Homeostatic Index Of Insulin Resistance Research Articles

Resveratrol Mitigates Diabetic Testicular Dysfunction, Endocrine Deficits, and Insulin Resistance via Suppression of Sperm-Endocrine Aberrations and Oxidative Inflammation in Rats

Diabetes mellitus (DM) provokes reproductive impairments through endocrine disturbance, sperm deficits, and testicular oxidative inflammation. The study investigated the reproductive protective effects of resveratrol (RSV) against testicular oxidative inflammation, sperm/endocrine deficits, and insulin resistance in streptozotocin- (STZ-, 65 mg/kg) induced DM rat model. Male rats were randomly divided into 4 groups ( n = 6 ): control, DM, RSV (150 mg/kg bw, orally), and RSV+DM group (21 days). The nontreated DM rats showed marked decreases in serum insulin, reproductive hormones (T, LH, and FSH), and lipid profile levels compared to control. The homeostatic index of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were adversely modulated. Sperm count and motility were profoundly decreased, whereas sperm abnormality was significantly increased. The testicular activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) level, along with inflammatory cytokines (TNF-α, IL-6, IL-4, and IL-10) were significantly dysregulated. The DM induced histopathological lesions compared to control rats. Interestingly, the RSV administration to DM rats attenuated the altered reproductive parameters, restored antioxidant mechanism, and anti-inflammatory responses with improved insulin resistance. RSV could prevent DM-induced reproductive deficits and insulin resistance via modulating oxidative stress-mediated testicular inflammation in rats.

Dietary Sinapic Acid Alleviates Adiposity and Inflammation in Diet-Induced Obese Mice.

Sinapic acid (SA), a hydroxycinnamic acid, is known to confer protection against oxidative stress, inflammation, diabetes, and liver disease. However, the effectiveness of SA in improving obesity remains obscure. Therefore, this study evaluated anti-obesity efficacy of SA and to elucidate its mechanism of action. Male mice were maintained for 16 weeks on high-fat diet (HFD) alone or with SA (0.004%, w/w) and bodyweight, fat mass, adipocyte size, food intake, and biochemical and molecular markers were evaluated. SA-supplemented mice demonstrated markedly decreased fat mass and adipocyte size compared to unsupplemented group, without any changes in bodyweight and food intake between the two groups. Plasma adipocytokines levels including leptin, resistin, monocyte chemoattractant protein (MCP)-1 and interleukin-6 were also markedly reduced by SA supplementation. SA tended to lower plasma insulin level and improved homeostatic index of insulin resistance and intraperitoneal glucose tolerance test in HFD-induced obese mice. The anti-adiposity effect of SA was maybe owing to down-regulation of the mRNA expression of lipogenic genes, including acetyl coenzyme A (CoA) carboxylase, fatty acid synthesis, stearoyl-CoA desaturase 1, and phosphatidate phosphatase, and peroxisome proliferator-activated receptor γ, a transcription factor responsible for governing lipid metabolism, in adipose tissues. SA significantly down-regulated pro-inflammatory nuclear factor kappa B, MCP-1, tumor necrosis factor-α, and Toll-like receptor 4 mRNA expression in adipose tissue. Thus, SA could be beneficial for the development of functional foods or herbal medications to combat obesity.

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes.

Tea polysaccharide (TPS) is a bioactive compound that has attracted increasing attention for its health effect on regulating the metabolism of glucose and lipid. Moreover, due to their good biocompatibility and biodegradability, TPS-based nanoparticles have emerged as effective nanocarriers for the delivery of bioactive molecules. In this study, we developed a TPS-based biocarrier system for the orally targeted administration of Mn(II) ions and investigated their antidiabetic effects in C57BL/6 mice with HFD/streptozotocin (STZ)-induced T2DM. Mn(II)-loaded TPS-based nanoparticles (MTNPs) were synthesized, in which negatively charged functional groups in protein and uronic acid in TPS conjugates would act as binding sites for Mn(II) ions, which is responsible for the cross-linking reaction of MTNP. The resulting MTNP had a spherical shape and a mean particle size of around 30 nm with a Mn(II) ion content of 2.24 ± 0.13 mg/g. In T2DM mice, we discovered that MTNP treatment significantly lowered blood glucose levels and improved glucose intolerance. Furthermore, the impact of MTNP on the recovery of FINS, the homeostatic index of insulin resistance (HOMA-IR), and the homeostatic index of β-cell (HOMA β-cell) levels was significantly larger (p < 0.05) than TPS alone, demonstrating that Mn(II) ions can enhance TPS's ability to repair HFD/STZ-induced β-cell damage. Mn(II) ions in MTNP not only acted as cofactors to increase the exocytosis of insulin secretory cells by upregulating the expression of Ca(II)/calmodulin-dependent protein kinase II (CaMK II) but also promoted TPS's lipid-lowering effect in T2DM mice by inhibiting glucogenesis and regulating the lipid metabolism. Our findings suggest that Mn(II) ions can be used not only as cross-linkers in the formation of nanoparticulated TPS but also as cofactors in improving the functional role of TPS in regulating the glucose and lipid metabolism, which will provide insights into the development of TPS-based drug delivery systems for the prevention of type 2 diabetes.

Portulaca oleracea L. extract reduces hyperglycemia via PI3k/Akt and AMPK pathways in the skeletal muscles of C57BL/Ksj-db/db mice

Headings ethnopharmacological relevancePortulaca oleracea L. is a succulent annual herb, which has various pharmacological effects including antidiabetic property. However, in vivo the reducing effect of P. oleracea on hyperglycemia and its mechanism of action have not been clarified in a mouse model of type 2 diabetes. Aim of the studyThe effects of Portulaca oleracea L. extract (POE) on hyperglycemia were investigated in an animal model of type 2 diabetes. Materials and methodsC57BL/Ksj-db/db mice were randomly divided into three groups: db/db-control group was fed a standard semi-synthetic diet (AIN-93 G), db/db-RG group was fed AIN-93 G supplemented with rosiglitazone (RG) (0.005%, w/w), and db/db-POE group was fed AIN-93 G supplemented with POE (0.4%, w/w) for 6 weeks. Diabetes-related physical and biochemical indicators and the phosphorylation of components of PI3k/Akt and AMPK pathways were measured. ResultsThe blood glucose and the glycosylated hemoglobin levels (HbA1c) in db/db-POE group were significantly lower than those in db/db-control group. In db/db-POE group, The homeostatic index of insulin resistance (HOMA-IR) decreased significantly, whereas the quantitative insulin sensitivity check index (QUICKI) was higher than those in db/db-control group. POE significantly elicited the phosphorylation of IRS-1Tyr612, AktSer473, and AS160Thr642, and the activation of PI3K in the skeletal muscle of mice. Additionally, POE significantly stimulated the phosphorylation of AMPKThr172, TBC1D1Ser231, and ACCSer79 and elevated the expression of plasma membrane-glucose transporter type 4 (GLUT4). ConclusionsThese results indicate that POE reduces hyperglycemia by improving insulin resistance through the PI3k/Akt and AMPK pathways in the skeletal muscle of C57BL/Ksj-db/db mice.

Retraction: Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice.

[This retracts the article on p. 507 in vol. 10, PMID: 27698958.].

Long-term follow-up of gonadal dysfunction in morbidly obese adolescent boys after bariatric surgery.

Background Elevated body mass index (BMI) is associated with hypogonadism in men but this is not well described in adolescents. The aim is to evaluate gonadal dysfunction and the effects of weight loss after gastric banding in obese adolescent boys. Methods Thirty-seven of 54 boys (age 16.2±1.2 years, mean BMI 48.2 kg/m2) enrolled at the Center for Adolescent Bariatric Surgery at Columbia University Medical Center had low total testosterone for Tanner 5 <350 ng/dL. Sixteen had long-term hormonal data for analysis at baseline (T0), 1 year (T1) and 2 years (T2) post-surgery. T-tests, chi-squared (χ2) tests, correlation and linear mixed models were performed. Results At T0, the hypogonadal group had higher systolic blood pressure (SBP) (75th vs. 57th percentile, p=0.02), fasting insulin (19 vs. 9 μIU/mL, p=0.0008) and homeostatic index of insulin resistance (HOMA-IR) (4.2 vs. 1.9, p=0.009) compared to control group. Total testosterone was negatively correlated with fasting insulin and HOMA-IR. In the long-term analysis, BMI, weight, waist circumference (WC), and % excess weight decreased at T1 and T2 compared to T0. Mean total testosterone at T0, T1 and T2 were 268, 304 and 368 ng/dL, respectively (p=0.07). There was a statistically significant negative correlation between BMI and testosterone after 2 years (r=-0.81, p=0.003). Conclusions Low testosterone levels but unaltered gonadotropins are common in this group and associated with insulin resistance. While a significant increase in testosterone was not found over time, the negative relationship between BMI and testosterone persisted, suggesting there may be an optimal threshold for testosterone production with respect to BMI. Long-term studies are needed.

Nardostachys jatamansi DC Extract Alleviates Insulin Resistance and Regulates Glucose Metabolism in C57BL/KsJ-db/db Mice Through the AMP-Activated Protein Kinase Signaling Pathway.

This study investigated whether Nardostachys jatamansi DC extract (NJE) improved insulin sensitivity and suppressed hepatic glucose production in an animal model of type 2 diabetes. C57BL/KsJ-db/db mice were divided into three dietary groups: regular diet (control), NJE, and rosiglitazone. After 6 weeks of feeding, blood glucose, glycosylated hemoglobin, and plasma insulin levels were significantly lower in NJE than in diabetic control group mice. The oral glucose tolerance test also revealed a positive effect of NJE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in NJE than in diabetic control group mice. NJE markedly lowered the plasma lipid concentration compared to diabetic control group mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and plasma membrane glucose transporter type 4 increased more in NJE compared to diabetic control group mice. NJE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. These findings demonstrate that NJE alleviates hyperglycemia by improving insulin sensitivity and inhibiting gluconeogenesis in the liver.

The association between insulin resistance, metabolic syndrome, and ischemic heart disease among Rumoi residents.

BackgroundIt has widely been proven that metabolic syndrome (MetS) increases the risk of ischemic heart disease (IHD). MetS is confirmed based upon insulin resistance (IR). Our aim of this study is to evaluate the role of MetS and IR in the prediction of IHD incidence.MethodsA total of 404 non‐diabetic participants who underwent 75 g oral glucose tolerance test (75 g OGTT) were enrolled from 2001 to 2009. Risk factors for IHD were measured as well. The homeostatic index of IR (HOMA‐IR) and the homeostatic model assessment beta cell function (HOMA‐β) were calculated according to the homeostasis model assessment. Cox proportional‐hazard regression model was used to estimate hazard ratio (HR). All data were analyzed using SPSS 21 software (IBM, Armonk, NY, USA).ResultsIn our study, the average follow‐up period was 6.7 years. Eighteen subjects of IHD incidence were recorded. After adjusting for age and sex, subjects with IR or hyperinsulinemia had a high risk of IHD, the hazard ratio (95% confidence intervals) for IHD were 4.58 (1.59‐13.15), 4.25 (1.64‐11.91), respectively. The highest hazard ratio was 7.56 (2.27‐25.18) which was found among the subjects with both IR and hyperinsulinemia. In addition, the hazard ratio (95% confidence intervals) of subjects with MetS was 2.80(1.10‐7.09).Conclusions IR and hyperinsulinemia are related to the risk of IHD. IR combined with hyperinsulinemia may be superior to MetS for predicting the IHD incidence.

Beneficial Effects of Pterocarpan-High Soybean Leaf Extract on Metabolic Syndrome in Overweight and Obese Korean Subjects: Randomized Controlled Trial.

Pterocarpans are known to have antifungal and anti-inflammatory properties. However, little is known about the changes in transcriptional profiles in response to a pterocarpan-high soybean leaf extract (PT). Therefore, this study investigated the effects of PT on blood glucose and lipid levels, as well as on the inflammation-related gene expression based on a peripheral blood mononuclear cells (PBMCs) mRNA sequencing analysis in Korean overweight and obese subjects with mild metabolic syndrome. The participants were randomly assigned to two groups and were administered either placebo (starch, 3 g/day) or PT (2 g/day) for 12 weeks. The PT intervention did not change body weight, body fat percentage and body mass index (BMI). However, PT significantly decreased the glycosylated hemoglobin (HbA1c), plasma glucose, free fatty acid, total cholesterol, and non-HDL cholesterol levels after 12 weeks. Furthermore, PT supplementation significantly lowered the homeostatic index of insulin resistance, as well as the plasma levels of inflammatory markers. Finally, the mRNA sequencing analysis revealed that PT downregulated genes related to immune responses. PT supplementation is beneficial for the improvement of metabolic syndrome by altering the fasting blood and plasma glucose, HbA1c, plasma lipid levels and inflammation-related gene expression in PBMCs.

Mulberry (Morus alba L.) Fruit Extract Containing Anthocyanins Improves Glycemic Control and Insulin Sensitivity via Activation of AMP-Activated Protein Kinase in Diabetic C57BL/Ksj-db/db Mice.

The effect of mulberry (Morus alba L.) fruit extract (MFE) on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes was evaluated. C57BL/Ksj-diabetic db/db mice were divided into three groups: diabetic control, rosiglitazone, and MFE groups. Blood glucose, plasma insulin, and intraperitoneal glucose were measured, and an insulin tolerance test was performed after MFE supplementation in db/db mice. In addition, the protein levels of various targets of insulin signaling were measured by western blotting. The blood levels of glucose and HbA1c were significantly lower in the MFE-supplemented group than in the diabetic control group. Moreover, glucose and insulin tolerance tests showed that MFE treatment increased insulin sensitivity. The homeostatic index of insulin resistance significantly decreased in the MFE-supplemented group relative to the diabetic control group. MFE supplementation significantly stimulated the levels of phosphorylated (p)-AMP-activated protein kinase (pAMPK) and p-Akt substrate of 160 kDa (pAS160) and enhanced the level of plasma membrane-glucose transporter 4 (GLUT4) in skeletal muscles. Further, dietary MFE significantly increased pAMPK and decreased the levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. MFE may improve hyperglycemia and insulin sensitivity via activation of AMPK and AS160 in skeletal muscles and inhibition of gluconeogenesis in the liver.

Gynura procumbens extract improves insulin sensitivity and suppresses hepatic gluconeogenesis in C57BL/KsJ-db/db mice.

BACKGROUND/OBJECTIVESThis study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes.MATERIALS/METHODSC57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks.RESULTSMice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver.CONCLUSIONSThese findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

The Protective Effect of a Novel Coumarinic Derivative on Streptozotocin Induced Diabetic Rats

The Protective Effect of a Novel Coumarinic Derivative on Streptozotocin Induced Diabetic Rats Diabetes mellitus (DM) affects more than 415 million persons worldwide. It is one of the most important causative factors of mortality in the developing countries. It was established that Streptozotocin (STZ) is a chemical compound that induces diabetic complications in rats. This study aimed to examine the ability of novel coumarine-caffeic acid derivative: Ethyl-3-(3, 4- dihydroxyphenyl) acrylamido--5-methoxy-1-(4- methoxyphenyl)-10-methyl-8-oxo-1, 8-dihydropyrano [3, 2-f] chromene-2-carboxylate (Compound I) to reduce the diabetic complications induced by STZ.Diabetes was induced in the rats by the injection with STZ (65 mg/Kg b.w). Diabetes was confirmed then we allowed 7 days to stabilize blood glucose level in these rats. Compound I (25 and 50 mg/kg b.w daily for 4 weeks) was injected into diabetic rats. The treated diabetic rats with Compound I had significantly reduced the high blood glucose level, Homeostatic index of insulin resistance (HOMA IR), Triglycerides (TG), Total-Cholesterol (TC), Low Density Lipoprotein-Cholesterol (LDL-c), Very Low Density Lipoprotein- Cholesterol (VLDL-c) and atherogenic index. The treatment with Compound I also resulted in the improvement of the insulin and insulin resistance and significantly increased serum High Density Lipoprotein Cholesterol (HDL-c), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPx) as well as decreased TBARS in the liver of diabetic rats. Compound I showed protective effects against hyperglycemia. It decreases the blood glucose level and improves the lipid profile by scavenging of free radicals and reducing the risk of diabetic complications.

Jicama (Pachyrhizus erosus) extract increases insulin sensitivity and regulates hepatic glucose in C57BL/Ksj-db/db mice.

This study investigated the effect of jicama extract on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes. Male C57BL/Ksj-db/db mice were divided into groups subsequently fed a regular diet (controls), or diet supplemented with jicama extract, and rosiglitazone. After 6 weeks, blood levels of glucose and glycosylated hemoglobin were significantly lower in animals administered the jicama extract than the control group. Additionally, glucose and insulin tolerance tests showed that jicama extract increased insulin sensitivity. The homeostatic index of insulin resistance was lower in the jicama extract-treated group than in the diabetic control group. Administration of jicama extract significantly enhanced the expressions of the phosphorylated AMP-activated protein kinase and Akt substrate of 160 kDa, and plasma membrane glucose transporter type 4 in skeletal muscle. Jicama extract administration also decreased the expressions of glucose 6-phosphatase and phosphoenol pyruvate carboxykinase in the liver. Jicama extract may increases insulin sensitivity and inhibites the gluconeogenesis in the liver.

Padina arborescens Ameliorates Hyperglycemia and Dyslipidemia in C57BL/KsJ-db/db Mice, a Model of Type 2 Diabetes Mellitus.

Recently, there has been a growing interest in alternative therapies and in the therapeutic use of natural products for the treatment of diabetes. Therefore, in this study, we investigated the hypoglycemic and hypolipidemic effects of brown algae, Padina arborescens, in an animal model of type 2 diabetes. For 6 weeks, male C57BL/KsJ-db/db mice were administrated either control diet with no treatment or were treated with rosiglitazone (RG; 0.005%, w/w) or P. arborescens extract (PAE; 0.5%, w/w). At the end of the experimental period, the blood glucose levels, glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the RG and PAE groups compared with the control group. In addition, glucose tolerance was significantly improved in the RG and PAE groups. The homeostatic index of insulin resistance was lower in the RG and PAE groups than the diabetic control group. Also, the total cholesterol, LDL-cholesterol, triglyceride, and free fatty acid levels were lower in the PAE group than in the control group, whereas the HDL-C level was higher in the PAE group. Supplementation with PAE significantly lowered hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, and increased glucokinase activity in the liver. Consequently, these results suggest that PAE may be beneficial in improving insulin resistance, hyperglycemia, and dyslipidemia in type 2 diabetics.

Novel Clinical Evidence of an Association between Homocysteine and Insulin Resistance in Patients with Hypothyroidism or Subclinical Hypothyroidism.

ObjectiveHypothyroidism (HO) can induce significant metabolic dysfunction and increase cardiovascular disease risk. In the present study, we investigated the relationship between homocysteine (Hcy) and insulin resistance (IR) in patients with HO or subclinical hypothyroidism (SHO).MethodsA total of 270 subjects were enrolled. All subjects were divided into the following three groups: HO, SHO and control. Plasma levels of Hcy were measured, and each patient’s homeostatic index of insulin resistance (HOMA-IR) was calculated. Statistical analyses were carried out to evaluate the correlations among groups and to determine the predictors of IR in patients with HO or SHO.ResultsThe HOMA-IR value was significantly higher in the HO group than in the SHO and control groups. Plasma levels of Hcy were markedly increased in the HO group compared with those of the SHO group and controls. In addition, plasma levels of Hcy were positively correlated with the HOMA-IR values in both the HO and SHO groups. Multiple linear regression models showed that plasma levels of Hcy and free thyroxine (FT4) were the only predictors of HOMA-IR in patients with HO or SHO.ConclusionsPlasma levels of Hcy and HOMA-IR were increased in patients with HO or SHO. Our results suggest that HO and SHO may increase the risk for atherogenesis and cardiovascular disease by increased IR. The increased IR induced by hyperhomocysteinemia in patients with HO or SHO may partially explain this adverse effect.

Sargassum coreanum extract alleviates hyperglycemia and improves insulin resistance in db/db diabetic mice.

BACKGROUND/OBJECTIVESThe goal of this study was to examine the effect of Sargassum coreanum extract (SCE) on blood glucose concentration and insulin resistance in C57BL-KsJ-db/db mice.MATERIALS/METHODSFor 6 weeks, male C57BL/KsJ-db/db mice were administrated SCE (0.5%, w/w), and rosiglitazone (0.005%, w/w).RESULTSA supplement of the SCE for 6 weeks induced a significant reduction in blood glucose and glycosylated hemoglobin concentrations, and it improved hyperinsulinemia compared to the diabetic control db/db mice. The glucokinase activity in the hepatic glucose metabolism increased in the SCE-supplemented db/db mice, while phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities in the SCE-supplemented db/db mice were significantly lower than those in the diabetic control db/db mice. The homeostatic index of insulin resistance was lower in the SCE-supplemented db/db mice than in the diabetic control db/db mice.CONCLUSIONSThese results suggest that a supplement of the SCE lowers the blood glucose concentration by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice

To evaluate antidiabetic and anti-inflammatory effects of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-related infertility. Experimental. University laboratory. Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH. Wild-type placebo group; wild-type resveratrol group; ob/ob mice placebo group; ob/ob mice resveratrol group. Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol. Body and reproductive system weight, food intake, fasting blood glucose, plasma insulin and T levels, and Homeostatic Index of Insulin Resistance; interleukin-6 and tumor necrosis factor-α levels in adipose tissue by Western blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles. Plasma insulin and T levels decreased and Homeostatic Index of Insulin Resistance improved in ob/ob mice treated with resveratrol. Interleukin-6 and tumor necrosis factor-α levels were significantly reverted back to near normalcy after resveratrol treatment in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wild-type mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group. Resveratrol administration could exert benefits against loss of ovarian follicles, and these actions may be mediated, at least in part, via anti-inflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to preserve ovarian reserve in conditions associated with obesity. Our results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females.

Smoking in infertile women with polycystic ovary syndrome: baseline validation of self-report and effects on phenotype.

Do women with polycystic ovary syndrome (PCOS) seeking fertility treatment report smoking accurately and does participation in infertility treatment alter smoking? Self-report of smoking in infertile women with PCOS is accurate (based on serum cotinine levels) and smoking is unlikely to change over time with infertility treatment. Women with PCOS have high rates of smoking and it is associated with worse insulin resistance and metabolic dysfunction. Secondary study of smoking history from a large randomized controlled trial of infertility treatments in women with PCOS (N = 626) including a nested case-control study (N = 148) of serum cotinine levels within this cohort to validate self-report of smoking. Women with PCOS, age 18-40, seeking fertility who participated in a multi-center clinical trial testing first-line ovulation induction agents conducted at academic health centers in the USA. Overall, self-report of smoking in the nested case-control study agreed well with smoking status as determined by measure of serum cotinine levels, at 90% or better for each of the groups at baseline (98% of never smokers had cotinine levels <15 ng/ml compared with 90% of past smokers and 6% of current smokers). There were minor changes in smoking status as determined by serum cotinine levels over time, with the greatest change found in the smoking groups (past or current smokers). In the larger cohort, hirsutism scores at baseline were lower in the never smokers compared with past smokers. Total testosterone levels at baseline were also lower in the never smokers compared with current smokers. At end of study follow-up insulin levels and homeostatic index of insulin resistance increased in the current smokers (P < 0.01 for both) compared with baseline and with non-smokers. The chance for ovulation was not associated with smoking status, but live birth rates were increased (non-significantly) in never or past smokers. The limitations include the selection bias involved in our nested case-control study, the possibility of misclassifying exposure to second hand smoke as smoking and our failure to capture self-reported changes in smoking status after enrollment in the trial. Because self-report of smoking is accurate, further testing of smoking status is not necessary in women with PCOS. Because smoking status is unlikely to change during infertility treatment, extra attention should be focused on smoking cessation in current or recent smokers who seek or who are receiving infertility treatment. Sponsored by the Eugene Kennedy Shriver National Institute of Child Health and Human Development of the U.S. National Institutes of Health. ClinicalTrials.gov numbers, NCT00068861 and NCT00719186.

Ishige okamurae ameliorates hyperglycemia and insulin resistance in C57BL/KsJ-db/db mice

We investigated the effect of Ishige okamurae extract on blood glucose level and insulin resistance in C57BL/-KsJ-db/db mice. We administered a standard AIN-93G diet with or without IOE to the animals for 6 weeks. After 6 weeks, blood glucose level was improved and blood glycosylated hemoglobin levels were lowered in sample group mice as compared to those in the diabetic control group mice. Hyperinsulinemia was reduced in the I. okamurae extract group mice with type 2 diabetes. With regard to hepatic glucose metabolic enzyme activities, glucokinase activity was enhanced in the IOE group mice, while glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the IOE group mice were significantly lowered than those in the diabetic control group mice. In addition, the hepatic glycogen content was elevated in the IOE group as compared to that in the diabetic control group. The homeostatic index of insulin resistance was lower in the I. okamurae extract group mice than in the diabetic control group mice. These results suggest that a dietary supplement of I. okamurae extract lowers the blood glucose level by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.

Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Hyperandrogenemia, insulin resistance, and dyslipidemia demonstrate familial aggregation in the female first-degree relatives of women with polycystic ovary syndrome (PCOS), suggesting that these defects are heritable. Hyperandrogenemia also appears to be the male reproductive phenotype. We performed this study to test the hypothesis that brothers of women with PCOS have metabolic defects similar to those of their proband sisters. This was a prospective case-control study performed at four academic medical centers in the U.S. Fasting blood was obtained from 196 non-Hispanic white brothers of women with PCOS and 169 control men of age, BMI, and ethnicity comparable to those of brothers. A separate analysis was performed by study site to assess potential regional variations in metabolic parameters. Overall, brothers of women with PCOS had significantly higher total (P = 0.001) and LDL cholesterol (P = 0.01) as well as triglyceride levels (P = 0.01) compared with control men, although there were regional variations in these differences. There were significant positive correlations between brothers and their sisters with PCOS for total (rho = 0.2, P = 0.009) and LDL cholesterol (rho = 0.3, P = 0.001) and triglyceride (rho = 0.2, P = 0.05) levels. Brothers also had significantly higher fasting insulin levels and homeostatic index of insulin resistance (P = 0.02 for both comparisons) compared with control men. Brothers of women with PCOS have dyslipidemia as well as evidence for insulin resistance similar to that of their proband sisters with PCOS. These findings are consistent with the hypothesis that some metabolic abnormalities in PCOS are heritable and are not sex specific.