity or capillarity and muscle fiber type in skeletal muscles. 相似文献
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Raloxifene does not modify insulin sensitivity and glucose metabolism in postmenopausal women 总被引:3,自引:0,他引:3
Cagnacci A Paoletti AM Zanni A Arangino S Ibba G Orrù M Melis GB Volpe A 《The Journal of clinical endocrinology and metabolism》2002,87(9):4117-4121
Insulin sensitivity (Si), glucose tolerance, and lipid metabolism were investigated in osteopenic postmenopausal women before and after 6 months of treatment with raloxifene (60 mg/d) or placebo. In a group of women (n = 34), glucose metabolism was evaluated by means of an oral glucose tolerance test (75 g). In another group of women (n = 24), Si and peripheral glucose utilization not dependent on insulin were evaluated by means of a frequently sampled iv glucose tolerance test associated with the minimal model method. No metabolic modification was observed in women receiving placebo. Raloxifene did not significantly modify high density lipoprotein-cholesterol and triglycerides, whereas it significantly decreased low density lipoprotein (LDL) cholesterol (4.84 +/- 0.34 mmol/liter vs. 3.83 +/- 0.49 mmol/liter; P = 0.014) and LDL/high density lipoprotein cholesterol ratio (3.21 +/- 0.31 mmol/liter vs. 2.46 +/- 0.44 mmol/liter; P = 0.012). Fasting levels and responses to the oral glucose tolerance test of glucose, insulin, C-peptide, and C-peptide/insulin were not modified by raloxifene. Similarly, raloxifene did not modify Si (4.22 +/- 4.1 vs. 5.13 +/- 1.75), or insulin (0.025 +/- 0.003 vs. 0.019 +/- 0.002). The present data show that in osteopenic postmenopausal women raloxifene reduces LDL levels but does not modify insulin sensitivity and glucose metabolism. 相似文献
14.
The present study characterized large-artery properties in patients with isolated systolic hypertension (ISH) and determined the efficacy of exercise training in modifying these properties. Twenty patients (10 male and 10 female) with stage I ISH and 20 age- and gender-matched control subjects were recruited, and large-artery properties were assessed noninvasively. Ten ISH patients (5 male and 5 female) were enrolled in a randomized crossover study comparing 8 weeks of moderate intensity cycling with 8 weeks of sedentary activity. Brachial and carotid systolic, diastolic, mean, and pulse pressures were higher in the ISH group than in the control group. Systemic arterial compliance (0.43+/-0.04 versus 0.29+/-0.02 arbitrary compliance units for the control versus ISH groups, respectively; P=0.01) was lower, and carotid-to-femoral pulse-wave velocity (9.67+/-0.36 versus 11.43+/-0.51 m. s(-1) for the control versus ISH groups, respectively; P=0.007), input impedance (2.39+/-0.19 versus 3.27+/-0.34 mm Hg. s. cm(-1) for the control versus ISH groups, respectively; P=0.04), and characteristic impedance (1.67+/-0.17 versus 2.34+/-0.27 mm Hg. s. cm(-1) for the control versus ISH groups, respectively; P=0.05) were higher in the ISH group than in the control group. Training increased maximal oxygen consumption by 13+/-5% (P=0.04) and maximum workload by 8+/-4% (P=0.05); however, there was no effect on arterial mechanical properties, blood lipids, or left ventricular mass or function. These results suggest that the large-artery stiffening associated with ISH is resistant to modification through short-term aerobic training. 相似文献
15.
Brady LM Gower BA Lovegrove SS Williams CM Lovegrove JA 《International journal of obesity (2005)》2004,28(2):222-227
OBJECTIVE: To compare insulin sensitivity (Si) from a frequently sampled intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses with surrogate measures of insulin sensitivity and resistance and to compare features of the metabolic syndrome between Caucasians and Indian Asians living in the UK. SUBJECTS: In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si of 2.85+/-0.37. MEASUREMENTS: Si was determined from an FSIGT with subsequent minimal model analysis. The concentrations of insulin, glucose and nonesterified fatty acids (NEFA) were analysed in fasting plasma and used to calculate surrogate measure of insulin sensitivity (quantitative insulin sensitivity check index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index, fasting insulin, insulin-to-glucose ratio). Plasma concentrations of triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and low density cholesterol, (LDL-C) were also measured in the fasted state. Anthropometric measurements were conducted to determine body-fat distribution. RESULTS: Correlation analysis identified the strongest relationship between Si and the revised QUICKI (r=0.67; P=0.000). Significant associations were also observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009), FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive (Si) than the Caucasian group (P=0.02). CONCLUSION: The revised QUICKI demonstrated a statistically strong relationship with the minimal model. However, it was unable to differentiate between insulin-sensitive and -resistant groups in this study. Future larger studies in population groups with varying degrees of insulin sensitivity are recommended to investigate the general applicability of the revised QUICKI surrogate technique. 相似文献
16.
Katsuki A Sumida Y Gabazza EC Murashima S Urakawa H Morioka K Kitagawa N Tanaka T Araki-Sasaki R Hori Y Nakatani K Yano Y Adachi Y 《The Journal of clinical endocrinology and metabolism》2002,87(6):2906-2908
To investigate whether quantitative insulin sensitivity check index (QUICKI) would be useful as an index of insulin resistance during the clinical course of type 2 diabetes mellitus, correlation between QUICKI and the index of the euglycemic hyperinsulinemic clamp study [clamp insulin resistance (clamp IR)] was evaluated in 60 patients with type 2 diabetes mellitus before and after treatment. The therapy program consisted of diet (1440-1720 kcal/d) and exercise (walking 10,000 steps daily) for 6 wk. QUICKI and clamp IR were significantly correlated before (r = 0.598, P < 0.0001) and after (r = 0.583, P < 0.0001) treatment. Neither the slope nor the intercept of the linear correlation between QUICKI and clamp IR measured before treatment was significantly different from those measured after treatment (slopes; F = 0.002, P = 0.96, intercepts; F = 2.65, P = 0.11). During treatment, the values of both QUICKI (8% change; P < 0.0001) and clamp IR (38% change; P < 0.0001) significantly increased and their changes were significantly correlated (r = 0.415, P < 0.01). In conclusion, QUICKI may become a useful method for the follow-up of insulin resistance during the treatment of patients with type 2 diabetes mellitus. 相似文献
17.
Nardi R Scanelli G Corrao S Iori I Mathieu G Cataldi Amatrian R 《European Journal of Internal Medicine》2007,18(5):359-368
Internal medicine patients are mostly elderly; they have multiple co-morbidities, which are usually chronic, rather than self-limiting or acute diseases. Neither administrative indicators nor co-morbidity indexes, though validated in elderly patients, are able to completely define these "complex" patients or to allow physicians to correctly "cope" with them. For the complex patients found in internal medicine wards, internists need not only to find the best diagnosis and treatment, but also to apply a complex intervention (i.e., a comprehensive assessment and both continuous and multi-disciplinary care) in order to maintain their health and ability to function and to prevent or delay disability, frailty, and displacement from home and community. The aim of this review is to underscore the differences between the concepts of co-morbidity and complexity, to discuss instruments for their measurement, and to highlight related implications, areas of uncertainty, and the responsibilities of internists in the assessment and management of inpatients of their wards. The conclusion we come to is that it is mandatory to shift from a finance/administrative-based management system to a clinical process model (clinical governance) driven by the quality of the medical outcome and the cost of achieving that outcome. From a "complexity theory" standpoint, patient-centered care and collaboration can be seen as simple rules that guide desirable behaviors in a complex system. By exploring the real complexity of our patients, we exercise the holistic, anthropologic medicine of the person that is internal medicine. 相似文献
18.
Perreault L Bergman BC Hunerdosse DM Howard DJ Eckel RH 《Metabolism: clinical and experimental》2011,60(8):1107-1114
Animal data suggest that males, in particular, rely on peroxisome proliferator activated receptor-α activity to maintain normal muscle triglyceride metabolism. We sought to examine whether this was also true in men vs women and its relationship to insulin sensitivity (Si). Normolipidemic obese men (n = 9) and women (n = 9) underwent an assessment of Si (intravenous glucose tolerance test) and intramuscular triglyceride (IMTG) metabolism (gas chromatography/mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry from plasma and muscle biopsies taken after infusion of [U-13C]palmitate) before and after 12 weeks of fenofibrate treatment. Women were more insulin sensitive (Si: 5.2 ± 0.7 vs 2.4 ± 0.4 ×10−4/ μU/mL, W vs M, P < .01) at baseline despite similar IMTG concentration (41.9 ± 15.5 vs 30.8 ± 5.1 μg/mg dry weight, W vs M, P = .43) and IMTG fractional synthesis rate (FSR) (0.27%/h ± 0.07%/h vs 0.35%/h ± 0.06%/h, W vs M, P = .41) as men. Fenofibrate enhanced FSR in men (0.35 ± 0.06 to 0.54 ± 0.06, P = .05), with no such change seen in women (0.27 ± 0.07 to 0.32 ± 0.13, P = .73) and no change in IMTG concentration in either group (23.0 ± 3.9 in M, P = .26 vs baseline; 36.3 ± 12.0 in W, P = .79 vs baseline). Insulin sensitivity was unaffected by fenofibrate (P ≥ .68). Lower percentage saturation of IMTG in women vs men before (29.1% ± 2.3% vs 35.2% ± 1.7%, P = .06) and after (27.3% ± 2.8% vs 35.1% ± 1.9%, P = .04) fenofibrate most closely related to their greater Si (R2 = 0.34, P = .10) and was largely unchanged by the drug. Peroxisome proliferator activated receptor-α agonist therapy had little effect on IMTG metabolism in men or women. Intramuscular triglyceride saturation, rather than IMTG concentration or FSR, most closely (but not significantly) related to Si and was unchanged by fenofibrate administration. 相似文献
19.
Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients 总被引:4,自引:0,他引:4
Gannagé-Yared MH Azar RR Amm-Azar M Khalifé S Germanos-Haddad M Neemtallah R Halaby G 《Metabolism: clinical and experimental》2005,54(7):947-951
BACKGROUND: The effect of statins on insulin resistance is controversial and poorly studied in nondiabetic subjects. In addition, the effect of statins on leptin and adiponectin has never been studied. METHODS: Forty healthy nondiabetic volunteers (22 men and 18 women) aged 28 to 72 were randomized either to placebo or pravastatin 40 mg daily for a 12-week period. Insulin resistance, assessed using the Quantitative Insulin Sensitivity Check Index (QUICKI), as well as serum leptin and adiponectin levels, was measured at baseline and at the end of therapy. RESULTS: Pravastatin treatment decreased total cholesterol, low-density lipoprotein cholesterol, and triglycerides levels by 24%, 32%, and 14%, respectively ( P < .05 for all), but did not affect glucose and insulin levels, the (QUICKI) index, and adiponectin and leptin levels. When stratification was performed according to QUICKI index or sex, no significant differences were observed in the prevalues and postvalues of leptin, adiponectin, or QUICKI index in the pravastatin group. Adiponectin, leptin, and QUICKI index were statistically higher in women than in men ( P < .001 for both variables). Adiponectin was negatively correlated with body mass index (BMI; r = -0.39, P < .05) and positively correlated with the QUICKI index ( r = 0.54, P < .001) and with high-density lipoprotein cholesterol ( r = 0.50, P < .01). The relation between adiponectin and QUICKI index remained significant after adjustment for sex and BMI ( P = .005 and P = .007, respectively). Leptin was only related to BMI ( r = 0.57, P < .001) and to sex ( P < .001) with no significant correlations with lipid parameters or QUICKI index. Both sex and BMI are independent predictors of leptin ( P < .001 and P < .001). CONCLUSION: A 12-week treatment with pravastatin 40 mg/d does not change the QUICKI index and leptin and adiponectin levels in healthy volunteers. In addition, our results emphasize the importance of sex and BMI in the determination of both adiponectin and leptin. Adiponectin was also related to QUICKI index, whereas this relation was not found with leptin. 相似文献
20.
The relationship between serum dopamine-beta-hydroxylase (DBH) activity and sympathetic nervous system activation in response to insulin-induced hypoglycemia was investigated in healthy young male and female volunteers. Serum DBH activity and glucose levels were measured in blood samples obtained 30 min before and 90 min after the iv administration of regular insulin or placebo. All subjects developed significant hypoglycemia in response to the insulin and manifested signs of sympathetic activation, including increased heart rate, diaphoresis, and lightheadedness. However, despite obvious clinical manifestations of increased sympathetic activity, none of the subjects exhibited a significant alteration in serum DBH activity either in comparison to baseline or placebo values. These data question the suitability of serum DBH measurements for assessing adrenomedullary function in man. 相似文献