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Hyperinsulinemia - Top 30 Publications

Association of polycystic ovary syndrome with metabolic syndrome and gestational diabetes: Aggravated complication of pregnancy.

Polycystic ovary syndrome (PCOS) affects 5-20% of the reproductive age women globally. PCOS is diagnosed by the presence of hyperandrogenism, oligo-anovulation, and polycystic morphology of at least one ovary. Insulin resistance (IR), hyperinsulinemia and associated metabolic abnormalities including metabolic syndrome play a significant role in the development of PCOS. The chances of developing MS in PCOS women was shown to increase by almost 14-fold in patients with increasing body mass index. Even in the absence of overt obesity, a preferential deposition of intra-abdominal fat is noted in PCOS women and this intra-abdominal fat leads to impaired insulin action and functional IR and hyperandrogenism. Functional ovarian hyperandrogenism of ovaries was suggested to be a consequence of IR, which activates androgen synthesizing enzyme, cytochrome p450-c17α-hydroxylase, in ovarian theca cells and causes elevated oxidative stress accompanied by lower antioxidant status in ovaries, which contribute to PCOS pathogenesis. The elevated levels of luteinizing hormone that accompany the early stages of hyperandrogenemia, accelerate ovarian functional deterioration, which is further aggravated by hyperinsulinemia, in PCOS women. The risk of developing gestational diabetes in PCOS women is approximately three times greater, as compared to non-PCOS women, due to IR and hyperinsulinemia. Typical insulin-sensitizing drugs such as metformin, have been used to curtail IR and hyperinsulinemia in pregnant PCOS women, with varying results indicating the complexity of the disease and the need for better controlled studies and additional efforts for PCOS-specific drug discovery.

Clinical practice guidelines for congenital hyperinsulinism.

Congenital hyperinsulinism is a rare condition, and following recent advances in diagnosis and treatment, it was considered necessary to formulate evidence-based clinical practice guidelines reflecting the most recent progress, to guide the practice of neonatologists, pediatric endocrinologists, general pediatricians, and pediatric surgeons. These guidelines cover a range of aspects, including general features of congenital hyperinsulinism, diagnostic criteria and tools for diagnosis, first- and second-line medical treatment, criteria for and details of surgical treatment, and future perspectives. These guidelines were generated as a collaborative effort between The Japanese Society for Pediatric Endocrinology and The Japanese Society of Pediatric Surgeons, and followed the official procedures of guideline generation to identify important clinical questions, perform a systematic literature review (April 2016), assess the evidence level of each paper, formulate the guidelines, and obtain public comments.

Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

Novel PET tracer (68)Ga-DOTATATE PET/CT can be alternative imaging method in patients with insulinomas.

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. The diagnosis of insulinoma is established by demonstrating inappropriately high serum insulin concentrations during a spontaneous or induced episode of hypoglycaemia. Most of the insulinomas are islet-cell tumors. They are often small (less than 2 cm), benign, and difficult to localize with current imaging techniques. The non-invasive procedures such as transabdominal ultrasonography, spiral computed tomography (CT), magnetic resonance imaging (MRI), 111-In-pentetreotide imaging, fluorine-18-L-dihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) and invasive procedures such as endoscopic ultrasonography or a selective arterial calcium stimulation test (SACST) with hepatic venous sampling can be used to show insulinomas. In this case report we used novel PET tracer (68)Ga-DOTATATE PET/CT for three patients with insulinoma. All patients' insulinomas were shown clearly with (68)Ga-DOTATATE PET/CT. (68)Gallium-DOTATATE PET/CT imaging may be a useful and non-invasive imaging technique to localized insulinomas preoperatively.

The Role of Vascular Endothelial Growth Factor-B in Metabolic Homeostasis: Current Evidence.

It has been shown that adipose tissue and skeletal muscles of lean individuals respond to meal-induced hyperinsulinemia by increases in perfusion, the effect not observed in patients with metabolic syndrome. In conditions of hyperglycaemia and hypertriglyceridemia, this insufficient vascularization leads to the liberation of reactive oxygen species, and disruption of nitric oxide synthesis and endothelial signalling responsible for the uptake of circulating fatty acids, whose accumulation in skeletal muscles and adipose tissue is widely associated with impairment of insulin signalling. While the angiogenic role of VEGF-A and its increased circulating concentrations in obesity have been widely confirmed, the data related to the metabolic role of VEGF-B are diverse. However, recent discoveries indicate that this growth factor may be a promising therapeutic agent in patients with metabolic syndrome. Preclinical studies agree over two crucial metabolic effects of VEGF-B: a) regulation of fatty acids uptake and b) regulation of tissue perfusion via activation of VEGF-A/VEGFR2 pathway. While in some preclinical high-fat diet studies VEGF-B overexpression reverted glucose intolerance and stimulated fat burning, in others it furtherly promoted accumulation of lipids and lipotoxicity. Data from clinical studies point out the changes in circulating or tissue expression levels of VEGF-B in obese versus lean patients. Potentially beneficial effects of VEGF-B, achieved through enhanced blood flow (increased availability of insulin and glucose uptake in target organs) and decreased fatty acids uptake (prevention of lipotoxicity and improved insulin signalling), and its safety for clinical use, remain to be clarified through future translational research.

Relationship Between β-cell Response and Insulin Sensitivity in Horses based on the Oral Sugar Test and the Euglycemic Hyperinsulinemic Clamp.

A hyperbolic relationship between β-cell response and insulin sensitivity (IS) has been described in several species including rodents, dogs, and humans. This relationship has not been elucidated in the horse.

Expression of epidermal growth factor receptor in patients with insulin resistance and seborrheic keratomas.

to study the expression of epidermal growth factor receptor (EGFR) in patients with seborrheic keratomas (SK) and insulin resistance (type 2 diabetes mellitus (DM2)) and in those without concomitant carbohydrate metabolic disturbances.

The pathogenesis and treatment of polycystic ovary syndrome: What's new?

Polycystic ovary syndrome (PCOS) is currently the leading cause of menstrual complications in women. It is characterized by clinical and/or biochemical hyperandrogenism, ovulation abnormalities and the presence of enlarged and/or polycystic ovaries in ultrasound images (12 or more small bubbles located circumferentially and/or ovarian volume > 10 mL). It is often comorbid with hyperinsulinemia, dyslipidemia, overweight or obesity, and is a risk factor for the development of diabetes and cardiovascular diseases (CVDs). The treatment of patients with PCOS depends on the prevailing symptoms. The aim of this paper is to present the etiopathogenesis, clinical and biochemical implications, and non-pharmacological and pharmacological treatment options - those approved by worldwide scientific organizations as well as new therapies whose initial results are encouraging enough to prompt researchers to explore them further.

Chemoprotective effects of butanol fraction of Buchholzia Coriacea ( Capparidaceae ) against Type 2 Diabetes and Oxidative Stress in male Wistar rats.

Recent studies have shown that Type 2 diabetes (T2D) in rats can result through a synergy that link obesity to insulin resistance and β-cell dysfunction. This present study achieved T2D via high fructose (20%(w/v), p.o.), streptozotocin single dose (40 mg/kg, i.p.) (HFSTZ) in rats. Also, chemoprotective potential of butanol fraction of buchholzia coriacea (BFBC) was demonstrated. Control normal and diabetic untreated (HFSTZ-induced T2D) rats received carboxymethyl cellulose (1 mg/kg, p.o.). Diabetic rats received intragastric BFBC (20, 200, 400 mg/kg), glibenclamide (0.07 mg/kg), and BFBC (200mg/kg) plus glibenclamide treatments respectively. 2,2-Diphenyl-1-picrylhydrazyl, nitric oxide radical, hydroxyl radical scavenging activities and α-amylase inhibition were assessed. After two weeks of treatments, blood glucose levels, lipid profiles, renal and liver function, serum insulin as well as in vivo oxidative stress biomarkers were assessed. BFBC shows highest antioxidants and α-amylase inhibitory activities in vitro HFSTZ-induced T2D produced hyperglycemia (p< 0.05 - 0.001; F = 5.26 - 26.47), serum hyperinsulinaemia (6-folds) plus elevated lipid peroxidation levels. Similarly, there were altered lipid profiles, liver and renal biomarker enzymes plus weight loss. BFBC administration alone or in combination with glibenclamide reversed T2D symptomatologies in treated animals, and improved body weights against control diabetic rats. In vivo antioxidant activities also improved while histological sections in treated rats show reduced tissue damage in pancreas, kidneys, liver and heart respectively. Oleic, stearic, 2-methyl-pyrrolidine-2-carboxylic and n-hexadecanoic acids were present in BFBC in large quantities given gas chromatography-mass spectrometry analysis. Overall, data from this study suggest chemoprotective potentials of BFBC against HFSTZ-induced T2D rats.

Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade.

Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3 mg/kg/d oral gavage) from the age of 8 to 16 weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF) -α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obesity, hyperglycemia, hyperinsulinemia and diastolic dysfunction along with cardiac hypertrophy and fibrosis. AZL treatment lowered blood pressure, fasting blood glucose and reduced peak plasma glucose during an oral glucose tolerance test. AZL-3 treatment resulted in a significant decrease in the expression of cytokines, oxidative DNA damage and cardiac dysfunction. Moreover, AZL-3 treatment significantly abrogated the downregulation of ACE-2 and Mas R protein levels in db/db mice. Furthermore, AZL treatment significantly reduced cardiac fibrosis, hypertrophy and their marker molecules (osteopontin, CTGF, TGF-β1 and ANP). Short-term treatment with AZL-3 reversed abnormal cardiac structural remodeling and partially improved glucose metabolism in db/db mice by modulating the ACE-2/ANG 1-7/Mas R pathway.

Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia and brain damage. Therapeutic strategies to avoid near total pancreatectomy in patients who are unresponsive to maximum doses of diazoxide and octreotide remain to be identified, although sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used successfully to treat diffuse type CHI.

Unfolding Link between Diabetes and Cancer.

A growing body of evidence has shown that type 2 diabetes is associated with increased risks of total cancer death and total cancer incidence including cancers of the liver, endometrium, pancreas, kidney, colorectum, bladder, and breast (1) . Of interest, the risk of prostate cancer is significantly decreased. Although the majority of the studies on this topic have been conducted in Western countries, those risk ratios (RRs) of all-cancer mortality and incidence across all cancer types are reportedly even higher in Asians (Table 1) (2) . Type 2 diabetes is characterized by hyperglycemia secondary to insulin resistance, and compensatory hyperinsulinemia. This article is protected by copyright. All rights reserved.

Gestational weight gain in obese pregnancy: impact on maternal and foetal metabolic parameters and birthweight.

The aim of this prospective, observational study was to investigate the impact of gestational weight gain (GWG) among euglycaemic obese pregnant women on maternal and foetal metabolic parameters and neonatal outcome. Total GWG was recorded for 101 obese, non-diabetic women with a singleton pregnancy. At 28 weeks of gestation, fasting maternal blood samples were analysed for glucose, insulin, c-peptide and lipids. Cord bloods were collected at delivery for analysis of glucose, c-peptide and lipids. GWG (mean ± SD =10.9 ± 5.5 kg) was greatest among those of younger age and lower body mass index and 58% of women exceeded the Institute of Medicine GWG recommendations of 5-9 kg for obese pregnancy. GWG was significantly positively associated with increased risk of birthweight >4 kg, cord c-peptide levels and inversely associated with cord total cholesterol. This study identified that higher GWG in obese pregnancy may increase the risk of macrosomia and neonatal hyperinsulinaemia, within a euglycaemic maternal cohort. Impact statement Excess gestational weight gain (GWG) and maternal obesity frequently co-occur with adverse consequences for maternal and neonatal health; however, little is known of the underlying biological pathways which may be affected to contribute to adverse outcomes. Greater understanding of the biological mechanisms involved may help guide future studies to develop targeted interventions for more effective clinical outcomes. This study identified that higher GWG among obese pregnant women resulted in foetal hyperinsulinaemia even in the absence of maternal hyperglycaemia, potentially representing a biological pathway for larger birthweight babies. These results may highlight the need for more intensive dietary and lifestyle interventions among obese women who would not normally receive additional counselling beyond standard antenatal care if not diagnosed with glucose intolerance in pregnancy.

Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells.

Prokineticin 1 (PROK1), a hypoxia-regulated angiogenic factor, has emerged as a crucial regulator of embryo implantation and placentation. Dysregulation of PROK1 has been linked to recurrent pregnancy loss, pre-eclampsia, foetal growth restriction and preterm birth. These pregnancy complications are common in women with obesity and polycystic ovary syndrome, i.e. conditions associated with insulin resistance and compensatory hyperinsulinaemia. We investigated the effect of insulin on PROK1 expression during in vitro decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro. Insulin induced a significant dose-dependent up-regulation of PROK1 on both mRNA and protein level in decidualizing endometrial stromal cells. This up-regulation was mediated by hypoxia-inducible factor 1-alpha (HIF1α) via the phosphatidylinositol 3-kinase (PI3K) pathway. Furthermore, we demonstrated that PROK1 did not affect the viability, but significantly inhibited the migration of endometrial stromal cells and the migratory and invasive capacity of trophoblast cell lines. This in vitro study provides new insights into the regulation of PROK1 by insulin in human decidualizing endometrial stromal cells, the action of PROK1 on migration of endometrial stromal cells, as well as migration and invasion of trophoblasts. We speculate that hyperinsulinaemia may be involved in the mechanisms by which PROK1 is linked to placenta-related pregnancy complications.

Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial.

Metformin therapy is associated with diffuse intestinal (18)F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats.

Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease.

Diabetic cardiomyopathy is characterised in its early stages by diastolic relaxation abnormalities and later by clinical heart failure in the absence of dyslipidaemia, hypertension and coronary artery disease. Insulin resistance, hyperinsulinaemia and hyperglycaemia are each independent risk factors for the development of diabetic cardiomyopathy. The pathophysiological factors in diabetes that drive the development of cardiomyopathy include systemic metabolic disorders, inappropriate activation of the renin-angiotensin-aldosterone system, subcellular component abnormalities, oxidative stress, inflammation and dysfunctional immune modulation. These abnormalities collectively promote cardiac tissue interstitial fibrosis, cardiac stiffness/diastolic dysfunction and, later, systolic dysfunction, precipitating the syndrome of clinical heart failure. Recent evidence has revealed that dysregulation of coronary endothelial cells and exosomes also contributes to the pathology behind diabetic cardiomyopathy. Herein, we review the relationships among insulin resistance/hyperinsulinaemia, hyperglycaemia and the development of cardiac dysfunction. We summarise the current understanding of the pathophysiological mechanisms in diabetic cardiomyopathy and explore potential preventative and therapeutic strategies.

Burden of child and adolescent obesity on health services in England.

To assess the numbers of obese children and young people (CYP) eligible for assessment and management at each stage of the childhood obesity pathway in England.

Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and Protracted Microvascular Retinopathy.

To characterize retinal mitochondrial respiration associated with type 2 diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus Arvicanthis, species niloticus).

Association between fasting insulin and high-sensitivity C reactive protein in Korean adults.

High-sensitivity C reactive protein (hs-CRP) is a reliable indicator of atherosclerotic diseases and is associated with hyperinsulinaemia. The purpose of this study is to examine the association between hs-CRP and fasting insulin levels in Korean adults not taking medication for hypertension, dyslipidaemia or diabetes, nor provided with specific dietary advice.

Acute and long-term administration of palmitoylcarnitine induces muscle-specific insulin resistance in mice.

Acylcarnitine accumulation has been linked to perturbations in energy metabolism pathways. In this study, we demonstrate that long-chain (LC) acylcarnitines are active metabolites involved in the regulation of glucose metabolism in vivo. Single-dose administration of palmitoylcarnitine (PC) in fed mice induced marked insulin insensitivity, decreased glucose uptake in muscles, and elevated blood glucose levels. Increase in the content of LC acylcarnitine induced insulin resistance by impairing Akt phosphorylation at Ser473. The long-term administration of PC using slow-release osmotic minipumps induced marked hyperinsulinemia, insulin resistance, and glucose intolerance, suggesting that the permanent accumulation of LC acylcarnitines can accelerate the progression of insulin resistance. The decrease of acylcarnitine content significantly improved glucose tolerance in a mouse model of diet-induced glucose intolerance. In conclusion, we show that the physiological increase in content of acylcarnitines ensures the transition from a fed to fasted state in order to limit glucose metabolism in the fasted state. In the fed state, the inability of insulin to inhibit LC acylcarnitine production induces disturbances in glucose uptake and metabolism. The reduction of acylcarnitine content could be an effective strategy to improve insulin sensitivity. © 2017 BioFactors, 2017.

Anti-Müllerian hormone in type 2 and gestational diabetes during the second half of pregnancy: relationship with sexual steroid levels and metabolic parameters.

Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during pregnancy. The effect of diabetes on anti-Müllerian hormone (AMH) levels during pregnancy is unclear. The aim of this study was to determine the AMH levels in women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to healthy (C) pregnant women during the second half of gestation. A prospective study of 69 pregnant women with T2D (N: 21), GD (N: 24) and C (N: 24) were followed up during the second half of pregnancy. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. AMH, sexual steroids, insulin, homeostatic model assessment of insulin resistance, HbA1c levels were measured. AMH levels were similar between T2D, GD and C (p = .07). A decline of AMH levels during the second half of gestation was observed in the three groups (p < .0001). AMH levels were negatively associated with age (p < .001). A positive association between AMH and testosterone (p < .05) was found in all groups. A progressive decline of AMH levels is observed in diabetic and healthy women during the second half of pregnancy. Testosterone levels are an independent factor that influences AMH levels during pregnancy. However, AMH levels are not affected by the presence of diabetes during gestation.

Successful treatment of a newborn with congenital hyperinsulinism having a novel heterozygous mutation in the ABCC8 gene using subtotal pancreatectomy.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in newborns and infants. CHI is characterized by unregulated secretion of insulin from pancreatic β: cells. Here, we reported the case of a large-for-gestational-age, full-term newborn that suffered from CHI and developed severe and persistent hypoglycemia at an early stage of life. The infant was nearly unresponsive to medical treatment, which included continuous intravenous glucagon infusion, oral diazoxide, and nifedipine. After medical treatment had failed, an 18-fluoro L-3,4-dihydroxyphenylalanine positron emission tomography scan of the patient showed a focal lesion at the neck of the pancreas. The patient received subtotal pancreatectomy, and shortly after the procedure, the patient's blood sugar returned to the normal range. The patient was confirmed to have a novel heterozygous mutation at position c.2475+1G>A of the ABCC8 gene. This is the first report of a focal form of CHI in a patient in Taiwan, which had preoperatively been confirmed using 18-fluoro L-3,4-dihydroxyphenylalanine positron emission tomography.

Hereditary Tyrosinemia Type 1 in Turkey.

Hereditary tyrosinemia type 1 (HT1, OMIM 276700) is a rare autosomal recessively inherited inborn error of metabolism in the tyrosine catabolic pathway due to deficiency of the enzyme fumarylacetoacetate hydrolase. The clinical features of HT1 are widely heterogenous even within the same family members. Clinical features includes acute or chronic liver disease with increased risk of hepatocellular carcinoma, hypophosphatemic rickets due to renal tubular dysfunction, glomerulosclerosis, failure to thrive, neurological porphyria-like crisis, hypertrophic cardiomyopathy and hypoglycemia due to hyperinsulinism. Currently, the treatment in HT1 consists of two principles: inhibition of the formation of toxic metabolites by nitisinone [2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione; NTBC] and reduction of tyrosine levels by dietary treatment. In this chapter besides presenting the data for 42 patients that had been followed up by Pediatric Metabolic Diseases and Nutrition Unit, Cerrahpasa Medical Faculty, Istanbul University, we also evaluated the data abstracted from the previously published case studies in order to better understand the disease course and gain further insight in the current diagnosis and treatment for HT1 in Turkey.

Glycolate oxidase deficiency in a patient with congenital hyperinsulinism and unexplained hyperoxaluria.

A baby girl was born at 39 weeks gestation to consanguineous Asian parents. From day 1 of life she had severe hypoglycaemia with an inappropriately elevated insulin concentration consistent with congenital hyperinsulinism (CHI), confirmed by the finding of a homozygous mutation in ABCC8 (encoding the sulfonylurea receptor 1).

Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome.

Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS.

Cellular and genetic models of H6PDH and 11β-HSD1 function in skeletal muscle.

Glucocorticoids are important for skeletal muscle energy metabolism, regulating glucose utilization, insulin sensitivity, and muscle mass. Nicotinamide adenine dinucleotide phosphate-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid activation in the sarcoplasmic reticulum (SR) is integral to mediating the detrimental effects of glucocorticoid excess in muscle. 11β-Hydroxysteroid dehydrogenase type 1 activity requires glucose-6-phosphate transporter (G6PT)-mediated G6P transport into the SR for its metabolism by hexose-6-phosphate dehydrogenase (H6PDH) for NADPH generation. Here, we examine the G6PT/H6PDH/11β-HSD1 triad in differentiating myotubes and explore the consequences of muscle-specific knockout of 11β-HSD1 and H6PDH. 11β-Hydroxysteroid dehydrogenase type 1 expression and activity increase with myotube differentiation and in response to glucocorticoids. Hexose-6-phosphate dehydrogenase shows some elevation in expression with differentiation and in response to glucocorticoid, while G6PT appears largely unresponsive to these particular conditions. When examining 11β-HSD1 muscle-knockout mice, we were unable to detect significant decrements in activity, despite using a well-validated muscle-specific Cre transgene and confirming high-level recombination of the floxed HSD11B1 allele. We propose that the level of recombination at the HSD11B1 locus may be insufficient to negate basal 11β-HSD1 activity for a protein with a long half-life. Hexose-6-phosphate dehydrogenase was undetectable in H6PDH muscle-knockout mice, which display the myopathic phenotype seen in global KO mice, validating the importance of SR NADPH generation. We envisage these data and models finding utility when investigating the muscle-specific functions of the 11β-HSD1/G6PT/H6PDH triad.

Serum vaspin level as a predictive indicator in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty.

This study is all about predicting the value of serum vaspin level in the amelioration of fatty liver and metabolic disturbance in patients with severe obesity after laparoscopic vertical banded gastroplasty (LVBG).

QUALITY OF LIFE OF PATIENTS WITH METABOLIC SYNDROME IS IMPROVED AFTER WHOLE BODY VIBRATION EXERCISES.

Whole body vibration exercises (WBVE) improve the quality of life (QoL) of different populations. Metabolic syndrome patients (MetS) may be favored by physical activity. Questionnaires are used to assess the QoL. The aim was to evaluate the QoL of patients with MetS that have undergone WBVE with a brief WHOQOL (WHOQOL-BREF).

Both Low Blood Glucose and Insufficient Treatment Confer Risk of Neurodevelopmental Impairment in Congenital Hyperinsulinism: A Multinational Cohort Study.

Congenital hyperinsulinism (CHI) is a heterogeneous disease most frequently caused by KATP-channel (ABCC8 and KCNJ11) mutations, with neonatal or later onset, variable severity, and with focal or diffuse pancreatic involvement as the two major histological types. CHI confers a high risk of neurological impairment; however, sparsely studied in larger patient series. We assessed the neurodevelopmental outcome in children with CHI at follow-up in a mixed international cohort.

Loss of prion protein is associated with the development of insulin resistance and obesity.

Prion protein (PrP(C)) was initially described due to its involvement in transmissible spongiform encephalopathies. It was subsequently demonstrated to be a cell surface molecule involved in many physiological processes, such as vesicle trafficking. Herein, we investigated the roles of PrP(C) in the response to insulin and obesity development.  Two independent PrP(C) knockout (KO) and one PrP(C) overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored. PrP(C) KO mice fed high-fat diets presented all of the symptoms associated with the development of insulin resistance: hyperglycemia, hyperinsulinemia, and obesity. Conversely, TG20 animals fed high-fat diets showed reduced weight and insulin resistance. Accordingly, the expression of PPARγ was reduced in PrP(C) KO mice and increased in TG20 animals. PrP(C) KO cells also presented reduced glucose uptake upon insulin stimulation, due to reduced translocation of the glucose transporter Glut4.   Thus, our results suggests that PrP(C) reflects susceptibility to the development of insulin resistance and metabolic syndrome.