scholarly journals Are There Sex Differences in the Reaction of Undercarboxylated Osteocalcin to Hypoglycemia?

2020 ◽  
pp. S315-S320
Author(s):  
M. DUŠKOVÁ ◽  
L. KOLÁTOROVÁ ◽  
H. JANDÍKOVÁ ◽  
H. POSPÍŠILOVÁ ◽  
L. STÁRKA
Keyword(s):  
Glucose Metabolism ◽  
Tolerance Test ◽  
Undercarboxylated Osteocalcin ◽  
New Bone Formation ◽  
Time Intervals ◽  
Insulin Tolerance ◽  
Interesting Difference ◽  
Regular Time ◽  
Endocrine Organs

There has been increasing evidence in recent years for the hypothesis of bones as endocrine organs. Osteocalcin, long considered just a marker of new bone formation, is now seen as the first hormone produced by bones, and seems to be associated with regulating glucose metabolism and reproduction. The aim of this work was to monitor changes of osteocalcin in reaction to hypoglycemia, and determine if there are differences in such reactions between the sexes. The study included 61 healthy probands with physiological calciophosphate metabolism (30 men and 31 women). We applied to each of them an insulin tolerance test, and then monitored levels of undercarboxylated osteocalcin and reactions to hypoglycemia at regular time intervals. We found differences in the reaction to hypoglycemia between the sexes. In men there was a significant decline in undercarboxylated osteocalcin between the 30 and 40 min (p<0.0015), which reflects a reaction to a glycemic decline between 25-30 min, followed by reversal. Low undercarboxylated osteocalcin in men lasted up to 90 min, after which they returned to levels before the test. In women we did not find any significant changes in undercarboxylated osteocalcin levels. Changes in undercarboxylated osteocalcin induced by hypoglycemia indicate a relationship between bones and glucose metabolism. There was an interesting difference between the sexes. However, a definitive conclusion about the role of osteocalcin in human metabolism will require numerous future studies.

scholarly journals TNF signaling impacts glucagon-like peptide-1 expression and secretion

2018 ◽  
Vol 61 (4) ◽  
pp. 153-161 ◽  
Author(s):  
Sufang Chen ◽  
Wei Wei ◽  
Minjie Chen ◽  
Xiaobo Qin ◽  
Lianglin Qiu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Deficient Mice

Numerous studies have implicated tumor necrosis factor α (TNFα) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNFα, lymphotoxin α (LTα) binds to and activates TNFR1. Thus, TNFα and LTα together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1-deficient mice (TNFR1−/−), TNFα/LTα/LTβ triple-deficient mice (TNF/LT∆3) and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test and oral glucose tolerance test. The present results showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had comparable body weight, tolerance to intraperitoneal glucose and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.

Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function

2006 ◽  
Vol 387 (4) ◽  
pp. 431-436 ◽  
Author(s):  
Ronaldo C. Araújo ◽  
Marcelo A. Mori ◽  
Vanessa F. Merino ◽  
Jean-Loup Bascands ◽  
Joost P. Schanstra ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Insulin Release ◽  
Serine Proteases ◽  
Tolerance Test ◽  
B1 Receptor ◽  
Subtype B ◽  
Insulin Tolerance ◽  
Kinin B1 Receptor ◽  
And Control

Abstract Kinins are potent vasoactive peptides generated in blood and tissues by the kallikrein serine proteases. Two distinct kinin receptors have been described, one constitutive (subtype B2) and one inducible (subtype B1), and many physiological functions have been attributed to these receptors, including glucose homeostasis and control of vascular permeability. In this study we show that mice lacking the kinin B1 receptor (B1 -/- mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B1 -/- mice also present pancreas abnormalities, characterized by fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia and reduced insulin release after a glucose load. Nevertheless, an insulin tolerance test indicated higher sensitivity in B1 -/- mice. In line with this phenotype, pancreatic vascular permeability was shown to be reduced in B1 receptor-ablated mice. The B1 agonist desArg9bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B1 -/- mice or in isolated islets. Our data demonstrate the importance of the kinin B1 receptor in the control of pancreatic vascular homeostasis and insulin release, highlighting a new role for this receptor in the pathogenesis of diabetes and related diseases.

scholarly journals Effect of Forskolin on Body Weight, Glucose Metabolism and Adipocyte Size of Diet-Induced Obesity in Mice

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 645
Author(s):  
Jing-Yi Chen ◽  
Shao-Yu Peng ◽  
Yeong-Hsiang Cheng ◽  
I-Ta Lee ◽  
Yu-Hsiang Yu
Keyword(s):  
Body Weight ◽  
Glucose Metabolism ◽  
Dimethyl Sulfoxide ◽  
High Fat Diet ◽  
Tolerance Test ◽  
Cell Diameter ◽  
High Fat ◽  
Fat Cell ◽  
Glucose Levels ◽  
Insulin Tolerance

The purpose of this study was to investigate the effects of forskolin on body weight, glucose metabolism and fat cell diameter in high-fat diet-induced obese mice. Four-week-old male mice (C57BL/6) were randomly assigned to 1 of 3 treatment groups: a high-fat diet plus 5% dimethyl sulfoxide (vehicle), high-fat diet plus 2 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide) and high-fat diet plus 4 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide). Forskolin or dimethyl sulfoxide was administered intraperitoneally every two days. The results indicated that no significant difference was observed in the body weight, feed intake and serum lipid parameters among groups at 20 weeks of age. The blood glucose levels were significantly reduced in the groups treated with 2 mg/kg of forskolin before glucose tolerance test. Forskolin administration linearly decreased blood glucose levels of high-fat diet-fed mice at 90 min and total area under curve (AUC) after insulin tolerance test. The subcutaneous adipocyte diameter was significantly reduced in the groups treated with 2 mg/kg of forskolin. Forskolin administration linearly reduced the gonadal adipocyte diameter of high-fat diet-fed mice. Forskolin significantly reduced the differentiation of murine mesenchymal stem cells into adipocytes and this was accompanied by a decrease in intracellular triglyceride content and an increase in glycerol concentration in the culture medium. The subcutaneous adipocyte diameter, gonadal adipocyte diameter and total AUC of insulin tolerance test were moderately negatively correlated with the concentration of forskolin in the high-fat diet-induced obese model. These results demonstrate that forskolin can regulate glucose metabolism and reduce fat cell diameter of high-fat diet-fed mice and inhibit the adipocyte differentiation of murine mesenchymal stem cells.

scholarly journals The Role of Bone Morphogenetic Protein 9 in Nonalcoholic Fatty Liver Disease in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Qin-Juan Sun ◽  
Ling-Yan Cai ◽  
Jie Jian ◽  
Ya-Lu Cui ◽  
Chen-Kai Huang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Fatty Liver Disease ◽  
Mouse Liver ◽  
Tolerance Test ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
Nonalcoholic Fatty Liver ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 9

Background and Aims: It’s reported that bone morphogenetic protein 9 (BMP9) played an important role in lipid and glucose metabolism, but the role of BMP9 in nonalcoholic fatty liver disease (NAFLD) is unclear. Here, we evaluated the therapeutic efficacy of recombined BMP9 in NAFLD mice and investigated the potential mechanism.Methods: The effects of recombinant BMP9 on NAFLD were assessed in HFD-induced NAFLD mice. C57BL/6 mice were administrated with high-fat diet (HFD) for 12 weeks. In the last 4 weeks, mice were treated with PBS or recombined BMP9 once daily. Insulin sensitivity was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT) at the end of the 12th week. Then NAFLD related indicators were assessed by a variety of biological methods, including histology, western blotting, real-time PCR, RNA-seq and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses.Results: BMP9 reduced obesity, improved glucose metabolism, alleviated hepatic steatosis and decreased liver macrophages infiltration in HFD mice. RNA-seq showed that Cers6, Cidea, Fabp4 involved in lipid and glucose metabolism and Fos, Ccl2, Tlr1 involved in inflammatory response downregulated significantly after BMP9 treatment in HFD mouse liver. ATAC-seq showed that chromatin accessibility on promoters of Cers6, Fabp4, Ccl2 and Fos decreased after BMP9 treatment in HFD mouse liver. KEGG pathway analysis of dysregulated genes in RNA-seq and integration of RNA-seq and ATAC-seq showed that TNF signaling pathway and Toll-like receptor signaling pathway decreased in BMP9 treated HFD mouse liver.Conclusion: Our data revealed that BMP9 might alleviate NAFLD via improving glucose and lipid metabolism, decreasing inflammatory response and reshaping chromatin accessibility in HFD mouse liver. BMP9 downregulate genes related to lipid metabolism, glucose metabolism and inflammation expression, at least partially via decreasing promoter chromatin accessibility of Cers6, Fabp4, Fos and Tlr1. BMP9 may also reduce the expression of liver Ccl2, thereby changing the number or composition of liver macrophages, and ultimately reducing liver inflammation. The effect of BMP9 on NAFLD might be all-round, and not limit to lipid and glucose metabolism. Therefore, the underlying mechanism needs to be studied in detail further.

scholarly journals SUN-261 Deletion of Hepatic Kisspeptin Results in Abnormal Glucose Metabolism in Female Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Bahaa Aloqaily ◽  
Hyokjoon Kwon ◽  
Ariel L Negron ◽  
Fredric E Wondisford ◽  
Sally Radovick
Keyword(s):  
Gene Expression ◽  
Glucose Metabolism ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Peripheral Tissues ◽  
Male And Female ◽  
Female Mice ◽  
Qrt Pcr ◽  
Insulin Tolerance ◽  
Estrous Cyclicity

Abstract Kisspeptin is a hypothalamic protein critical for neuroendocrine control of pubertal development and fertility and is modulated by nutritional signals. Kisspeptin has been localized to specific neurons located in the arcuate and anteroventral periventricular (AVPV) nuclei of the hypothalamus and is secreted to control GnRH mediated pubertal maturation and reproduction. Kisspeptin has also been localized to peripheral tissues including the liver, fat, gonads, intestine and placenta, although its role in these tissues is unclear. The objective of current study is to define the role of hepatic kisspeptin as a metabolic sensor. A floxed Kiss1 mouse has been developed, and ablation of liver-specific Kiss1 was achieved in two to three month old Kiss1f/f male and female mice given a single tail vein injection of thyroid hormone-binding globulin (TBG) promoter-driven Cre recombinase adeno-associated virus (AAV-CRE). A control group of Kiss1f/f male and female mice received an injection of AAV-GFP, expressing green fluorescent protein. Two weeks after injection, a glucose tolerance test (GTT) was performed followed by an insulin tolerance test. To determine whether changes had occurred in the reproductive axis, estrous cyclicity was assessed by daily vaginal smears and estrous cycle phases determined by vaginal cytology. Mice were euthanized four weeks post-injection and tissues were collected for RNA extraction and gene expression analysis via qRT-PCR. As expected, qRT-PCR data showed absence of Kiss1 expression in the liver of AAV-CRE mice compared to AAV-GFP mice with no changes in kisspeptin gene expression were noted in the ovary, testes, spleen, pancreas, arcuate or AVPV. Estrous cyclicity was also not affected by viral ablation of hepatic Kiss1. Elevated fasting glucose and glucose intolerance in the GTT were found in AAV-CRE compared to AAV-GFP females (P &lt; 0.05). No differences in AAV-CRE and AAV-GFP male mice were found, indicating the importance of Kiss1 in glucose homeostasis in females. The insulin tolerance test was not statistically different between groups or treatments. Further research is required to elucidate the mechanism by which hepatic kisspeptin alters glucose metabolism in mice in a sexually-dimorphic fashion.

scholarly journals miR-22-3p is involved in gluconeogenic pathway modulated by 3,5-diiodo-L-thyronine (T2)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rosalba Senese ◽  
Federica Cioffi ◽  
Giuseppe Petito ◽  
Pieter de Lange ◽  
Aniello Russo ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Tolerance Test ◽  
High Fat ◽  
Beneficial Effects ◽  
Insulin Tolerance

Abstract The 3,5-diiodo-L-thyronine (T2) has emerged as an active iodothyronine and its beneficial effects on glucose metabolism including glucose tolerance and insulin resistance is well established. However, little is known about its molecular mechanisms. Given the emerging importance of microRNAs in various metabolic diseases, in this study a possible link between the effects of T2 on glucose metabolism and miRNA expression was investigated by using an in vivo model in which T2 was administered in rats receiving a high fat diet, a condition known to impair glucose homeostasis. The results showed that T2-treated rats had a better tolerance to glucose load and a better performance at the insulin tolerance test in comparison to high fat diet animals. Interestingly, in the serum of the animals treated with T2 there was a general decrease of miRNAs with miR-22a-3p, miR-34c-5p and miR-33a-3p significantly downregulated. Furthermore, miR-22a-3p had the largest variation pointing toward its preeminent role in T2 metabolic effect. In fact, in liver there was an up-regulation of its target (Transcription Factor 7) Tcf7, which had an important impact on gluconeogenesis. This study provide, for the first time, evidences that miRNAs are involved in the effects exerted by T2 on glucose homeostasis.

scholarly journals Up-Regulating the Heme Oxygenase System with Hemin Improves Insulin Sensitivity and Glucose Metabolism in Adult Spontaneously Hypertensive Rats

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 549-560 ◽  
Author(s):  
Joseph Fomusi Ndisang ◽  
Nina Lane ◽  
Noor Syed ◽  
Ashok Jadhav
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Essential Hypertension ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Tolerance Test ◽  
Spontaneously Hypertensive ◽  
Insulin Tolerance

Accumulating clinical evidence indicates that impaired glucose tolerance is a common phenomenon in essential hypertension. Although recent evidence underscores the role of heme-oxygenase (HO) in diabetes, its effects on insulin sensitivity and glucose metabolism in spontaneously hypertensive rat (SHR), a model of essential hypertension with characteristics of metabolic syndrome including insulin resistance/impaired glucose metabolism remains largely unclear. Here we report the effects of the HO inducer, hemin, and the HO blocker, chromium-mesoporphyrin on insulin sensitivity and glucose metabolism in SHRs. Adult SHRs were severely hypertensive but normoglycemic. Hemin therapy lowered blood pressure, increased plasma insulin, decreased glycemia, and enhanced insulin sensitivity by improving glucose tolerance (ip glucose tolerance test) and insulin tolerance (ip insulin tolerance test) but reduced insulin resistance (homeostasis model assessment index). These effects were accompanied by increased gastrocnemius muscle HO-1, HO activity, cGMP, cAMP alongside antioxidants including bilirubin, ferritin, superoxide dismutase, catalase, and the total antioxidant capacity, whereas oxidative/inflammatory mediators like 8-isoprostance, nuclear-factor-κB, activating-protein-1, activating-protein-2, c-Jun-NH2-terminal-kinase, and heme were abated. Furthermore, hemin reduced proteinuria/albuminuria and enhanced the depressed levels of adiponectin, AMP-activated protein-kinase, and glucose transporter-4 in SHRs, suggesting that although SHRs are normoglycemic, insulin signaling and renal function may be impaired. Contrarily, the HO inhibitor chromium-mesoporphyrin exacerbated oxidative stress, aggravated insulin resistance, glucose tolerance, insulin tolerance and nephropathy. Hemin also enhanced HO signaling in Wistar Kyoto and Sprague Dawley rats and increased insulin sensitivity albeit less intensely than in SHRs, suggesting greater selectivity of HO in SHRs with dysfunctional insulin signaling. These results suggest that perturbations of insulin signaling may be a forerunner to hyperglycemia in essential hypertension. By concomitantly potentiating insulin-sensitizing agents, suppressing insulin/glucose intolerance, and abating oxidative stress, HO inducers may prevent metabolic and cardiovascular complications in essential hypertension.

Nocturnal levels of chemerin and progranulin in adolescents: influence of sex, body mass index, glucose metabolism and sleep

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Johann Daxer ◽  
Theresa Herttrich ◽  
Ying Y. Zhao ◽  
Mandy Vogel ◽  
Andreas Hiemisch ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Normal Weight ◽  
Sleep Stages ◽  
Oral Glucose ◽  
Study Cohort ◽  
Sleep Regulation ◽  
Child Study

AbstractBackground:Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism.Methods:The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort. We obtained longitudinal serum adipokine levels during in-laboratory polysomnography followed by an oral glucose tolerance test.Results:Overweight/obese adolescents had significantly higher mean nocturnal serum chemerin area under the curve (AUC) levels (348.2±133.3 vs. 241.7±67.7 vs. ng/mL×h, p<0.001) compared to normal-weight controls. In detail, higher chemerin AUC levels in obese/overweight subjects were exclusively due to increased levels in females. No overall difference for serum progranulin AUC was found between the groups. However, when assessing sex-specific levels, serum progranulin AUC levels were ~30% higher in overweight/obese males compared to overweight/obese females. Of note, nocturnal serum chemerin and progranulin AUC did not exhibit a correlation with markers of glucose metabolism or sleep stages.Conclusions:Collectively, we report a sexual dimorphism in nocturnal progranulin and chemerin levels, which may help explain underlying differences in energy balance and body composition between males and females in the context of obesity.

scholarly journals Insulin Resistance in Apolipoprotein M Knockout Mice is Mediated by the Protein Kinase Akt Signaling Pathway

2020 ◽  
Vol 20 (5) ◽  
pp. 771-780
Author(s):  
Shuang Yao ◽  
Jun Zhang ◽  
Yuxia Zhan ◽  
Yuanping Shi ◽  
Yang Yu ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Differentially Expressed ◽  
Insulin Stimulation ◽  
Apolipoprotein M ◽  
Insulin Tolerance ◽  
Protein Kinase Akt

Background: Previous clinical studies have suggested that apolipoprotein M (apoM) is involved in glucose metabolism and plays a causative role in insulin sensitivity. Objective: The potential mechanism of apoM on modulating glucose homeostasis is explored and differentially expressed genes are analyzed by employing ApoM deficient (ApoM-/- ) and wild type (WT) mice. Methods: The metabolism of glucose in the hepatic tissues of high-fat diet ApoM-/- and WT mice was measured by a glycomics approach. Bioinformatic analysis was applied for analyzing the levels of differentially expressed mRNAs in the liver tissues of these mice. The insulin sensitivity of ApoM-/- and WT mice was compared using the insulin tolerance test and the phosphorylation levels of protein kinase Akt (AKT) and insulin stimulation in different tissues were examined by Western blot. Results: The majority of the hepatic glucose metabolites exhibited lower concentration levels in the ApoM-/- mice compared with those of the WT mice. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that ApoM deficiency affected the genes associated with the metabolism of glucose. The insulin tolerance test suggested that insulin sensitivity was impaired in ApoM-/- mice. The phosphorylation levels of AKT in muscle and adipose tissues of ApoM-/- mice were significantly diminished in response to insulin stimulation compared with those noted in WT mice. Conclusion: : ApoM deficiency led to the disorders of glucose metabolism and altered genes related to glucose metabolism in mice liver. In vivo data indicated that apoM might augment insulin sensitivity by AKT-dependent mechanism.

Sign in / Sign up

Export Citation Format

Share Document