Lower Insulin Levels Research Articles

Effects of soy consumption on metabolic parameters in patients with metabolic syndrome: A systematic review and meta-analysis.

Functional foods like soy have unique effects on health status. Although various dietary modifications have been recommended to ameliorate features of metabolic syndrome (MetS), no meta-analysis has summarized the effect of soy consumption in patients with MetS. PubMed, ISI Web of Science, and Scopus were searched for relevant articles until Jun 2020, resulting in six relevant publications that were included in our meta-analysis. Combining a total of 9 comparisons suggested a significant decrease in serum levels of triglyceride (WMD: -0.29; 95 % CI: -0.49, -0.09 mg/dL), total cholesterol (WMD: -1.46; 95 % CI: -1.70, -1.22 mg/dL), LDL-C (WMD: -0.73; 95 % CI: -0.93, -0.52 mg/dL) and no change in serum HDL-c levels. Combining a total of 7 effect sizes examining soy effects on glycemic parameters indicated that subjects who consumed soy products had lower levels of fasting blood sugar (WMD: -0.90; 95 % CI: -1.12, -0.68 mg/dL), insulin (WMD: -1.06; 95 % CI: -1.29, -0.84 pmol/ L) and HOMA-IR (WMD: -1.08; 95 % CI: -1.31, -0.85) compared with those in the control group. Soy consumption could not significantly change anthropometric measures and blood pressure. Consuming soy products in patients with MetS effectively improved lipid profile and glycemic parameters independent of affecting anthropometric measures.

The role of C-peptide in regulation of the insulin signaling system (systematic review)

The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new evidence has emerged indicating that C-peptide is involved not only in the processing of insulin in the secretory granules of pancreatic β-cells, but also has an important regulatory effect on the functions of many organs and tissues. C-peptide mediates physiological effects through signaling pathways by binding to a specific receptor on the cell membrane. Intracellular signaling occurs through the G-protein and Ca 2+ - dependent pathways, which leads to the activation and increased expression of endothelial nitric oxide synthase, Na + /K + -ATPase, and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. One of the most important physiological effects of C-peptide is the regulation and modification of insulin signaling mechanisms. The nature of the effect of C-peptide on the insulin signaling system depends on the concentration of insulin. It is assumed that under conditions of low insulin levels, the C-peptide receptor binds to G i/o -proteins and leads to increased activation of processes induced by insulin. In this case, the C-peptide acts as insulin-mimetic peptide. Under high insulin conditions, the C-peptide receptor binds to G q/11 -proteins and leads to activation of protein kinase C with subsequent weakening of insulin-related signaling cascades. This review presents new facts indicating the participation of C-peptide in the regulation of the insulin signaling system.

Alterations in Insulin Levels in Adults with Prenatal Alcohol Exposure

Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences. A prospective cohort of predominantly African-American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA-IR) was also computed. Body mass index (BMI) was calculated and normal defined as<25kg/m2 . Participants were categorized as having PAE (n=39) if their mothers drank at least 1 ounce of absolute alcohol per week or more during the 1st trimester of pregnancy and as Controls (n=22) if their mothers reported abstaining from alcohol consumption during pregnancy. Mean age of the sample was 36.0±1.5years. Indices of glucose metabolism, including fasting plasma glucose and hemoglobin A1c levels, did not vary by group status but insulin levels and HOMA-IR values varied by group status and BMI level. PAE individuals with a normal BMI had lower insulin levels than Controls. However, in PAE subjects, there was a steeper increase in insulin levels relative to their BMI than in Control subjects. A cluster of 5 PAE cases had low levels of insulin and 4 of the 5 had severe cognitive impairment. The bidirectional effects on insulin level and insulin resistance associated with PAE may indicate differential rates of diabetes disease impact or differential PAE impact in the brain and peripheral areas involved in insulin production and signaling. These alterations may contribute to the metabolic disease risk associated with PAE.

The mTORC1 complex in pre-osteoblasts regulates whole-body energy metabolism independently of osteocalcin

Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin resistance. In osteoblasts (OBs), insulin signaling plays a crucial role in the control of systemic glucose homeostasis. We utilized mice with conditional deletion of Rptor to investigate how the loss of mTORC1 function in OB affects glucose metabolism under normal and overnutrition dietary states. Compared to the controls, chow-fed Rptorob−/− mice had substantially less fat mass and exhibited adipocyte hyperplasia. Remarkably, upon feeding with high-fat diet, mice with pre- and post-natal deletion of Rptor in OBs were protected from diet-induced obesity and exhibited improved glucose metabolism with lower fasting glucose and insulin levels, increased glucose tolerance and insulin sensitivity. This leanness and resistance to weight gain was not attributable to changes in food intake, physical activity or lipid absorption but instead was due to increased energy expenditure and greater whole-body substrate flexibility. RNA-seq revealed an increase in glycolysis and skeletal insulin signaling pathways, which correlated with the potentiation of insulin signaling and increased insulin-dependent glucose uptake in Rptor-knockout osteoblasts. Collectively, these findings point to a critical role for the mTORC1 complex in the skeletal regulation of whole-body glucose metabolism and the skeletal development of insulin resistance.

Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study

IntroductionCurrent dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide...

Comparing the Anti-diabetic Effect of Sleeve Gastrectomy with Transit Bipartition Against Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Using a Diabetic Rodent Model.

Roux-en-Y gastric bypass (RYGB) has superior long-term diabetes remission outcomes to sleeve gastrectomy (SG). However, in regions with a high prevalence of gastric cancer, RYGB may not be the best option. This study aimed to investigate the anti-diabetic effect of SG with transit bipartition (SG-TB) compared with SG and RYGB. A total of 32 diabetic Sprague-Dawley rat models were assigned to one of four groups: SG (n = 8), RYGB (n = 8), SG-TB (n = 8), and SHAM (n = 8). Body weight, food intake, blood glucose, and hormonal changes (glucagon-like peptide-1 (GLP-1), insulin, and glucagon) were measured to investigate the effect of surgery in all groups. Oral glucose tolerance test and insulin tolerance test were performed before and 8 weeks after surgery. There were no significant differences in the postoperative changes in body weight and food intake among the SG, RYGB, and SG-TB groups. Postoperatively, the RYGB and SG-TB groups had significantly higher GLP-1 levels and lower insulin levels than the SG group. Further, RYGB and SG-TB had significantly better glucose control improvements than SG. There were no significant differences in GLP-1, insulin, glucagon, and homeostasis model assessment of insulin resistance levels between RYGB and SG-TB. The preoperative and postoperative values of all variables in the SHAM group did not show significant differences. In this study using a diabetes-induced rodent model, we found that the anti-diabetic effect of SG-TB is superior to that of SG and non-inferior to that of RYGB.

Sonic Hedgehog receptor Patched deficiency in astrocytes enhances glucose metabolism in mice

ObjectiveAstrocytes are glial cells proposed as the main Sonic hedgehog (Shh)-responsive cells in the adult brain. Their roles in mediating Shh functions are still poorly understood. In the hypothalamus, astrocytes support neuronal circuits implicated in the regulation of energy metabolism. In this study, we investigated the impact of genetic activation of Shh signaling on hypothalamic astrocytes and characterized its effects on energy metabolism. MethodsWe analyzed the distribution of gene transcripts of the Shh pathway (Ptc, Gli1, Gli2, and Gli3) in astrocytes using single molecule fluorescence in situ hybridization combined with immunohistofluorescence of Shh peptides by Western blotting in the adult mouse hypothalamus. Based on the metabolic phenotype, we characterized Glast-CreERT2-YFP-Ptc−/− (YFP-Ptc−/−) mice and their controls over time and under a high-fat diet (HFD) to investigate the potential effects of conditional astrocytic deletion of the Shh receptor Patched (Ptc) on metabolic efficiency, insulin sensitivity, and systemic glucose metabolism. Molecular and biochemical assays were used to analyze the alteration of key pathways modulating energy metabolism, insulin sensitivity, glucose uptake, and inflammation. Primary astrocyte cultures were used to evaluate a potential role of Shh signaling in astrocytic glucose uptake. ResultsShh peptides were the highest in the hypothalamic extracts of adult mice and a large population of hypothalamic astrocytes expressed Ptc and Gli1-3 mRNAs. Characterization of Shh signaling after conditional Ptc deletion in the YFP-Ptc−/− mice revealed heterogeneity in hypothalamic astrocyte populations. Interestingly, activation of Shh signaling in Glast+ astrocytes enhanced insulin responsiveness as evidenced by glucose and insulin tolerance tests. This effect was maintained over time and associated with lower blood insulin levels and also observed under a HFD. The YFP-Ptc−/− mice exhibited a lean phenotype with the absence of body weight gain and a marked reduction of white and brown adipose tissues accompanied by increased whole-body fatty acid oxidation. In contrast, food intake, locomotor activity, and body temperature were not altered. At the cellular level, Ptc deletion did not affect glucose uptake in primary astrocyte cultures. In the hypothalamus, activation of the astrocytic Shh pathway was associated with the upregulation of transcripts coding for the insulin receptor and liver kinase B1 (LKB1) after 4 weeks and the glucose transporter GLUT-4 after 32 weeks. ConclusionsHere, we define hypothalamic Shh action on astrocytes as a novel master regulator of energy metabolism. In the hypothalamus, astrocytic Shh signaling could be critically involved in preventing both aging- and obesity-related metabolic disorders.

Maternal swimming mitigates liver damage caused by paternal obesity

ObjectivesParents' lifestyle and nutrition can program offspring obesity in adulthood. We hypothesized that maternal swimming has beneficial effects on the adversity caused by paternal obesity on offspring. MethodsTwelve-week-old male C57 BL/6 J mice (fed a high-fat diet, obese father [ObFa], or control diet, lean father [LFa]) were mated with female mice fed only the control diet. Mothers were trained (TMo) or untrained (UMo): swimming for 6 wk before and the first 2 wk of gestation. Pups were fed only the control diet. ResultsFathers showed different body mass (BM) at copulation, but not the mothers. The ObFa had 20% higher BM than the LFa. Twelve-week-old ObFa/UMo offspring showed a higher BM gain than the LFa/UMo and ObFa/TMo. There was BM sexual dimorphism in the LFa/UMo (female mice +24% than male mice). There was hyperglycemia and hyperinsulinemia in the ObFa/UMo, but low glycemia and insulin levels were seen in the ObFa/TMo. There was augmented liver steatosis in the ObFa/UMo compared with the LFa/UMo, and the ObFa/TMo compared with the LFa/TMo, but reduced steatosis in the ObFa/TMo compared with the ObFa/UMo. In addition, lipogenic markers were more expressed and beta-oxidation markers less expressed in the ObFa/UMo compared with the LFa/UMo, but the opposite was observed in the ObFa/TMo compared with the ObFa/UMo. Proinflammatory markers were higher in the liver of the ObFa/UMo compared with the LFa/UMo and lower in the ObFa/TMo compared with the ObFa/UMo. ConclusionsObese fathers produced offspring that were overweight and had altered fasting glycemia and insulin sensitivity, leading to higher liver lipogenesis and inflammation, as well as lower beta-oxidation. The swimming mother mitigated these adverse effects in mice offspring.

Acupoint Catgut Embedding Reduces Insulin Resistance in Diabetic Patients Undergoing Open Cardiac Surgery.

Acupoint catgut embedding (ACE) has been used safely for thousands of years in traditional Chinese medicine. The aim of this study was to assess whether ACE can improve insulin resistance and promote rapid recovery after open cardiac surgery. A group of 200 patients undergoing cardiac surgery were randomly allocated to receive either ACE (ACE group) or sham ACE (SHAM group). The primary outcome of our trial was insulin resistance assessed 1, 3, 5, and 7 days after surgery. The homeostasis model assessment (HOMA-IR) was used to measure perioperative insulin resistance. Secondary outcomes included insulin, glucose, and inflammatory cytokine (interleukin (IL) 6 and IL-8) levels; time to extubation; incidence of infection; time to first feces; acute kidney injury; incidence of postoperative nausea and vomiting (PONV); length of stay in the ICU; length of hospital stay; and other clinical parameters. The ACE group had lower insulin, glucose, IL-6, IL-8, and HOMA-IR levels than the SHAM group one week after the operation. The incidence of infection, incidence of PONV, time to drain removal, and length of hospital stay significantly were lower in the ACE group than in the SHAM group. ACE can improve insulin resistance and promote rapid recovery after open cardiac surgery.

A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors.

Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors. Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin-releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin-like growth factor (IGF-1), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin/neurokinin B/dynorphin) act on GnRH neurons and a multitude of factors result in their release. Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well-being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under-recognized and under-treated clinical entity will aid management and may result in the development of novel therapeutic approaches.

INSULIN RESISTANCE IN PATIENTS WITH PANCREATIC AND COLORECTAL CANCER DIAGNOSED AGAINST THE BACKGROUND OF TYPE 2 DIABETES MELLITUS

The aim of the study was to investigate insulin resistance in patients with pancreatic and colorectal cancer diagnosed in people with type 2 diabetes.&#x0D; Materials and methods. 64 patients were examined. They were divided into the following groups: group I – healthy people (control group) (n = 16); group II – patients with type 2 diabetes without cancer (n = 28); group IIIa – patients with type 2 diabetes with pancreatic cancer (n = 10), group IIIb – patients with type 2 diabetes with colorectal cancer (n = 10). The study involved patients from specialized departments of the Ivano-Frankivsk Regional Hospital and the Precarpathian Clinical Oncology Center.&#x0D; Blood insulin levels were determined by enzyme-linked immunosorbent assay, using Insulin ELISA diagnostic kits, EIA-2935. Fasting blood glucose was determined by glucose oxidase method. Compensation for diabetes was assessed by the level of glycated hemoglobin (HbA1c) and determined by ion exchange chromatography. Data analysis was performed using Statistica 12.0 (StatSoft Inc., USA). Differences between the values in the comparison groups were determined by Student’s t-test and were considered significant at P &lt; 0.05.&#x0D; Results. Patients with type 2 diabetes who were diagnosed with pancreatic cancer or colorectal cancer were older, compared with patients with type 2 diabetes without cancer (P &lt; 0.05). Obesity was diagnosed in patients with colorectal cancer of group IIIb, their BMI was higher in comparison with patients of group IIIa who suffered from pancreatic cancer (P &lt; 0.05). BMI in patients of group IIIa was lower than in control group (P &lt; 0.05), in patients of group II (P &lt; 0.05) and in patients of group IIIb with colorectal cancer (P &lt; 0.05).&#x0D; Compared with patients of group II, patients with pancreatic and colorectal cancer had significantly lower insulin levels (P &lt; 0.05), but significantly higher fasting blood glucose levels (P &lt; 0.05). Insulin resistance according to the HOMA-IR index (&gt; 3.0) was detected in both types of cancer. The HOMA-IR index in patients with pancreatic cancer was significantly lower than in patients of group II (P &lt; 0.05). The level of HbA1c in patients with type 2 diabetes without cancer and in patients with cancer diagnosed on the background of diabetes did not differ significantly (P &gt; 0.05).&#x0D; Prior to cancer detection, the same number of patients (50.0%) received metformin-free therapy in both the pancreatic cancer group and the colorectal cancer group. However, the duration of diabetes in patients with pancreatic cancer was 2.90 ± 2.60 years and was significantly shorter than in patients with colorectal cancer 9.70 ± 5.66 (P &lt; 0.05). 80.0% of patients in group IIIa had a history of diabetes less than 5 years, and 80.0% of patients in group IIIb – more than 5 years.&#x0D; Conclusions:&#x0D; &#x0D; In patients with type 2 diabetes mellitus with pancreatic cancer, as well as in patients with colorectal cancer, insulin resistance was detected by the HOMA-IR index, which depended on the combined effect of insulin and hyperglycemia in patients with colorectal cancer and on the fasting blood glucose in patients with pancreatic cancer.&#x0D; The absence of hyperinsulinemia, the short duration of type 2 diabetes in patients with pancreatic cancer may be indirect evidence of cancer induced pancreatogenic diabetes (T3cDM) in the majority of patients of this group.&#x0D; For elderly patients with newly diagnosed diabetes mellitus without obesity, without hyperinsulinemia, screening for pancreatic cancer is recommended.&#x0D;

Sleep-wake cycle regularity and cardiometabolic indicators

To evaluate the association between sleep-wake rhythm and cardiometabolic parameters. 103 participants, aged 25-64 years, underwent actigraphy study with Actigraph Actilife GT3X + device (USA) for 7 days. We assessed actigraphy indicators (physical activity and sleep data), anthropometric indicators, blood pressure and laboratory parameters. Actigraphy data was processed using the nparACT package in the R program with the calculation of nonparametric indicators: intraday variability, interday stability, the average level of lowest activity for five hours (L5) and ten hours with the highest activity (M10), relative amplitude is the ratio of M10/L5. The nonparametric analysis showed an association of the higher night activity with sleep effectiveness, wake after sleep onset, indicators of physical activity. A more stable sleep pattern is associated with more steps, less weight and waist circumference, lower levels of diastolic blood pressure, creatinine and insulin. Increased fragmentation of sleep patterns is associated with increased CRP and increased sedentary time. Participants with higher activity contrast have less waist circumference, hips and body mass index, lower levels of CRP and insulin. Rhythm and quality of sleep are important parameters associated with cardiometabolic indicators. Stable sleep patterns, higher activity during the day and lower night activity are associated with a more favorable condition of cardiovascular system.

Disrupted glucose homeostasis and skeletal-muscle-specific glucose uptake in an exocyst knockout mouse model

Skeletal muscle is responsible for the majority of glucose disposal following meals, and this is achieved by insulin-mediated trafficking of glucose transporter type 4 (GLUT4) to the cell membrane. The eight-protein exocyst trafficking complex facilitates targeted docking of membrane-bound vesicles, a process underlying the regulated delivery of fuel transporters. We previously demonstrated the role of exocyst subunit EXOC5 in insulin-stimulated GLUT4 exocytosis and glucose uptake in cultured rat skeletal myoblasts. However, the in vivo role of EXOC5 in skeletal muscle remains unclear. Using mice with inducible, skeletal-muscle-specific knockout of exocyst subunit EXOC5 (Exoc5-SMKO), we examined how muscle-specific disruption of the exocyst would affect glucose homeostasis in vivo. We found that both male and female Exoc5-SMKO mice displayed elevated fasting glucose levels. Additionally, male Exoc5-SMKO mice had impaired glucose tolerance and lower serum insulin levels. Using indirect calorimetry, we observed that male Exoc5-SMKO mice have a reduced respiratory exchange ratio during the light period and lower energy expenditure. Using the hyperinsulinemic–euglycemic clamp method, we further showed that insulin-stimulated skeletal muscle glucose uptake is reduced in Exoc5-SMKO males compared with wild-type controls. Overall, our findings indicate that EXOC5 and the exocyst are necessary for insulin-stimulated glucose uptake in skeletal muscle and regulate glucose homeostasis in vivo.

Inhibition of the Keap1/Nrf2 Signaling Pathway Significantly Promotes the Progression of Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency due to pancreatic β-cell damage and leads to hyperglycemia. The precise molecular mechanisms of the etiology of T1DM are not completely understood. Oxidative stress and the antioxidant status of pancreatic β-cells play a vital role in the pathogenesis and progression of T1DM. The Keap1/Nrf2 signaling pathway plays a critical role in cellular resistance to oxidative stress. This study is aimed at investigating the role of the Keap1/Nrf2 signaling pathway in the progression of T1DM. An alloxan- (ALX-) stimulated T1DM animal model in wild-type (WT) and Nrf2 knockout (Nrf2−/−) C57BL/6J mice and a mouse pancreatic β-cell line (MIN6) were established. Compared with the tolerant (ALX exposure, nondiabetic) WT mice, the sensitive (ALX exposure, diabetic) WT mice exhibited higher blood glucose levels and lower plasma insulin levels. The Keap1/Nrf2 signaling pathway was significantly inhibited in the sensitive WT mice, which was reflected by overexpression of Keap1 and low expression of Nrf2, accompanied by a marked decrease in the expression of the antioxidative enzymes. Compared with WT mice, the Nrf2−/− mice had an increased incidence of T1DM and exhibited more severe pancreatic β-cell damage. The results of in vitro experiments showed that ALX significantly inhibited the viability and proliferation and promoted the apoptosis of MIN6 cells. ALX also markedly increased intracellular ROS production and caused DNA damage in MIN6 cells. In addition, the Keap1/Nrf2 signaling pathway was significantly inhibited in the damaged MIN6 cells. Moreover, Nrf2 silencing by transfection with Nrf2 siRNA markedly exacerbated ALX-induced MIN6 cell injury. Conclusively, this study demonstrates that inhibition of the Keap1/Nrf2 signaling pathway could significantly promote the incidence of T1DM. This study indicates that activation of Keap1/Nrf2 signaling in pancreatic β-cells may be a useful pharmacological strategy for the clinical prevention and treatment of T1DM.

Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis

ABSTRACT Colitis is characterized by colonic inflammation and impaired gut health. Both features aggravate obesity and insulin resistance. Host defense peptides (HDPs) are key regulators of gut homeostasis and generally malfunctioning in above-mentioned conditions. We aimed here to improve bowel function in diet-induced obesity and chemically induced colitis through daily oral administration of lysozyme, a well-characterized HDP, derived from Acremonium alcalophilum. C57BL6/J mice were fed either low-fat reference diet or HFD ± daily gavage of lysozyme for 12 weeks, followed by metabolic assessment and evaluation of colonic microbiota encroachment. To further evaluate the efficacy of intestinal inflammation, we next supplemented chow-fed BALB/c mice with lysozyme during Dextran Sulfate Sodium (DSS)-induced colitis in either conventional or microbiota-depleted mice. We assessed longitudinal microbiome alterations by 16S amplicon sequencing in both models. Lysozyme dose-dependently alleviated intestinal inflammation in DSS-challenged mice and further protected against HFD-induced microbiota encroachment and fasting hyperinsulinemia. Observed improvements of intestinal health relied on a complex gut flora, with the observation that microbiota depletion abrogated lysozyme’s capacity to mitigate DSS-induced colitis. Akkermansia muciniphila associated with impaired gut health in both models, a trajectory that was mitigated by lysozyme administration. In agreement with this notion, PICRUSt2 analysis revealed specific pathways consistently affected by lysozyme administration, independent of vivarium, disease model and mouse strain. Taking together, lysozyme leveraged the gut microbiota to curb DSS-induced inflammation, alleviated HFD-induced gastrointestinal disturbances and lowered fasting insulin levels in obese mice. Collectively, these data present A. alcalophilum-derived lysozyme as a promising candidate to enhance gut health.

Demographic, Clinical and Biochemical Characteristics of Pediatric Obesity: Interim Analysis of a Larger Prospective Study.

Pediatric obesity is a common nutritional disorder that affects more than a third of the young population and predis-poses individuals to greater future morbidity and mortality.Materials and methods: Sixty-two children were recruited in the study. Demographic and clinical information regarding the pa-tients and their parents was collected. Data about the weight, height, systolic (SP) and diastolic (DP) blood pressure, lipid metabolic profile, thyroid hormone levels, glucose and insulin levels before and after oral glucose tolerance test (OGTT) of participants were also collected. Body mass index (BMI) was calculated and patients were classified into groups according to the International Obesity Task Force criteria. Descriptive, comparative parametric, non-parametric tests and Spearman's ranked correlations were used in the statistical analysis.Results: The study sample consisted of 34 males and 28 females aged 11.6 and 11.8 years, respectively (p=0.781). The mean BMI was 30.5 (SD 5.5): 8 of participant had normal weight (≤25 BMI), 22 were overweight (25-30 BMI), and 32 were obese (≥30 BMI). The chil-dren's BMIs were significantly associated with parental BMIs (r=0.395, p=0.004). Both SP and DP were significantly different between BMI subgroups (p=0.005 and p=0.001, respectively) with the obese group having the highest values (post-hoc Benjamini, p=0.004). Obese children had lower average T4 levels when compared to the comparators (7.5 µg/dL vs. 9.9 µg/dL, p=0.021). Obese children had significantly lower baseline glucose levels and higher insulin levels when compared to the overweight/normal BMI children (73.8 mg/dL vs. 86.4 mg/dL, p.

Dynamic folding modulation generates FGF21 variant against diabetes.

Fibroblast growth factor 21 (FGF21) is a regulator of glucose and lipid metabolism. It has been widely considered as a promising candidate for the treatment of type 2 diabetes mellitus (T2DM) and other related metabolic disorders. However, lack of structural and dynamic information has limited FGF21-based drug development. Here, using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of FGF21 and find that its non-canonical flexible β-trefoil conformation affects the folding of β2-β3 hairpin and further overall protein stability. To modulate folding dynamics, we designed an FGF21-FGF19 chimera, FGF21SS . As expected, FGF21SS shows better thermostability without inducing hepatocyte proliferation. Functional characterization of FGF21SS shows its better insulin sensitivity, reduced inflammation in 3T3-L1 adipocytes, and lower blood glucose and insulin levels in ob/ob mice compared with wild type. Our dynamics-based rational design provides a promising approach for FGF21-based therapeutic development against T2DM.

Acute metabolic effects of melatonin-A randomized crossover study in healthy young men.

Melatonin regulates circadian rhythm, but may also have effects on glucose homeostasis. A common G-allele in the MTNR1B locus has been associated with an increased risk of type 2 diabetes (T2DM). We aimed to examine acute effects of high doses of melatonin on glucose metabolism with attention to MTNR1B genotype. Twenty men were examined in a double-blinded, randomized crossover study on two nonconsecutive days with four doses of 10mg oral melatonin or placebo. Insulin sensitivity and insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic-euglycaemic clamp (HEC). Blood samples were drawn to determine the metabolic profile and MTNR1B rs10830963 genotype. Indirect calorimetry and blood pressure measurements were also performed. Insulin sensitivity index was significantly reduced on the melatonin day (P=.028) in the whole group and in homozygous carriers of the rs10830963 C-allele (P=.041). Glucose during the IVGTT was unaffected, but there was a tendency towards lower insulin and C-peptide levels in the first minutes after glucose administration in G-allele carriers. Systolic blood pressure decreased and lipid oxidation increased significantly on the melatonin day in rs10830963 G-allele carriers. Overall, our study reports that acute administration of melatonin in supra-physiological doses may have a negative impact on insulin sensitivity. Clinical trial registration number (clinicaltrial.gov): NCT03204877.

Metformin and ovarian cancer: the evidence.

In recent decades, great interest in the off-label use of metformin has arisen as a result of its broad effects on different signaling pathways, with only a few side effects, and low cost. Metformin has been shown to have multiple, dose-dependent preclinical anticancer effects, which can be roughly divided into either direct effects via inhibition of mitochondrial respiratory chain complex I, or indirect effects through lowered glucose, insulin and insulin-like growth factor levels. Further details on in vitro and in vivo anticancer effects specifically in ovarian cancer are continuously reported. Preclinically metformin has clear chemosensitizing effects in ovarian cancer and it is an effective negative regulator of angiogenesis. There are also some epidemiological studies on metformin use in ovarian cancer, but the results of these studies are not as promising as those preclinical studies would indicate. Most preclinical studies have involved metformin concentrations that are many times higher than the pharmacological doses used in patients, which might confound the clinical use of metformin as regards the above-mentioned aspects. In this review we evaluate preclinical and clinical evidence concerning metformin in ovarian cancer treatment.

A giant pelvic solitary fibrous tumor with Doege\u2013Potter syndrome successfully treated with transcatheter arterial embolization followed by surgical resection: a case report

BackgroundSolitary fibrous tumor (SFT), a mesenchymal fibroblastic tumor with a hypervascular nature, rarely develops in the pelvis. Resection of a giant SFT occupying the pelvic cavity poses an increased risk of developing massive hemorrhage during resection, although surgical resection is the most effective treatment method for this tumor to achieve a potential cure. SFT rarely develops with Doege–Potter syndrome, which is known as a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia (NICTH) secondary to SFT that secretes insulin-like growth factor-II (IGF-II). We present a case of a giant pelvic SFT with Doege–Potter syndrome, which was successfully treated with transcatheter arterial embolization (TAE) followed by surgical resection.Case presentationA 46-year-old woman presented with a disorder of consciousness due to refractory hypoglycemia. Images of the pelvis showed a giant and heterogeneously hypervascular mass displacing and compressing the rectum. Endocrinological evaluation revealed low serum levels of insulin and C-peptide consistent with NICTH. Angiography identified both the inferior mesenteric artery and the bilateral internal iliac artery as the main feeders of the tumor. To avoid intraoperative massive bleeding, super-selective TAE was performed for the tumor 2 days prior to surgery. Hypoglycemia disappeared after TAE. The tumor was resected completely, with no massive hemorrhage during resection. Histologically, it was diagnosed as IGF-II-secreting SFT. Partial necrosis of the rectum in the specimen was observed due to TAE. The patient was followed up for 2 years and no evidence of disease has been reported.ConclusionsPreoperative angiography followed by TAE is an exceedingly helpful method to reduce intraoperative hemorrhage when planning to resect SFT occupying the pelvic cavity. Complications related to ischemia should be kept in mind after TAE, which needs to be planned within 1 or 2 days before surgery. TAE for tumors may be an option in addition to medical and surgical treatment for persistent hypoglycemia in Doege–Potter syndrome.