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Hyperinsulinemia - Top 30 Publications

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.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Functional and Metabolomic Consequences of ATP-dependent Potassium Channel Inactivation in Human Islets.

Loss-of-function mutations of β-cell KATP channels cause the most severe form of congenital hyperinsulinism (KATPHI). KATPHI is characterized by fasting and protein-induced hypoglycemia that is unresponsive to medical therapy. For a better understanding of the pathophysiology of KATPHI, we examined cytosolic calcium, insulin secretion, oxygen consumption, and [U-(13)C]glucose metabolism in islets isolated from the pancreases of children with KATPHI who required pancreatectomy. Basal cytosolic calcium ([Ca(2+)] i ) and insulin secretion were higher in KATPHI islets compared to controls. Unlike controls, insulin secretion in KATPHI islets increased in response to amino acids but not to glucose. KATPHI islets have increased basal rate of oxygen consumption and mitochondrial mass. [U-(13)C]glucose metabolism showed a 2-fold increase in alanine levels and 6-fold increase in (13)C enrichment of alanine in KATPHI islets, suggesting increased rates of glycolysis. KATPHI islets also exhibited increased serine/glycine and glutamine biosynthesis. In contrast, KATPHI islets had low GABA levels and lacked of (13)C incorporation into GABA in response to glucose stimulation. The expression of key genes involved in these metabolic pathways was significantly different in KATPHI β-cells compared to control, providing a mechanism for the observed changes. These findings demonstrate that the pathophysiology of KATPHI is complex and they provide a framework for the identification of new potential therapeutic targets for this devastating condition.

Congenital Hyperinsulinism Caused by a De Novo Mutation in the ABCC8 Gene - A Case Report.

Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by inappropriate insulin secretion and severe hypoglycaemia. There are two histological subtypes: diffuse and focal form. Diffuse form is most common in autosomal recessive mutations in ABCC8/KCNJ11 gene, while focal CHI is caused a paternally inherited mutation and a somatic maternal allele loss. Here we report a case of a term male infant presented with severe hyperinsulinaemic hypoglycaemia. Gene panel testing was performed to give rapid genetic diagnosis. We detected the c.4415-13G>A heterozygous mutation in the ABCC8 gene. Targeted genetic testing of the parents proved the de novo origin of the mutation. The mutation has been previously described. The infant received octreotide treatment and is prepared for 18-fluoro-dopa PET-CT examination in order to localize the lesion. Rapid genetic testing might be crucial in the clinical management strategy, with decision algorithms taking into account of the genetic status of the patient.

Gene expression profile of subcutaneous adipose tissue in BMI-discordant monozygotic twin pairs unravels molecular and clinical changes associated with sub-types of obesity.

Subcutaneous adipose tissue (SAT) undergoes major changes in obesity, but little is known about the whole-genome scale patterns of these changes or about their variation between different obesity subgroups. We sought to compare how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who are discordant for body mass index (BMI), whether the profiles vary between twin pairs and whether the variation can be linked to clinical characteristics.

Polycystic kidney disease: PMM2 mutation causes PKD and hyperinsulinism.

Impaired endothelium-derived hyperpolarization-type relaxation in superior mesenteric arteries isolated from female Otsuka Long-Evans Tokushima Fatty rats.

Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks. We investigated concentration-relaxation curves for acetylcholine (at age 50-53 weeks), NS309 (an activator of small- and intermediate-conductance calcium-activated potassium channels) (at age 50-53 weeks), and GSK1016790A (an agonist of transient receptor potential vanilloid type 4, TRPV4) (at age 58 or 59 weeks) in the presence of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine and the cyclooxygenase inhibitor indomethacin to investigate EDH-type responses in the superior mesenteric artery. Obesity, mild hyperglycemia, hyperinsulinemia, and hyperlipidemia (i.e., increased total cholesterol, triglyceride, and non-esterified fatty acids) were more frequent in OLETF rats than in age-matched LETO rats at age 50-53 weeks. Acetylcholine-, NS309-, and GSK1016790A-induced relaxations in arteries from OLETF rats were all significantly reduced compared to those in LETO rats. These results indicated that EDH-type relaxations were impaired in female OLETF rats. This novel experimental model may provide new insights into vascular dysfunction in metabolic syndrome in females.

Prohibitin-induced obesity leads to anovulation and polycystic ovary in mice.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the most common cause of female infertility. However, the etiology of the disease and the mechanisms by which this disorder progress remain unclear. Here we report that a transgenic obese mouse (Mito-Ob) developed by overexpressing prohibitin in adipocytes develops polycystic ovaries. Initially, the female Mito-Ob mice were equally fertile to their wild-type littermates. Mito-Ob mice begin to gain weight after puberty, become significantly obese between 3-6 months of age, and roughly 25% of them become infertile by 9 months of age. Despite obesity, female Mito-Ob mice maintained glucose homeostasis and insulin sensitivity similar to their wild-type littermates. Mito-Ob mice showed morphologically distinct polycystic ovaries and elevated estradiol, but normal testosterone and insulin levels. Histological analysis of the ovaries showed signs of impaired follicular dynamics like preantral follicular arrest and reduced number, or absence of corpus luteum. The ovaries in infertile Mito-Ob mice were found closely surrounded by periovarian adipose tissue suggesting a potential role in anovulation. Collectively, these data suggest that elevated estradiol and obesity per se may lead to anovulation and polycystic ovaries independent of hyperinsulinemia and hyperandrogenism. As obesity often coexists with other abnormalities known to be involved in the development of PCOS such as insulin resistance, compensatory hyperinsulinemia, and hyperandrogenism, the precise role of these factors in the disease process remain unclear. The Mito-Ob mice provide an opportunity to study the effect of obesity on anovulation and ovarian cyst formation independent of the major drivers of obesity-linked PCOS.

Interleukin-6 increases the expression and activity of insulin-degrading enzyme.

Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.

Neck Circumference Is Associated with Muscle Sympathetic Nerve Activity in Overweight and Obese Men but Not Women.

Background: Neck circumference (NC) is a predictor of cardiometabolic risk. The objective of this study was to explore the relationship of NC to muscle sympathetic nerve activity (MSNA) within an overweight and obese population. Methods: The study design was a retrospective cross-sectional analysis. Un-medicated persons (72 men, 53 postmenopausal women) aged 56 ± 1 years (mean ± SEM) with body mass index (BMI) 32.8 ± 0.4 kg/m(2), were studied. NC was measured together with traditional anthropometric measures, supine blood pressure, fasting blood lipids, insulin, and glucose. Insulin sensitivity was assessed by homeostasis model (HOMA-IR) and Matsuda Insulin Sensitivity Index (ISI) derived from 75-g oral glucose tolerance test. Resting multiunit MSNA was recorded by microneurography in the peroneal nerve and expressed as burst frequency and burst incidence. Results: Men within the highest tertile of NC had significantly higher fasting and post-glucose plasma insulin levels (insulin AUC0-120), HOMA-IR, non-esterified fatty acids, MSNA (45 ± 2 vs. 36 ± 2 bursts per min; 69 ± 3 vs. 58 ± 3 bursts per 100 hb) and heart rate, and lower Matsuda ISI compared to men in the lowest tertile (P all <0.05). In stepwise regression analyses, NC alone explained 12%, and together with insulin AUC0-120 it accounted for 22%, of the variance in MSNA in men. In women, NC was associated with anthropometric measures but not with MSNA or metabolic indices. Conclusions: Among overweight and obese men, NC was independently associated with elevated MSNA and hyperinsulinemia, and thus may be relevant to cardiometabolic risk prediction. The biological basis of gender differences merits further elucidation.

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones.

Fatty liver can be diet, endocrine, genetic, viral, or drug induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic, and ketogenic genes, promoting hyperglycemia, hyperlipidemia, and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency, and elevated sympathetic tone. These endocrine and metabolic changes further encourage hepatic steatosis by regulating adipose tissue lipolysis, liver lipid uptake, de novo lipogenesis (DNL), beta-oxidation, ketogenesis, and lipid export. Hepatic lipid accumulation may be induced through 4 separate mechanisms: 1) increased hepatic uptake of circulating fatty acids, 2) increased hepatic de novo fatty acid synthesis, 3) decreased hepatic beta-oxidation, and 4) decreased hepatic lipid export. This review will discuss the hormonal regulation of each mechanism comparing multiple physiological models of hepatic lipid accumulation. Nonalcoholic fatty liver disease (NAFLD) is typified by increased hepatic lipid uptake, synthesis, oxidation, and export. Chronic hepatic lipid signaling through PPARgamma results in gene expression changes that allow concurrent activity of DNL and beta-oxidation. The importance of hepatic steatosis in driving systemic metabolic dysfunction is highlighted by the common endocrine and metabolic disturbances across many conditions that result in fatty liver. Understanding the mechanisms underlying the metabolic dysfunction that develops as a consequence of hepatic lipid accumulation is critical to identifying points of intervention in this increasingly prevalent disease state.

Effect of amyloid-Β (25-35) in hyperglycemic and hyperinsulinemic rats, effects on phosphorylation and O-GlcNAcylation of tau protein.

Aggregation of the amyloid beta (Aβ) peptide and hyperphosphorylation of tau protein, which are markers of Alzheimer's disease (AD), have been reported also in diabetes mellitus (DM). One regulator of tau phosphorylation is O-GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation and phosphorylation of tau protein were evaluated in the brain of rats with streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with the Aß25-35 peptide in the hippocampal region CA1. Weight, glycated hemoglobin, glucose, and insulin were determined. Male Wistar rats were divided in groups (N=20): a) control, b) treated only with the Aβ25-35 peptide, c) treated with Aβ25-35 and STZ, and d) treated only with STZ. Results showed statistically significant differences in the mean weight, glucose levels, insulin concentration, and HbA1c percentage, between C- and D-treated groups and not STZ-treated A and B (P<0.05). Interestingly, our results showed diminution of O-GlcNAcylation and increase in P-tau-Ser-396 in the hippocampal area of the Aβ25-35- and STZ-treated groups; moreover, enhanced expression of GSK3beta was observed in this last group. Our results suggest that hyperinsulinemia-Aβ25-35-hyperglycemia is relevant for the down regulation of O-GlcNAcylation and up-regulation of the glycogen synthase kinase-3 beta (GSK3beta), favoring Aβ25-35-induced neurotoxicity in the brain of rats.

Hypoglycemia identified by a continuous glucose monitoring system in a second-trimester pregnant woman with insulinoma: a case report.

Insulinoma associated with pregnancy is a very rare condition and can be difficult to diagnose. Here, we present an interesting case of insulinoma occurring during pregnancy with special attention paid to the use of a continuous glucose monitoring system to detect hypoglycemia.

miR-29a regulated ER-positive breast cancer cell growth and invasion and is involved in the insulin signaling pathway.

Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration. We found that miR-29a-induced cell proliferation and metastasis acceleration occurred primarily through ERK phosphorylation. The IGF-1R is the upstream target gene of miR-29a, while CDC42 and p85α are the downstream target genes of miR-29a. These results have provided us with information regarding the molecular mechanisms by which hyperinsulinemia promotes breast cancer occurrence and development and thus leads to a poor prognosis in breast cancer patients and indicate that miR-29a plays an important role in breast cancer development and invasion.

Vitamin D status and its association with insulin resistance among type 2 diabetics: A case -control study in Ghana.

Vitamin D plays a major role in physiological processes that modulate mineral metabolism and immune function with probable link to several chronic and infectious conditions. Emerging data suggests a possible influence of vitamin D on glucose homeostasis. This study sought to provide preliminary information on vitamin D status among Ghanaian type 2 diabetics and assessed its association with glucose homeostasis.

Modeling the shape and composition of the human body using dual energy X-ray absorptiometry images.

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes.

Metabolic syndrome, serum uric acid and renal risk in patients with T2D.

Metabolic Syndrome (Mets) and increased serum uric acid (SUA), are well known renal risk predictors and often coexist in patients with type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD is at present unclear.

Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in the Brain.

The brain is vulnerable to hypoglycaemia due to a continuous need of energy substrates to meet its high metabolic demands. Studies have shown that severe acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain, when neuroglycopenia cannot be evaded despite increased levels of cerebral glucose transporters. Compensatory measures in the brain during chronic insulin-induced hypoglycaemia are less well understood. The present study investigated how the brain of nondiabetic rats copes with chronic insulin-induced hypoglycaemia for up to eight weeks. Brain level of different substrate transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in controls). The animals had increased food consumption, body weights, and hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose transporter were decreased, whereas levels of lipid peroxidation products were unchanged. Discontinued infusion was followed by transient systemic hyperglycaemia and decreased food consumption and body weight. After 4 weeks, plasma levels of lipid peroxidation products were increased, possibly as a consequence of hyperglycaemia-induced oxidative stress. The present data suggests that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose transporter levels, which may be leptin-induced.

High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process.

Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2 diabetes mellitus), are associated with menstrual dysfunction, anovulation, infertility, and early pregnancy loss. Ovarian dysfunction is not only related to low pregnancy rates but also to the increased risk of miscarriage. Women with PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian dysfunction. In this study, we first explored whether high insulin levels directly affected ovarian functioning during embryo implantation. Mice in the insulin-treated group were given a subcutaneous injection of human recombinant insulin. After insulin treatment, serum levels of E2 (estrogen), PROG (progesterone), LH (luteinizing hormone), and FSH (follicle-stimulating hormone) were obviously lower, and there was a significant decrement of ovarian GDF9 (growth differentiation factor 9) mRNA. H&E (hematoxylin and eosin) staining showed a greater number of immature follicles and less luteinization in the insulin group. Further autophagy was studied in this process. A significant increase of P62 (SQSTM1/Sequestosome1) and a decrease of Cathepsin B, BECN1 (Beclin 1), and ULK1 (Unc-51-like kinase 1) mRNA in ovary was found in the insulin group. Western blot analysis showed that the expressions of LC3 (microtubule-associated protein 1 light chain 3), BECN1, and Cathepsin B proteins in ovaries from insulin group were obviously reduced, while P62 proteins were significantly increased. All these results illustrated that insulin could directly impair ovarian function during embryo implantation and the imbalance of ovarian autophagy due to insulin. Autophagy could enhance the impaired ovarian function results from insulin.

Evaluation of Chinese Herbal Medicine Jinlida in Type 2 Diabetes Patients based on Stratification: Results of Subgroup Analysis from 12-Week Trial.

Previous study found that the Chinese Herbal Medicine Jinlida could significantly enhance the hypoglycemic action of metformin compared to metformin alone. However, the advantage of Jinlida has not been clarified yet. We aimed to compare the efficacy of Jinlida in patients with T2DM based on stratification.

High Glucose Accelerates Cell Proliferation and Increases the Secretion and mRNA Expression of Osteopontin in Human Pancreatic Duct Epithelial Cells.

The incidence of pancreatic cancer is increasing year-by-year in Japan. Among the diseases that complicate pancreatic cancer, diabetes is the most common. Recently, it has become evident that patients suffering from diabetes and obesity show increased expression of osteopontin (OPN). The purpose of this study was to investigate the effect of high glucose and high insulin culture conditions on a human pancreatic duct epithelial cell line (HPDE-6), focusing particularly on OPN expression.

Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.

One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability.

Unraveling the Regulation of Hepatic Metabolism by Insulin.

During insulin-resistant states such as type 2 diabetes mellitus (T2DM), insulin fails to suppress hepatic glucose production but promotes lipid synthesis leading to hyperglycemia and hypertriglyceridemia. Defining the downstream signaling pathways underlying the control of hepatic metabolism by insulin is necessary for understanding both normal physiology and the pathogenesis of metabolic disease. We summarize recent literature highlighting the importance of both hepatic and extrahepatic mechanisms in insulin regulation of liver glucose and lipid metabolism. We posit that a failure of insulin to inappropriately regulate liver metabolism during T2DM is not exclusively from an inherent defect in canonical liver insulin signaling but is instead due to a combination of hyperinsulinemia, altered substrate supply, and the input of several extrahepatic signals.

Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy patient.

We have recently published on the limited effectiveness of sirolimus as a treatment option for hypoglycaemia as a consequence of hyperinsulinism. Our data oppose the view that mTOR inhibitors provide new opportunities for the treatment of patients with hyperinsulinism. We are not convinced by the argument that any benefit for some patients outweighs the potential and later long-term problems that accompany mTOR inhibition in the neonate. We also express the opinion that caution must be taken when repurposing/repositioning therapies in the field of rare disease.

Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts.

Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race.

Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort.

The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study.

Effect of Intravenous Small-Volume Hypertonic Sodium Bicarbonate, Sodium Chloride, and Glucose Solutions in Decreasing Plasma Potassium Concentration in Hyperkalemic Neonatal Calves with Diarrhea.

Hyperkalemia is a frequently observed electrolyte imbalance in dehydrated neonatal diarrheic calves that can result in skeletal muscle weakness and life-threatening cardiac conduction abnormalities and arrhythmias.

Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome.

To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR).

Multiphasic Regulation of Systemic and Peripheral Organ Metabolic Responses to Cardiac Hypertrophy.

Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy.

Xanthine oxidoreductase activity is correlated with insulin resistance and subclinical inflammation in young humans.

The enzyme xanthine oxidoreductase (XOR) catalyzes the formation of uric acid (UA) from hypoxanthine and xanthine, which in turn are products of purine metabolism starting from ribose-5-phosphate. Besides the synthesis of UA, basic research has suggested that XOR is involved in the regulation of reactive oxygen species, adipogenesis, and peroxisome proliferator-activated receptor-γ (PPAR-γ). XOR activity has shown to be much lower in humans than in rodents, which makes its accurate measurement difficult. Recently, a novel human plasma XOR activity assay has been established using a combination of liquid chromatography (LC) and triple quadrupole mass spectrometry (TQMS) to detect [(13)C2,(15)N2]UA using [(13)C2,(15)N2]xanthine as a substrate. Using this novel assay, we for the first time determine plasma XOR activity in humans, and evaluate its association with insulin resistance, high-sensitivity C-reactive protein (hsCRP) levels, and other parameters.