Reduced postprandial bone resorption and greater rise in GLP-1 in overweight and obese individuals after an α-glucosidase inhibitor: a double-blinded randomized crossover trial.

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. INTRODUCTION: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. METHODS: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21-59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. RESULTS: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). CONCLUSION: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. INTRODUCTION: Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. METHODS: This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. RESULTS: Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05). CONCLUSION: The decline in Ct thickness was prevented with higher vitamin D3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

Hormonal and dietary influences on true fractional calcium absorption in women: role of obesity.

UNLABELLED: The goal in this study was to examine the hormonal and dietary predictors of true fractional Ca absorption (TFCA) in adult women and to determine whether TFCA differs due to body weight. Results showed that TFCA is higher in obese individuals and dietary fat, estradiol, and 1,25-dihydroxy vitamin D are the most significant positive predictors of TFCA in adult women. INTRODUCTION: Calcium absorption is an important determinant of calcium balance and is influenced by several factors. Previous studies have identified that age, intake of protein, fat and fiber, and hormones such as 1, 25-dihyroxyvitamin D (1,25(OH)(2)D(3)) influence absorption. The determinants of TFCA using the double isotope method, the gold standard estimate of absorption, have not been examined previously in adult women nor has the role of obesity been addressed. METHODS: In this study, we examined the hormonal and dietary predictors of TFCA in adult women with a wide range of age, body weights, and nutrient intake. TFCA was measured using dual stable isotope ((42)Ca and (43)Ca) technique. Serum was analyzed for bone-regulating hormones, and dietary information was obtained through food records. The independent dietary factors and hormonal predictors (25-hydroxyvitamin D, 1,25(OH)(2)D(3), parathyroid hormone, and estradiol) of TFCA were analyzed using multiple regression analysis. RESULTS: Two hundred twenty-nine women aged 54 ± 11 years old (24-75 years) and with BMI of 31 ± 7.0 kg/m(2) were eligible and were categorized into tertiles of body mass index (BMI) into leaner, overweight, and obese. In the entire group of women, total fat intake, estradiol, and 1,25(OH)(2)D(3) are significant positive predictors (p < 0.05). As expected, age is a significant negative predictor of TFCA (R (2) = 26%). TFCA is higher in obese women compared to non-obese women (p < 0.05). CONCLUSION: Together, these data show that dietary fat is the most significant positive predictor of TFCA which may have implications for dietary intake for non-obese individuals who are more likely to have lower and potentially compromised Ca absorption.

Detecting climatic change signals: are there any "fingerprints"?

Projected changes in the Earth's climate can be driven from a combined set of forcing factors consisting of regionally heterogeneous anthropogenic and natural aerosols and land use changes, as well as global-scale influences from solar variability and transient increases in human-produced greenhouse gases. Thus, validation of climate model projections that are driven only by increases in greenhouse gases can be inconsistent when one attempts the validation by looking for a regional or time-evolving "fingerprint" of such projected changes in real climatic data. Until climate models are driven by time-evolving, combined, multiple, and heterogeneous forcing factors, the best global climatic change "fingerprint" will probably remain a many-decades average of hemi-spheric- to global-scale trends in surface air temperatures. Century-long global warming (or cooling) trends of 0.5 degrees C appear to have occurred infrequently over the past several thousand years-perhaps only once or twice a millennium, as proxy records suggest. This implies an 80 to 90 percent heuristic likelihood that the 20th-century 0.5 +/- 0.2 degrees C warming trend is not a wholly natural climatic fluctuation.

The greenhouse effect: science and policy.

Global warming from the increase in greenhouse gases has become a major scientific and political issue during the past decade. That infrared radiation is trapped by greenhouse gases and particles in a planetary atmosphere and that the atmospheric CO(2) level has increased by some 25 percent since 1850 because of fossil fuel combustion and land use (largely deforestation) are not controversial; levels of other trace greenhouse gases such as methane and chlorofluorocarbons have increased by even larger factors. Estimates of present and future effects, however, have significant uncertainties. There have also recently been controversial claims that a global warming signal has been detected. Results from most recent climatic models suggest that global average surface temperatures will increase by some 2 degrees to 6 degrees C during the next century, but future changes in greenhouse gas concentrations and feedback processes not properly accounted for in the models could produce greater or smaller increases. Sea level rises of 0.5 to 1.5 meters are typically projected for the next century, but there is a small probability of greater or even negative change. Forecasts of the distribution of variables such as soil moisture or precipitation patterns have even greater uncertainties. Policy responses range from engineering countermeasures to passive adaptation to prevention and a "law of the atmosphere." One approach is to implement those policies now that will reduce emissions of greenhouse gases and have additional societal benefits. Whether the uncertainties are large enough to suggest delaying policy responses is not a scientific question per se, but a value judgment.

Ecology and climate: research strategies and implications.

Natural and anthropogenic global changes are associated with substantial ecological disturbances. Multiscale interconnections among disciplines studying the biotic and abiotic effects of such disturbances are needed. Three research paradigms traditionally have been used and are reviewed here: scale-up, scale-down, and scale-up with embedded scale-down components. None of these approaches by themselves can provide the most reliable ecological assessments. A fourth research paradigm, called strategic cyclical scaling (SCS), is relatively more effective. SCS involves continuous cycling between large- and small-scale studies, thereby offering improved understanding of the behavior of complex environmental systems and allowing more reliable forecast capabilities for analyzing the ecological consequences of global changes.

Carbon dioxide and climate: the importance of realistic geography in estimating the transient temperature response.

Results obtained from a detailed air-sea-ice climate model for an instantaneous increase in the atmospheric carbon dioxide content are used to estimate the transient surface temperature response for several time-dependent carbon dioxide increase scenarios. The inclusion of realistic variations of land fraction and ocean mixing with latitude is found to limit the applicability of steady- state simulations as approximate guides to the actual time-dependent temperature response, particularly when the regional response is considered.

Atmospheric carbon dioxide and aerosols: effects of large increases on global climate.

Effects on the global temperature of large increases in carbon dioxide and aerosol densities in the atmosphere of Earth have been computed. It is found that, although the addition of carbon dioxide in the atmosphere does increase the surface temperature, the rate of temperature increase diminishes with increasing carbon dioxide in the atmosphere. For aerosols, however, the net effect of increase in density is to reduce the surface temperature of Earth. Because of the exponential dependence of the backscattering, the rate of temperature decrease is augmented with increasing aerosol content. An increase by only a factor of 4 in global aerosol background concentration may be sufficient to reduce the surface temperature by as much as 3.5 degrees K. If sustained over a period of several years, such a temperature decrease over the whole globe is believed to be sufficient to trigger an ice age.

An ice-free cretaceous? Results from climate model simulations.

We have quantitatively investigated the mechanisms that could explain the warm, equable climate that is believed to have been typical of the mid-Cretaceous (100 million years ago). By performing simulations with a climate model based on zonal energy balance, we demonstrate that past changes in geography were important in bringing about climatic change. However, the meridional distribution of Cretaceous temperatures cannot be successfully simulated unless additional physical "feedback mechanisms" are included in the model. These mechanisms may involve cloud and meridional heat transport changes. We also conclude that paleoclimatologists should reexamine carefully both existing data and their interpretations with regard to reconstruction of Cretaceous tropical and polar surface temperatures.

Circulating zearalenone and its metabolites differ in women due to body mass index and food intake.

The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ±â€¯9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (<115 g/d) meat consumption had higher conjugated serum ZEA metabolite concentrations (p < 0.05). Intakes of other food groups (i.e., dairy, cereal, etc.) were not associated with ZEA metabolites. These findings indicate that ZEA and its metabolites are detectable in nearly all women and concentrations are associated with greater meat intake, and influenced by body mass index. Determining how the food supply influences human concentrations of ZEA metabolites is warranted, as well as determining vulnerable populations.

The effects of triiodothyronine, hydrocortisone and insulin on lipid synthesis by cultured fibroblasts preincubated in a serum-free medium.

Studies of lipid metabolism in cell cultures are usually carried out after preincubation of cells in media containing lipoprotein-deficient or delipidated serum. The artifacts produced during delipidation prevent the standardization of assays and the study of the role of hormones on lipid metabolism. We studied the effects of triiodothyronine, hydrocortisone, insulin and their combination on cholesterol and fatty acid synthesis in cultured human skin fibroblasts preincubated for 24 h in an artificial medium (medium A) consisting of equal volumes of Dulbecco's modified Eagle's and Ham's F-12 media enriched with transferrin, biotin and calcium pantothenate. In cells preincubated in medium A the incorporation of acetate to cholesterol and the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase were much lower than in cells preincubated in standard medium containing lipoprotein-deficient serum. Addition of the three hormones caused a marked stimulation of the incorporation of acetate to cholesterol (from 3.1 to 17.7 pmol/min per mg protein), an activity similar to that in cells preincubated in lipoprotein-deficient serum plus hormones. The stimulatory effect of the hormones on HMG-CoA reductase activity was smaller, from 11 to 26 pmol/min per mg protein compared to 83 pmol/min per mg protein in cells preincubated in lipoprotein-deficient serum plus hormones. Most of the stimulatory effect was due to insulin. The lack of coordinate response between these two parameters in cells preincubated in artificial medium could not be explained by (a) stimulation of a post-mevalonate step as measured by the incorporation of mevalonate to cholesterol; (b) the in vitro inactivation of HMG-CoA reductase by phosphorylation: incubation of fibroblast microsomes with Escherichia coli alkaline phosphatase resulted in a decrease in HMG-CoA reductase activity, in contrast to an increase in hepatic microsomes; (c) the presence of inhibitors of HMG-CoA reductase in the microsomal extract. In cells preincubated in medium A the incorporation of acetate to fatty acids and the activities of acetyl-CoA carboxylase and fatty acid synthetase were approximately equal to that of cells preincubated in standard medium containing lipoprotein-deficient serum. Hormones added to medium A caused a stimulation of incorporation of acetate to fatty acids (from 5.1 to 19.8 pmol/min per mg protein), the activity of acetyl-CoA carboxylase (from 494 to 820 pmol/min per mg protein) and of fatty acid synthetase (from 300 to 678 pmol/mg protein). These values were significantly higher than those obtained in cells preincubated with lipoprotein-deficient serum with or without hormones.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes, exercise, and atherosclerosis.

Regular exercise may diminish the risk for atherosclerotic vascular disease in patients with non-insulin-dependent (type II) diabetes and in the general population. The basis for this effect of exercise may be its ability to diminish or prevent hyperinsulinemia, insulin resistance, and/or increases in intra-abdominal adipose mass. These abnormalities are associated with premature atherosclerotic vascular disease, essential hypertension, type II diabetes, and certain dyslipoproteinemias, and most likely precede them. They also have been implicated in the pathogenesis of these disorders. We propose that the high prevalence of hyperinsulinemia and insulin resistance in individuals leading a western life-style accounts for the reported benefit of physical activity in preventing coronary heart disease in the general population. We also propose that exercise (and diet) are most likely to be effective when initiated in young individuals, before the onset of irreversible vascular alterations, and when life-style changes may be more acceptable. Early identification of such individuals may be possible on the basis of family history, the presence of components of the hyperinsulinemia-insulin resistance syndrome, and/or central obesity. One such group that may already have been identified is women with gestational diabetes.

Studies on the relationship between insulin concentrations and insulin action.

The relationship between insulin concentrations and insulin effects was assessed using a 30-min steady-state perfusion of insulin across the human forearm and a 90-min recovery period in 17 normal men. During perfusion, calculated insulin increments in forearm arterial plasma insulin were 87 +/- 4 (group I), 161 +/- 17 (group II), and 333 +/- 55 microU/ml (group III), respectively. Measured venous insulin increments were 33 +/- 4, 66 +/- 6, and 231 +/- 27 microU/ml. During perfusion, venous and arterial increments were linearly related (r = 0.88, P less than 0.001). With discontinuation of perfusion, venous increments of insulin became undetectable after 15 min in groups I and II, and after 30 min in group III. Of the total microunits of insulin perfused, 46.0 +/- 11.0%, 45.3 +/- 9.4%, and 36.5 +/- 4.8%, respectively, remained unaccounted for 90 min after perfusion. Effects of insulin on arteriovenous differences of FFA and potassium persisted throughout the recovery period, with peak effects occurring after perfusion for all groups. Estimated interstitial insulin levels in the three groups fell below 10 microU/ml by 45, 60, and 90 min after perfusion, respectively. Although peripheral tissues had a significant capacity to sequester insulin, the persistence of biologic effects was not consistent with increased concentrations within the interstitial spaces. Effects of insulin upon glucose waned first, followed by effects upon potassium and then lipolysis.

Exercise in therapy and prevention of type II diabetes. Implications for blacks.

The rationale for the use of exercise in the treatment of type II (non-insulin-dependent) diabetes and its special implications for Blacks are reviewed herein. When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia. In addition, it may be a useful adjunct to diet in producing weight loss. The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity. Benefits are short lived after discontinuing exercise. Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program. For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis. Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution. Type II diabetes is more common in Blacks than in the general population. In most instances, it is associated with cardiovascular risk factors benefited by exercise. Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it.

Ten-year experience with an exercise-based outpatient life-style modification program in the treatment of diabetes mellitus.

Exercise is frequently recommended in the treatment of diabetes mellitus. Nevertheless, its use has been limited in clinical practice, and concerns about safety and efficacy persist. We have reviewed a 10-yr experience with 255 patients enrolled in a comprehensive diabetes program that emphasized physical training. A low maximal oxygen uptake (VO2max) was found in patients with non-insulin-dependent diabetes mellitus compared with sedentary control subjects. This was not accounted for by autonomic neuropathy and is unlikely to be due to subtle differences in life-style. Exercise-related proteinuria was common and occurred in 29% of patients and was associated with higher blood pressure levels at rest and during exercise, impaired VO2max, and decreased R-R interval variation. Regular exercise was associated with a modest decrease in resting and exercise blood pressure. Glycosylated hemoglobin levels and plasma triglycerides improved only in patients with non-insulin-dependent diabetes mellitus. Insulin requirements were significantly reduced in patients with insulin-dependent diabetes mellitus. Compliance for up to 3 mo in the program was acceptable but longer-term compliance was poor. Serious complications during the program were rare. Our experience suggests a program of regular aerobic training can be safely and effectively used in an outpatient population with diabetes mellitus for up to 3 mo.

Vitamin D supplementation during short-term caloric restriction in healthy overweight/obese older women: Effect on glycemic indices and serum osteocalcin levels.

The effect of vitamin D supplementation and caloric restriction (CR) on glycemic indices and osteocalcin (OC) is not clear. In this randomized controlled double blind trial, we examined whether vitamin D3 supplementation at 2500 IU/d (D) or placebo has differential effects on markers of insulin sensitivity and bone turnover in overweight/obese postmenopausal women during 6 weeks of caloric restriction (weight loss; WL, n = 39) compared to weight maintenance (WM, n = 37). Seventy-six women (57 ± 6 years) completed this study and the WL groups lost 4 ± 1% of body weight. Baseline serum 25-hydroxyvitamin D (25OHD) was 24.8 ± 5.6 ng/mL at baseline; the rise was greatest in WL-D group (p < 0.05). There was an interaction between vitamin D intake and weight on serum OC, insulin, glucose and markers of insulin sensitivity (p < 0.05). The change in OC was explained by changes in serum 25OHD and insulin (model R(2) = 25.6%). Overall, vitamin D supplementation and CR influence serum osteocalcin levels and modestly favor improvements in insulin sensitivity.

Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction.

Low calcium absorption is associated with low bone mass and fracture. In this study, we use gold standard methods of fractional calcium absorption (FCA) to determine whether polymorphisms of intestinal receptors, vitamin D receptor (VDR) and estrogen receptor α (ESR1), influence the response to energy restriction. Fractional calcium absorption was measured using dual stable isotopes ((42)Ca and (43)Ca) in women given adequate calcium and vitamin D and examined at baseline and after 6 weeks of energy restriction or no intervention. After genotyping, the relationship between VDR and ESR1 genotypes/haplotypes and FCA response was assessed using several genetic models. One-hundred and sixty-eight women (53 ± 11 years of age) were included in this analysis. The ESR1 polymorphisms, PvuII and XbaI and VDR polymorphisms (TaqI, ApaI) did not significantly influence FCA. The BB genotype of the VDR polymorphism, BsmI, was associated with a greater decrease in FCA than the Bb/bb genotype. Multiple linear regression showed that the BsmI polymorphism or the VDR haplotype, BAt, in addition to changes in weight and vitamin D intake explained ~16% of the variation in changes in FCA. In conclusion, the reduction in calcium absorption due to energy restriction is greatest for those with the BB genotype. Previous candidate gene studies show that VDR polymorphisms are associated with higher risk for osteoporosis, and the current study supports the notion that the BsmI polymorphism in intestinal VDR may be contributing to alterations in bone health.

Aromatization of androgens by muscle and adipose tissue in vivo.

[7-3HA1Androstenedione and [4-14C]estrone or [7-3H]testosterone and [14C]estradiol were infused at constant rates into brachial arm veins of 15 normal men. During the infusions blood samples were obtained from the brachial artery, a deep vein draining primarily muscle, and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In seven men the mean +/- SE value for the fractional conversion of androstene tissue. In eight men the mean +/- SE value for the fractional conversion of testosterone to estradiol was 0.0007 +/- 0.0001 for muscle and 0.0012 +/- 0.0002 for adipose tissue. Both of these values were significantly (P less than 0.01) less than the respective values of androstenedione aromatization to estrone. If constancy of tissue aromatization throughout the body is assumed, the muscle accounts for 25-30% and adipose tissue for 10-15% of the total extragonadal aromatization of androgens to estrogens.

In vivo studies on the metabolism of estrogens by muscle and adipose tissue of normal males.

3H and 14C-Labeled estrone, estradiol, and estrone sulfate were infused at constant rates into brachial arm veins of normal men. In any one experiment, subjects generally received two estrogens, one 3H-labeled and one 14C-labeled. During the infusions, blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In 11 men the mean +/- SE value for the metabolism of estrone by muscle, rho1,0A,M(rho1,0A,M = fraction of estrone in arterial blood which is metabolized by muscle) is 0.17 +/- 0.02 which is not (P greater than 0.1) significantly different from the mean +/- SE value for the metabolism of estrone by adipose tissue, rho1,0A,AT, 0.22 +/- 0.02. Both tissues convert estrone to estradiol, rho1,2A,M(rho1,2A,M = fraction of estrone in arterial blood which is measured as estradiol in venous blood draining muscle) is 0.026 +/- 0.005 and rho1,2A,AT is 0.022 +/- 0.005. Both tissues metabolized estradiol, rho2,0A,M = 0.09 +/- 0.01 and rho2,0A,AT = 0.12 +/- 0.03, and for each tissue the metabolism of estradiol was significantly less than that of estrone (P less than 0.01). Estradiol was converted to estrone by both tissues; rho2,1A,M = 0.007 +/- 0.003 and rho 2,1A,AT = 0.017 +/- 0.003. For estrone sulfate, tissue metabolism could be demonstrated in only 2 of 5 infusions; the values being 0.04 and 0.03, and 0.04 and 0.03 in muscle and adipose tissue, respectively. In only 1 of 3 infusions was evidence obtained for the conversion, by muscle, of estrone sulfate to estrone, rhoS,1A,M = 0.003 and only in one of the 5 subjects was adipose tissue active in this conversion. In no instance were we able to show conversion of estrone sulfate to estradiol by either tissue. In only 1 of 3 infusions could we measure demonstrable conversion of estrone to estrone sulfate by adipose tissue, rho1,SA,AT = 0.02, and we could not demonstrate conversion of estrone to estrone sulfate by muscle or of estradiol to estrone sulfate by either tissue. Both muscle and adipose tissue metabolize and interconvert the free estrogens, estrone and estradiol. The total metabolism by both tissues accounts for 5-10% of the overall metabolic clearance rate of each steroid. The formation of estrone sulfate from estrone and estradiol and the hydrolysis of estrone sulfate occurs to only a minor extent in these tissues.

Dexamethasone increases leptin expression in humans in vivo.

The effect of 2 days of oral dexamethasone administration (0.75 mg twice daily) on leptin expression in healthy volunteers was tested. Dexamethasone increased the relative abundance of leptin messenger RNA in abdominal and gluteal adipose tissues by approximately 70% (P < 0.05). Dexamethasone also significantly increased serum leptin (+ 80%) and insulin concentration (+ 83%) but did not affect serum glucose. We conclude that a hypercortisolemic/hyperinsulinemic state up-regulates leptin expression at the messenger RNA level in humans.