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Insulin resistance - Top 30 Publications

MECHANISTIC INSIGHTS INTO OSTEOPOROSIS IN PATIENTS WITH LIPODYSTROPHY AND REVIEW OF THE LITERATURE.

To demonstrate the underlying pathogenesis of osteoporosis occurring in patients with lipodystrophy.

Determinants of coronary flow reserve in non-diabetic patients with chest pain without myocardial perfusion defects.

Microvascular dysfunction could be responsible for chest pain in patients without myocardial perfusion defects. We evaluated microvascular function using ultrasound-assessed coronary flow reserve (CFR) in patients with chest pain and normal myocardial perfusion scintigram. Secondly, we investigated association between cardiovascular parameters and decreased CFR in a sex specific manner.

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes.

Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women.

Long-term consequences of obesity on female fertility and the health of the offspring.

Obesity has reached near epidemic levels among reproductive age women with a myriad of consequences. Obesity adversely affects the maternal milieu by creating conditions that decrease fertility and increase the risk of gestational diabetes, hypertensive disease in pregnancy, fetal growth abnormalities and congenital anomalies. The effects of obesity are not limited to pregnancy. Indeed, beyond the immediate postpartum period, obese women maintain a higher prevalence of insulin resistance and cardiovascular disease. In this article, we will review the pathophysiology underlying the effects of obesity on fertility, pregnancy outcome and health status of offspring. The purpose of this review is to outline proposed models responsible for the short-term and long-term consequences of obesity on fertility and offspring development, and identify knowledge gaps where additional research is needed.

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels.

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high‑fat diet‑mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon‑like peptide‑1 and ‑2, peptide YY, glucose‑dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high‑fat diet‑fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance.

Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia.

Previous studies have investigated the lower embryo implantation rates in women with polycystic ovary syndrome, obesity and type 2 diabetes, and specifically the association between the abnormal oocyte and embryo and hyperinsulinemia. The importance of hyperinsulinemia on maternal endometrium receptivity remains to be elucidated. The present study used a hyperinsulinemic mouse model to determine whether hyperinsulinemia may affect endometrial receptivity. An insulin intervention mouse model was first established. The serum levels of insulin, progesterone and estradiol were subsequently detected by ELISA assay analysis. The number of implantation sites was recorded using Trypan blue dye and the morphology of mice uteri was investigated using hematoxylin and eosin staining. The expression levels of molecular markers associated with endometrial receptivity were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry analyses. Finally, the importance of mechanistic target of rapamycin (mTOR) expression following insulin treatment was determined. Mice treated with insulin developed insulin resistance and hyperinsulinemia. The number of implantation sites following insulin treatment did not differ between the control and insulin‑treated groups. Additionally, no significant morphological alterations in mice uteri between control and insulin‑treated groups were observed. However, the expression levels of estrogen receptor (Esr) 1, Esr2, progesterone receptor and homeobox A10 associated with endometrial receptivity, were imbalanced during endometrium receptivity when maternal hyperinsulinemia was induced. Western blot analysis revealed that expression levels of endometrial phosphorylated (p)‑mTOR and p‑ribosomal protein S6 kinase β‑1 were significantly greater in the insulin‑treated group. These results demonstrated that although an embryo may implant into endometrium, mice endometrium receptivity in early pregnancy may be impaired by maternal hyperinsulinemia. In addition, mTOR signaling may be involved in this process. The present study provides preliminary results demonstrating that female reproduction may be compromised during hyperinsulinemia, which requires further investigation in future studies.

Pioglitazone ameliorates Aβ42 deposition in rats with diet-induced insulin resistance associated with AKT/GSK3β activation.

Pioglitazone may have potential benefits as an alternative therapeutic treatment for patients with Alzheimer's disease (AD), particularly in individuals that also have comorbid diabetes; however, the mechanisms of action remain unclear. The present study aimed to explore the effects of pioglitazone on amyloid β, isoform 42 (Aβ42) deposition in rats with diet‑induced insulin resistance (IR). Diet‑induced IR model rats were established in the presence or absence of pioglitazone. Plasma glucose and insulin levels, and cerebrospinal fluid insulin levels were measured; in addition, hippocampal tissues were collected for immunohistochemical analysis of Aβ42 expression. The levels of insulin‑degrading enzyme (IDE) and peroxisome proliferator‑activated receptor γ (PPARγ) mRNA and protein expression were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, the activation of glycogen synthase kinase 3β (GSK3β) induced by phosphatidylinositol 3‑kinase (PI3K) /protein kinase B (AKT) signaling was detected by western blotting. Results from the present study demonstrated that pioglitazone may enhance peripheral and brain insulin sensitivity in diet‑induced IR model rats. Treatment with pioglitazone ameliorated Aβ42 deposition in the hippocampus by increasing IDE and PPARγ expression. Notably, activation of the PI3K/AKT/GSK3β pathway was also demonstrated to serve a role in pioglitazone‑induced Aβ42 degradation, which was abrogated by the PPARγ antagonist GW9662. Results from the present study indicated that pioglitazone may improve insulin sensitivity and ameliorate Aβ42 accumulation in rats with diet‑induced IR by regulating AKT/GSK3β activation, suggesting that pioglitazone may be a promising drug for AD treatment.

A New Treatment Strategy for Parkinson's Disease Through the Gut-Brain Axis: The Glucagon-like Peptide-1 Receptor Pathway.

Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases. Glucagon-like peptide-1 (GLP-1)-based anti-diabetic drugs have drawn particular attention as an effectual new strategy to not only regulate blood glucose but also to decrease body weight by reducing appetite, which implies that GLP-1 could affect the gut-brain axis in normal and pathological conditions. The neurotrophic and neuroprotective effects of GLP-1 receptor (R) stimulation have been characterized in numerous in vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl peptidase 4 inhibitors. Recently, the first open label clinical study of exenatide, a long acting GLP-1 agonist, in the treatment of PD showed long-lasting improvements in motor and cognitive function. Several double blind clinical trials of GLP-1R agonists including exenatide in PD and other neurodegenerative disease are already underway or are about to be initiated. Herein, we review the physiological role of the GLP-1R pathway in the gut-brain axis and the therapeutic strategy of GLP-1R stimulation for the treatment of neurodegenerative diseases focused on PD, for which age is the major risk factor.

Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance.

Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.

MicroRNA 21 is up-regulated in adipose tissue of obese diabetic subjects.

We investigated miR21 expression in omental (OAT) and subcutaneous adipose tissue (SAT) from 16 obese subjects undergoing bariatric surgery. Patients were divided into two age- and BMI-matched groups according to the presence of type 2 diabetes (T2D). miR21 was not differently expressed in OAT and SAT. However, miR21 expression was two folds greater in adipose tissue in patients with T2D. Accordingly, in primary cultures of adipocytes from non diabetic overweight subjects, miR21 expression increased after 24-h exposure to high glucose and insulin. In conclusion, miR21 appears linked to insulin-resistance deterioration within its pathophysiologic progression from obesity to T2D.

Neuronal functions of FOXO/DAF-16.

The FOXO family of transcription factors plays a conserved role in longevity and tissue homeostasis across species. In the mammalian nervous system, emerging evidence has implicated FOXOs in cognitive performance, stem cell maintenance, regeneration, and protection against stress. Much of what we know about neuronal functions of FOXO emerged from recent studies in C. elegans. Similar to mammalian FOXO, the worm FOXO ortholog, called DAF-16, regulates learning and memory, regeneration, and stress resistance in neurons. Here, we discuss the current state of our knowledge of FOXO's functions in neurons in mammals and invertebrates, and highlight areas where our understanding is limited. Defining the function of FOXO factors in the healthy, aged, and diseased brain may have important implications for improving healthspan and treating neurodegenerative disease.

Effect of genetic variants and traits related to glucose metabolism and their interaction with obesity on breast and colorectal cancer risk among postmenopausal women.

Impaired glucose metabolism-related genetic variants and traits likely interact with obesity and related lifestyle factors, influencing postmenopausal breast and colorectal cancer (CRC), but their interconnected pathways are not fully understood. By stratifying via obesity and lifestyles, we partitioned the total effect of glucose metabolism genetic variants on cancer risk into two putative mechanisms: 1) indirect (risk-associated glucose metabolism genetic variants mediated by glucose metabolism traits) and 2) direct (risk-associated glucose metabolism genetic variants through pathways other than glucose metabolism traits) effects.

Serum irisin levels correlated to peritoneal dialysis adequacy in nondiabetic peritoneal dialysis patients.

Irisin is a recently discovered myokine thought to be involved in multiple metabolism abnormalities in most dialysis patients. However, the myokine has not been thoroughly studied in peritoneal dialysis. This study aimed to evaluate serum irisin levels and establish their relation to dialysis adequacy, insulin resistance, and bone metabolism status in patients on peritoneal dialysis.

Fructose, Glucocorticoids and Adipose Tissue: Implications for the Metabolic Syndrome.

The modern Western society lifestyle is characterized by a hyperenergetic, high sugar containing food intake. Sugar intake increased dramatically during the last few decades, due to the excessive consumption of high-sugar drinks and high-fructose corn syrup. Current evidence suggests that high fructose intake when combined with overeating and adiposity promotes adverse metabolic health effects including dyslipidemia, insulin resistance, type II diabetes, and inflammation. Similarly, elevated glucocorticoid levels, especially the enhanced generation of active glucocorticoids in the adipose tissue due to increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, have been associated with metabolic diseases. Moreover, recent evidence suggests that fructose stimulates the 11β-HSD1-mediated glucocorticoid activation by enhancing the availability of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11β-HSD1 expression and activity, thereby promoting the adipogenic effects of glucocorticoids. This article aims to highlight the interconnections between overwhelmed fructose metabolism, intracellular glucocorticoid activation in adipose tissue, and their metabolic effects on the progression of the metabolic syndrome.

Diagnostic accuracy of serum alanine aminotransferase as biomarker for nonalcoholic fatty liver disease and insulin resistance in healthy subjects, using 3T MR spectroscopy.

Recognition of the close relationship of nonalcoholic fatty liver disease (NAFLD) with diabetes mellitus 2, obesity, metabolic syndrome, and cardiovascular disease has stimulated growing interest in NAFLD as a public health problem. Serum alanine aminotransferase (ALT) has been proposed as a marker of NAFLD, but levels are within the range currently considered "normal" in a large proportion of NAFLD subjects.The aim of the study was to determine the diagnostic accuracy of serum ALT for identifying individuals with NAFLD, using 3-Tesla (T) magnetic resonance spectroscopy (H-MRS).A cross-sectional study was conducted in 129 healthy subjects. Liver triglyceride content was quantified by H-MRS. NAFLD was defined as liver triglyceride content greater than 5.56%.Liver triglyceride content was >5.56% in 79 participants (NAFLD) and lower in the remaining 50 (normal). Serum ALT levels correlated positively with liver triglyceride content (r = 0.58, P < .001), Homeostatic Model Assessment for Insulin Resistance (r = 0.32, P < .01), and fasting insulin (r = 0.31, P < .01), and inversely correlated with adiponectin (r = 0.35, P < .01) and high-density lipoprotein cholesterol (r = 0.32, P < .01). Regression analysis showed that serum ALT was the best predictor of NAFLD (P < .01). Optimal serum ALT cut-off to predict NAFLD was 23 IU/L (area under receiver-operating characteristic curve: 0.93; sensitivity: 0.94; specificity: 0.72).This study shows that serum ALT is a sensitive and accurate biomarker of NAFLD if the "normal" ALT value is revised and established at a lower level. An ALT threshold of 23 IU/L identified 94% of individuals with NAFLD in the present series, using 3-T H-MRS for liver triglyceride quantification.

25(OH)D Levels in Relation to Gender, Overweight, Insulin Resistance, and Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in Support of Preventive Health Care Programs.

In recent years, the welfare of workers and the prevention of chronic disabling diseases has become a topic of great interest. This study investigates serum levels of total 25-hydroxyvitamin D (25(OH)D) in a cohort of overweight-obese and insulin-resistant northern Italian indoor workers in apparent good health followed a nutritional education program.

Crosstalk Between Bone and Fat Tissue: Associations Between Vitamin D, Osteocalcin, Adipokines, and Markers of Glucose Metabolism Among Adolescents.

This study aimed to investigate the relationship between 25-hydroxyvitamin D (25(OH)D), osteocalcin, markers of glucose metabolism, and obesity-related parameters among adolescents.

Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases.

Insulin and leptin resistance are important risk factors for non-alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the effects of turmeric on NAFLD. The aim of this study was to investigate the effects of turmeric supplementation on glycemic status and serum leptin levels in patients with NAFLD.

The Increased Risk of Metabolic Syndrome in Patients with Vitiligo.

Inflammatory and immune processes can be triggered in vitiligo due to decreased number of the melanocytes and their anti-inflammatory effects. Because of systemic nature of vitiligo, metabolic abnormalities such as insulin resistance and lipid profile disturbances as well as skin involvement may be observed in vitiligo.

Diabetes mellitus caused by secondary hemochromatosis after multiple blood transfusions in 2 patients with severe aplastic anemia.

Hemochromatosis is an inherited or secondary disorder caused by excessive iron storage leading to multiple organ damage. We describe 2 patients with diabetes mellitus caused by hemochromatosis secondary to multiple blood transfusions due to severe aplastic anemia. Subject 1, who was diagnosed with severe aplastic anemia at 15 years of age, received multiple red blood cell transfusions before he underwent autologous peripheral blood stem cell transplantation (PBSCT) at 22 years of age. At 21 years of age, hyperglycemia was detected with increased hemoglobin A1c and serum ferritin levels, 9.7% and 12,910 ng/mL (normal range, 20-320 ng/mL), respectively. The 24-hour urine C-peptide level was normal with negative antiglutamic acid decarboxylase antibody. Subsequently, metformin and an iron-chelating agent were administered. However, an intensive insulin regimen was necessary 2 years after the onset of diabetes. Subject 2, who was diagnosed with severe aplastic anemia at 2 years of age, received multiple blood transfusions until she underwent haploidentical PBSCT at 13 years of age. At 11 years of age, she developed diabetes mellitus with a high serum ferritin level (12,559.8 ng/mL). She is currently 18 years old and has been treated with an intensive insulin regimen and estrogen/progesterone replacement therapy because of hypogonadotropic hypogonadism. It is presumed that the loss of insulin secretory capacity and insulin resistance played a role in the pathogenesis of diabetes mellitus due to hemochromatosis in these cases.

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP.

Evaluation of common variants in MG53 and the risk of type 2 diabetes and insulin resistance in Han Chinese.

Abnormally increased skeletal-muscle-specific E3 ubiquitin ligase (MG53) is associated with the inhibition of insulin signalling and insulin resistance (IR) in animal models. Four community-based studies of Han Chinese populations were included in this study to test the association of variants of MG53 and type 2 diabetes (T2D). The results showed that rs7186832 and rs12929077 in MG53 were significantly associated with T2D and impaired fasting glucose (IFG) of females in the discovery-stage case-control study and cohort study respectively of rural population but not in the replication sample of urban population. In rural population, the fasting insulin (mU/L) of the subjects with AA, AG and GG genotypes in rs12929077 were 8.70 ± 8.05, 10.71 ± 11.16 and 13.41 ± 14.26, respectively, and increased linearly in T2D cases without medication treatment (P = 0.04). This variant was significantly associated with HOMA-IR (P = 0.020) and HOMA-IS (P = 0.023). In individuals with IFG, the insulin and HOMA-IR of AG carriers were significantly higher than those of AA carriers. In urban population, after glucose loading, there were significant differences in the 30-min glucose, the area under the curve (AUC) of 30-min glucose and the AUC of 120-min glucose according to the genotypes of rs7186832 and rs12929077 in males but not females. Our findings suggest that MG53 variants might confer risk susceptibility to the development of T2D of females and IR particularly in rural population.

The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System.

Immune cells not only affect tissue homeostasis at the site of inflammation but also exert systemic effects contributing to multiple chronic conditions. Recent evidence clearly supports an altered T helper 17/regulatory T cell (Th17/Treg) balance leading to the development and progression of inflammatory diseases that not only affect the gastrointestinal tract but also have whole-body manifestations, including insulin resistance. Epigenetic mechanisms are amenable to both environmental and circulating factors and contribute to determining the T cell landscape. The recently identified participation of the gut microbiota in the remodeling of the epigenome of immune cells has triggered a paradigm shift in our understanding of the etiology of various inflammatory diseases and opened new paths toward therapeutic strategies. In this review, we provide an overview of the contribution of the Th17/Treg balance in the development and progression of inflammatory bowel diseases and metabolic diseases. We discuss the involvement of epigenetic mechanisms in the regulation of T cell function in the particular context of dysbiosis. Finally, we examine the potential for nutritional interventions affecting the gut microbiota to reshape the T cell epigenome and address the inflammatory component of various diseases.

Superior Effects of Eccentric to Concentric Knee Extensor Resistance Training on Physical Fitness, Insulin Sensitivity and Lipid Profiles of Elderly Men.

It has been reported that eccentric training of knee extensors is effective for improving blood insulin sensitivity and lipid profiles to a greater extent than concentric training in young women. However, it is not known whether this is also the case for elderly individuals. Thus, the present study tested the hypothesis that eccentric training of the knee extensors would improve physical function and health parameters (e.g., blood lipid profiles) of older adults better than concentric training. Healthy elderly men (60-76 years) were assigned to either eccentric training or concentric training group (n = 13/group), and performed 30-60 eccentric or concentric contractions of knee extensors once a week. The intensity was progressively increased over 12 weeks from 10 to 100% of maximal concentric strength for eccentric training and from 50 to 100% for concentric training. Outcome measures were taken before and 4 days after the training period. The results showed that no sings of muscle damage were observed after any sessions. Functional physical fitness (e.g., 30-s chair stand) and maximal concentric contraction strength of the knee extensors increased greater (P ≤ 0.05) after eccentric training than concentric training. Homeostasis model assessment, oral glucose tolerance test and whole blood glycosylated hemoglobin showed improvement of insulin sensitivity only after eccentric training (P ≤ 0.05). Greater (P ≤ 0.05) decreases in fasting triacylglycerols, total, and low-density lipoprotein cholesterols were evident after eccentric training than concentric training, and high-density lipoprotein cholesterols increased only after eccentric training. These results support the hypothesis and suggest that it is better to focus on eccentric contractions in exercise medicine.

Parathyroidectomy Decreases Insulin Resistance Index in Patients with Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) has been considered a cause of insulin resistance (IR) and impaired glucose metabolism. However, there are conflicting results related with the recovery of insulin resistance in patients with PHPT following curative parathyroidectomy. Our aim is to evaluate the effects of curative parathyroidectomy on IR in patients with PHPT. This is a prospective interventional study. Twenty-one consecutive patients with symptomatic PHPT were included into the study. All patients underwent parathyroidectomy. Fasting serum glucose, calcium, phosphorous, parathormone, plasma insulin, and vitamin D levels were measured both at baseline and 2 months after parathyroidectomy. Insulin resistance was calculated by homeostasis of model assessment-insulin resistance (HOMA-IR). Two months after curative parathyroidectomy, serum levels of calcium (p = 0.001), PTH (p < 0.001), insulin (p = 0.003), and HOMA-IR (p = 0.003) decreased, while phosphorous levels increased (p = 0.001). During this period, no changes were observed at vitamin D and glucose levels. We concluded that curative parathyroidectomy decreases HOMA-IR index in patients with PHPT. Studies with larger population and longer follow-up period are required to confirm our results.

Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance.

Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT (-/-) mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT (-/-) mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance. Treatment of wild type mice with paroxetine, a chemical inhibitor of SERT, also resulted in Cyp19a1 suppression, decreased circulating 17β-estradiol levels, abnormal fat accumulation, and glucose intolerance. Such effects were not observed in paroxetine-treated SERT (-/-) mice. Conversely, pregnant SERT (-/-) mice displayed normalized estrogen levels, markedly reduced fat accumulation, and improved glucose tolerance, which can be eliminated by an antagonist of estrogen receptor α (ERα). Together, these findings support that estrogen suppression is involved in SERT deficiency-induced obesity and glucose intolerance, and suggest approaches to restore 17β-estradiol levels as a novel treatment option for SERT deficiency associated obesity and metabolic abnormalities.

The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology.

Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD.

Zinc alpha-2 glycoprotein is overproduced in Cushing's syndrome.

Cushing syndrome (CS), an endogenous hypercortisolemic condition with increased cardiometabolic morbidity, leads to development of abdominal obesity, insulin resistance, diabetes and proatherogenic dyslipidemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized lipolytic adipokine implicated in regulation of adipose tissue metabolism and fat distribution. In vitro and animal studies suggest that glucocorticoids interact with ZAG secretion and action. To assess the relationship between ZAG and glucocorticoids in a human model of hypercortisolism, circulating ZAG levels were tested in patients with CS and its counterpart controls.

Effect of laparoscopic sleeve gastrectomy on sex hormone in male severe obesity.

To investigate the effect of laparoscopic sleeve gastrectomy(LSG) on sex hormone in male patients with severe obesity.

Increased CD19+CD24+CD27+ B regulatory cells are associated with insulin resistance in patients with type I Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is characterized by dysregulated immune responses and is commonly associated with insulin resistance. However, the mechanism of insulin resistance in HT remains to be fully elucidated. The aim of the present study was to investigate the correlation between the percentage of B regulatory lymphocytes (Bregs) and insulin resistance in patients with HT but with normal thyroid function (type I). A total of 59 patients with type I HT and 38 healthy volunteers were enrolled in the study. An oral glucose tolerance test was performed to measure insulin secretion and assess β‑cell functions. Flow cytometry was performed to examine the percentages of lymphocyte populations. The patients with HT exhibited normal fasting and postprandial glucose and fasting insulin secretion, but increased secretion of early‑phase and total insulin. The patients with HT also had insufficient β‑cell compensation for insulin resistance, indicated by a reduced disposition index, in the fasting state. An elevation in the percentage of CD19+CD24+CD27+ Bregs was also observed, which correlated positively with insulin secretion and insulin resistance in the fasting state. The patients with type I HT had postprandial insulin resistance and insufficient β‑cell compensation for fasting insulin resistance. Therefore, the increase in CD19+CD24+CD27+ Bregs was closely associated with fasting insulin secretion. These results provide novel insight into the mechanism of insulin resistance in HT.