Fasting Blood Glucose In Mice Research Articles

Bedding as a variable affecting fasting blood glucose and vascular physiology in mice.

Rodent husbandry requires careful consideration of environmental factors that may impact colony performance and subsequent physiological studies. Of note, recent reports have suggested corncob bedding may affect a broad range of organ systems. As corncob bedding may contain digestible hemicelluloses, trace sugars, and fiber, we hypothesized that corncob bedding impacts overnight fasting blood glucose and murine vascular function. Here, we compared mice housed on corncob bedding, which were then fasted overnight on either corncob or ALPHA-dri bedding, a virgin paper pulp cellulose alternative. Male and female mice were used from two noninduced, endothelial-specific conditional knockout strains [Cadherin 5-cre/ERT2, floxed hemoglobin-α1 (Hba1fl/fl) or Cadherin 5-cre/ERT2, floxed cytochrome-B5 reductase 3 (CyB5R3fl/fl)] on a C57BL/6J genetic background. After fasting overnight, initial fasting blood glucose was measured, and mice were anesthetized with isoflurane for measurement of blood perfusion via laser speckle contrast analysis using a PeriMed PeriCam PSI NR system. After a 15-min equilibration, the mice were injected intraperitoneally with the α1-adrenergic receptor agonist, phenylephrine (5 mg/kg), or saline, and monitored for changes in blood perfusion. After a 15-min response period, blood glucose was remeasured postprocedure. In both strains, mice fasted on corncob bedding had higher blood glucose than the pulp cellulose group. In the CyB5R3fl/fl strain, mice housed on corncob bedding displayed a significant reduction in phenylephrine-mediated change in perfusion. In the Hba1fl/fl strain, phenylephrine-induced change in perfusion was not different in the corncob group. This work suggests that corncob bedding, in part due to its ingestion by mice, could impact vascular measurements and fasting blood glucose. To promote scientific rigor and improve reproducibility, bedding type should be routinely included in published methods.NEW & NOTEWORTHY This study demonstrates real-time measurement of changes in perfusion to pharmacological treatment using laser speckle contrast analysis. Furthermore, this investigation revealed that fasting mice overnight on corncob bedding has differential effects on vascular function and that there was increased fasting blood glucose in mice fasted on corncob bedding compared with paper pulp cellulose bedding. This highlights the impact that bedding type can have on outcomes in vascular and metabolic research and reinforces the need for thorough and robust reporting of animal husbandry practices.

Corncob bedding alters fasting blood glucose and vascular function in mice

Rodent husbandry requires careful consideration of environmental factors that may impact colony performance and subsequent physiological studies. Of note, recent reports have suggested corncob bedding is potentially a confounding variable affecting a broad range of organ systems. As corncob bedding may contain digestible hemicelluloses, trace sugars, and fiber, we hypothesized that corncob bedding impacts murine vascular function and overnight fasting blood glucose. Here, we compared mice housed on corncob bedding, which were then fasted overnight on either corncob or ALPHA-dri bedding, a paper cellulose alternative. Male and female mice were used from two non-induced, endothelial-specific conditional knock-out strains (Cadherin 5-CreERT2, floxed hemoglobin alpha 1 [Hba1] or Cadherin 5-CreERT2, floxed cytochrome B5 reductase 3 [CyB5R3]) on a C57BL/6J genetic background. After fasting overnight, initial blood glucose was measured, and mice were anesthetized with isoflurane for measurement of blood perfusion via laser speckle contrast analysis using a PeriMed PeriCam PSI NR system. After a 15-minute equilibration, the mice were injected intraperitoneally with phenylephrine (5 mg/kg) or saline and monitored for changes in blood perfusion. After a 15-minute response period, blood glucose was remeasured post-procedure. Consistently, mice fasted on corncob bedding had higher blood glucose than the ALPHA-dri group. In the CyB5R3 strain, corncob bedding caused a reduction in phenylephrine-mediated vasoconstriction. In the Hba1 strain, phenylephrine-induced vasoconstriction was more variable in the corncob group. Altogether, this work suggests that corncob bedding could be a confounding variable for vascular measurements and fasting blood glucose in mice. To promote scientific rigor and improve reproducibility, bedding type should be included in published methods. NIH R01HL155618 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Therapeutic Effect of Coriolus versicolor Fruiting Body on STZ-Induced ICR Diabetic Mice.

Coriolus versicolor is a natural drugs which has many pharmacological effects such as antitumor and enhanced immune activity. This paper studies the therapeutic effect of Coriolus versicolor fruiting body (CVFB) on streptozotocin (STZ)-induced Institute of Cancer Research (ICR) diabetic mice, the STZ solution was administered intraperitoneally at a dose of 150 mg/kg after fasting the mice, and ICR mice with fasting blood glucose >16.7 mmol/l were selected for research. Metformin was the positive control, and the dose of CVFB powder (1000 mg/kg, 2000 mg/kg, and 4000 mg/kg) for 28 consecutive days by gavage. The serum and liver of mice were collected for relevant index content testing. The results showed that CVFB can control or reduce the fasting blood glucose of mice and accelerate the rate of glucose metabolism, can reduce the levels of total cholesterol (T-CHO), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in mice, and regulate the abnormal symptoms of blood lipid metabolism commonly found in diabetes. It can increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) antioxidant enzymes and enhance the ability of antioxidative stress in diabetic mice. In the H&E staining and apoptosis experiments of pancreatic tissue, CVFB can greatly reduce the inflammatory factors present in islets, increase the islet cells, and reduce the apoptotic rate caused by diabetes. All data confirmed the therapeutic effect of CVFB on diabetic ICR mice. The present study provides a scientific basis for the development of drugs for the prevention and treatment of diabetes, it is of great significance to the in-depth study of Coriolus versicolor.

MLR-1023 Treatment in Mice and Humans Induces a Thermogenic Program, and Menthol Potentiates the Effect.

A glucose-lowering medication that acts by a different mechanism than metformin, or other approved diabetes medications, can supplement monotherapies when patients fail to meet blood glucose goals. We examined the actions underlying the effects of an insulin sensitizer, tolimidone (MLR-1023) and investigated its effects on body weight. Diet-induced obesity (CD1/ICR) and type 2 diabetes (db/db) mouse models were used to study the effect of MLR-1023 on metabolic outcomes and to explore its synergy with menthol. We also examined the efficacy of MLR-1023 alone in a clinical trial (NCT02317796), as well as in combination with menthol in human adipocytes. MLR-1023 produced weight loss in humans in four weeks, and in mice fed a high-fat diet it reduced weight gain and fat mass without affecting food intake. In human adipocytes from obese donors, the upregulation of Uncoupling Protein 1, Glucose (UCP)1, adiponectin, Glucose Transporter Type 4 (GLUT4), Adipose Triglyceride Lipase (ATGL), Carnitine palmitoyltransferase 1 beta (CPT1β), and Transient Receptor Potential Melastin (TRPM8) mRNA expression suggested the induction of thermogenesis. The TRPM8 agonist, menthol, potentiated the effect of MLR-1023 on the upregulation of genes for energy expenditure and insulin sensitivity in human adipocytes, and reduced fasting blood glucose in mice. The amplification of the thermogenic program by MLR-1023 and menthol in the absence of adrenergic activation will likely be well-tolerated, and bears investigation in a clinical trial.

FXR activation alleviates tacrolimus-induced post-transplant diabetes mellitus by regulating renal gluconeogenesis and glucose uptake

BackgroundTacrolimus (FK506)-induced diabetes mellitus is one of the most important factors of post-transplant diabetes mellitus (PTDM). However, the detailed mechanisms underlying PTDM are still unclear. Farnesoid X receptor (FXR) regulates glycolipid metabolism. The objective of this study was to explore whether FXR is involved in the development of tacrolimus-induced diabetes mellitus.MethodsAfter C57BL/6J mice were treated with tacrolimus (FK506) for 3 months, the fasting blood glucose levels, body weights, renal morphological alterations, and mRNA expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2) among the control group, the FK506 group and the FK506 + GW4064 (a FXR agonist) group (n = 7) were measured. The intracellular location of peroxisome proliferator activated receptor γ coactivator-1α (PGC1α) and forkhead box O1 (FOXO1) was detected by immunofluorescence. Human renal cortex proximal tubule epithelial cells (HK-2) were treated with 15 μM FK506 or 4 μM FXR agonist (GW4064) for 24, 48 and 72 h, and the expression levels of FXR, gluconeogenesis and glucose uptake, representing the enzymes PEPCK and GLUT2, were detected with real-time PCR and western blot analyses. Finally, the mRNA levels of PEPCK and GLUT2 in HK-2 cells were measured after FXR was upregulated.ResultsFK506 significantly inhibited the mRNA and protein levels of FXR at 48 h and 72 h in HK-2 cells (P < 0.05). Meanwhile, FK506 promoted gluconeogenesis and inhibited glucose uptake in HK-2 cells (P < 0.05). However, overexpression of FXR in transfected HK-2 cell lines significantly inhibited gluconeogenesis and promoted glucose uptake (P < 0.05). The FXR agonist GW4064 significantly decreased the fasting blood glucose in mice challenged with FK506 for 3 months (P < 0.05), inhibited gluconeogenesis (P < 0.05) and significantly promoted glucose uptake (P < 0.05). Immunofluorescence staining and western blot analyses further revealed that FXR activation may affect the translocation of PGC1α and FOXO1 from the nucleus to the cytoplasm.ConclusionsFXR activation may mitigate tacrolimus-induced diabetes mellitus by regulating gluconeogenesis as well as glucose uptake of renal cortex proximal tubule epithelial cells in a PGC1α/FOXO1-dependent manner, which may be a potential therapeutic strategy for the prevention and treatment of PTDM.

Enrichment of total flavones and licochalcone A from licorice residues and its hypoglycemic activity

Industrial processing of glycyrrhizic leads to a lot of residues which are usually threw away randomly or used as feed. Therefore, the purpose of this study was to study licorice residues as a source of bioactive compounds with potentially applications. In this study, the enrichment and purification of total flavones from the licorice residues was achieved by using macroporous resins. The performances and separation characteristics of four selected macroporous resins with different chemical and physical properties were investigated. HPD-100 resin was the most effective, the content of total flavones increased from 50.94% in the original extract to 82.98% in the 80% ethanol fraction (a 1.63-fold increase). Further purification treatment by polyamide resin, licochalcone A with a purity of 80.28% was obtained in a 45% ethanol fraction, and a higher purity (>85%) of licochalcone A can be obtained by single crystallization operation. And hypoglycemic effect of the total flavones from licorice residues on high fat diet and STZ induced diabetic c57 mice was preliminary investigated. The results showed: the fasting blood glucose of mice in the low and medium dose total flavones group decreased significantly. The proposed technique is uncomplicated, easily managed, cost-effective, and environmentally friendly and is proper for both large-scale licorice residues application and waste management.

Purification and a molecular docking study of α-glucosidase-inhibitory peptides from a soybean protein hydrolysate with ultrasonic pretreatment

Soybean protein was hydrolyzed using trypsin with ultrasound pretreatment to obtain a soybean protein hydrolysate. The latter was separated sequentially by ultrafiltration, ion exchange chromatography, gel filtration chromatography, and reversed-phase high-performance liquid chromatography. A highly active component with molecular weight less than 5 kDa, obtained by ultrafiltration, significantly reduced the levels of fasting blood glucose in mice. α-Glucosidase-inhibitory activity of fraction C-III-2a separated by reversed-phase high-performance liquid chromatography was the highest, and the half-inhibitory concentration (IC50) was 0.049 mg/mL. Amino acid sequences of two tripeptides from fraction C-III-2a were identified as Gly-Ser-Arg and Glu-Ala-Lys by ion trap tandem mass spectrometry. Molecular docking analyses revealed that the α-glucosidase inhibition by the peptides could be mainly attributed to the formation of five strong hydrogen bonds between Glu-Ala-Lys and His-674, Asp-518, Arg-600, Asp-616, and Asp-282 in α-glucosidase, and to four hydrogen bonds between Gly-Ser-Arg and residues Asp-282, Asp-518, and Asp-616. The results indicated that an α-glucosidase-inhibitory peptide may have hypoglycemic efficacy when used as an ingredient in novel functional foods.

MicroRNA-219 decreases hippocampal long-term potentiation inhibition and hippocampal neuronal cell apoptosis in type 2 diabetes mellitus mice by suppressing the NMDAR signaling pathway.

Type 2 diabetes mellitus (T2DM) is a complex polygenic disease that causes hyperglycemia and accounts for 90%-95% of all diabetes mellitus cases. Hence, this study aimed to examine the effects of microRNA-219 (miR-219) on inhibition of long-term potentiation (LTP) and apoptosis of hippocampal neuronal cells in T2DM mice through the N-methyl-d-aspartate receptor (NMDAR) signaling pathway regulation. The T2DM mouse models were established, after which LTP in vivo was recorded by means of electrical biology, and the fasting blood glucose of mice was measured. Next, the density of pyramidal neurons in each group was calculated. Additionally, the expression levels of miR-219, the NMDAR signaling pathway [NMDAR1 (NR) 1, NR2A, and NR2B), downstream target proteins [calmodulin-dependent protein kinase-II (CaMK-II) and cAMP response element binding protein (CREB)], and apoptosis-related factors [Bcl2-associated X protein (Bax), c-caspase-9 and c-caspase-3] in the hippocampal tissues were determined. Finally, immunohistochemistry was applied to detect and measure the positive expression of Bax, caspase-9, and caspase-3 proteins. The results showed that upregulation of miR-219 increases LTP and density of pyramidal neurons in the hippocampal tissues of mice, while it decreases blood glucose of db/db mice. In addition, miR-219 upregulation also leads to decreased mRNA levels of NR1, NR2A, NR2B, CaMK-II, and CREB and protein levels of NR1, NR2A, NR2B, CaMK-II, CREB, p-CREB, Bax, c-caspase-9, and c-caspase-3. Furthermore, upregulation of miR-219 inhibits positive expression of Bax, caspase-9, and caspase-3 proteins, leading to the suppression of hippocampal neuronal cell apoptosis. The findings from this study indicated that the upregulation of miR-219 decreases LTP inhibition and hippocampal neuronal cell apoptosis in T2DM mice by downregulating the NMDAR signaling pathway, therefore suggesting that MiR-219 might be a future therapeutic strategy for T2DM.

Antidiabetic and Antiobesity Effects of Artemether in db/db Mice.

This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days. At the start and end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. We determined the serum insulin and glucagon levels by ELISA kits and calculated insulin resistance index (HOME-IR). HE staining was used to observe the morphologies of pancreas and liver in mice. The damage of pancreatic beta cells was evaluated by TUNEL staining and immunofluorescence. We found the following: (1) compared with the DM group, the food intake and weight increase rate of artemether group significantly reduced (P < 0.05); (2) compared with pretreatment, artemether significantly reduced the fasting blood glucose levels, and the areas under the curves (AUCs) of IPGTT were decreased significantly, increasing the tolerance to glucose of db/db mice. (P < 0.05); (3) artemether improved hyperinsulinemia and decreased the AUCs of IPITT and HOME-IR, increasing the insulin sensitivity of db/db mice. (4) Artemether significantly ameliorated islet vacuolar degeneration and hepatic steatosis in db/db mice. (5) Artemether reduced the apoptosis of pancreatic beta cells and increased insulin secretion in db/db mice compared with DM group (P < 0.05). Our results indicated that artemether significantly improved glucose homeostasis and insulin resistance and had the potential activity to prevent obesity, reduced the severity of fatty liver, and protected pancreatic beta cells, promising to treat type 2 diabetes.

A high isoflavone diet decreases 5′ adenosine monophosphate–activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice

Selenium (Se) has been implicated as a micronutrient that decreases adenosine monophosphate–activated protein kinase (AMPK) signaling and may increase diabetes risk by reducing insulin sensitivity. Soy isoflavones (IF) are estrogen-like compounds that have been shown to attenuate insulin resistance, hyperglycemia, adiposity, and increased AMPK activation. We hypothesized that a high IF (HIF) diet would prevent the poor metabolic profile associated with high Se intake. The purpose of this study was to examine changes in basal glucose metabolism and AMPK signaling in response to an HIF diet and/or supplemental Se in a mouse model. Male FVB mice were divided into groups receiving either a control diet with minimal IF (low IF) or an HIF diet. Each dietary group was further subdivided into groups receiving either water or Se at a dose of 3 mg Se/kg body weight daily, as Se-methylselenocysteine (SMSC). After 5 months, mice receiving SMSC had elevated fasting glucose (P < .05) and a tendency for glucose intolerance (P = .08). The increase in dietary IF did not result in improved fasting blood glucose. Interestingly, after 6 months, HIF-fed mice had decreased basal AMPK activation in liver and skeletal muscle tissue (P < .05). Basal glucose metabolism was changed by SMSC supplementation as evidenced by increased fasting blood glucose and glucose intolerance. High dietary IF levels did not protect against aberrant blood glucose. In FVB mice, decreased basal AMPK activation is not the mechanism through which Se exerts its effect. These results suggest that more research must be done to elucidate the role of Se and IF in glucose metabolism.

Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγ Pathway.

Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptor γ (PPARγ) transactivities and could decrease mRNA levels of PPARγ and its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγ and HMGCR signaling.