Regulation of liver glucokinase activity in rats with fructose-induced insulin resistance and impaired glucose and lipid metabolism

2009 ◽  
Vol 87 (9) ◽  
pp. 702-710 ◽  
Author(s):  
Flavio Francini ◽  
María C. Castro ◽  
Juan J. Gagliardino ◽  
María L. Massa
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Protein Concentration ◽  
Cytosolic Fraction ◽  
Liver Triglyceride ◽  
Glucose And Lipid Metabolism ◽  
Triglyceride Content

We evaluated the relative role of different regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2/FBPase-2), in liver glucokinase (GK) activity in intact animals with fructose-induced insulin resistance and impaired glucose and lipid metabolism. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content, GK activity, and GK and PFK2 protein and gene expression in fructose-rich diet (FRD) and control rats. After 3 weeks, FRD rats had significantly higher blood glucose, insulin and triglyceride levels, and liver triglyceride content, insulin resistance, and impaired glucose tolerance. FRD rats also had significantly higher GK activity in the cytosolic fraction (18.3 ± 0.35 vs. 11.27 ± 0.34 mU/mg protein). Differences in GK protein concentration (116% and 100%) were not significant, suggesting a potentially impaired GK translocation in FRD rats. Although GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals. PFK2 immunological blockage significantly decreased GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals. Under these conditions, PFK2 increase would be the main enhancer of GK activity.

scholarly journals Liraglutide Prevents Hypoadiponectinemia-Induced Insulin Resistance and Alterations of Gene Expression Involved in Glucose and Lipid Metabolism

2011 ◽  
Vol 17 (11-12) ◽  
pp. 1168-1178 ◽  
Author(s):  
Ling Li ◽  
Zongyu Miao ◽  
Rui Liu ◽  
Mengliu Yang ◽  
Hua Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Glucose And Lipid Metabolism

scholarly journals Dietary Genistein Could Modulate Hypothalamic Circadian Entrainment, Reduce Body Weight, and Improve Glucose and Lipid Metabolism in Female Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Liyuan Zhou ◽  
Xinhua Xiao ◽  
Qian Zhang ◽  
Jia Zheng ◽  
Ming Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Lipid Metabolism ◽  
Glucose Tolerance ◽  
Energy Intake ◽  
High Fat Diet ◽  
High Fat ◽  
Female Mice ◽  
Reduce Body Weight ◽  
Glucose And Lipid Metabolism

Genistein has beneficial effects on metabolic disorders. However, the specific mechanism is not clearly understood. In light of the significant role of the hypothalamus in energy and metabolic homeostasis, this study was designed to explore whether dietary genistein intake could mitigate the harmful effects of a high-fat diet on glucose and lipid metabolism and whether any alterations caused by dietary genistein were associated with hypothalamic gene expression profiles. C57BL/6 female mice were fed a high-fat diet without genistein (HF), a high-fat diet with genistein (HFG), or a normal control diet (CON) for 8 weeks. Body weight and energy intake were assessed. At the end of the study, glucose tolerance and serum levels of insulin and lipids were analyzed. Hypothalamic tissue was collected for whole transcriptome sequencing and reverse transcription quantitative PCR (RT-qPCR) validation. Energy intake and body weight were significantly reduced in the mice of the HFG group compared with those of the HF group. Mice fed the HFG diet had improved glucose tolerance and decreased serum triacylglycerol, free fatty acids, and low-density lipoprotein cholesterol compared with those fed the HF diet. The HFG diet also modulated gene expression in the hypothalamus; the most abundant genes were enriched in the circadian entrainment pathway. Dietary genistein intake could reduce body weight, improve glucose and lipid metabolism, and regulate hypothalamic circadian entrainment. The ability of genistein intake to influence regulation of the hypothalamic circadian rhythm is important since this could provide a novel target for the treatment of obesity and diabetes.

scholarly journals Differential hepatic gene expression in a polygenic mouse model with insulin resistance and hyperglycemia: evidence for a combined transcriptional dysregulation of gluconeogenesis and fatty acid synthesis

2004 ◽  
Vol 32 (1) ◽  
pp. 195-208 ◽  
Author(s):  
W Becker ◽  
R Kluge ◽  
T Kantner ◽  
K Linnartz ◽  
M Korn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Glucose Metabolism ◽  
Mrna Levels ◽  
Insulin Resistant ◽  
Glucose And Lipid Metabolism ◽  
Nzo Mice ◽  
Hepatic Glucose

New Zealand obese (NZO) mice exhibit severe insulin resistance of hepatic glucose metabolism. In order to define its biochemical basis, we studied the differential expression of genes involved in hepatic glucose and lipid metabolism by microarray analysis. NZOxF1 (SJLxNZO) backcross mice were generated in order to obtain populations with heterogeneous metabolism but comparable genetic background. In these backcross mice, groups of controls (normoglycemic/normoinsulinemic), insulin-resistant (normoglycemic/hyperinsulinemic) and diabetic (hyperglycemic/hypoinsulinemic) mice were identified. At 22 weeks, mRNA was isolated from liver, converted to cDNA, and used for screening of two types of cDNA arrays (high-density filter arrays and Affymetrix oligonucleotide microarrays). Differential gene expression was ascertained and assessed by Northern blotting. The data indicate that hyperinsulinemia in the NZO mouse is associated with: (i) increased mRNA levels of enzymes involved in lipid synthesis (fatty acid synthase, malic enzyme, stearoyl-CoA desaturase) or fatty acid oxidation (cytochrome P450 4A14, ketoacyl-CoA thiolase, acyl-CoA oxidase), (ii) induction of the key glycolytic enzyme pyruvate kinase, and (iii) increased mRNA levels of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects were enhanced by a high-fat diet. In conclusion, the pattern of gene expression in insulin-resistant NZO mice appears to reflect a dissociation of the effects of insulin on genes involved in glucose and lipid metabolism. The data are consistent with a hypothetical scenario in which an insulin-resistant hepatic glucose production produces hyperinsulinemia, and an enhanced insulin- and substrate-driven lipogenesis further aggravates the deleterious insulin resistance of glucose metabolism.

scholarly journals SAT-659 Micro/Nanoparticles from Antidiabetic Chinese Herbal Medicine Soup Increase Bioavailability of Phytochemicals and Regulate Glucose and Lipid Metabolism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lijing Ke ◽  
Pingfan Rao
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Blood Glucose ◽  
Herbal Medicine ◽  
Glucose Tolerance ◽  
Chinese Herbal Medicine ◽  
Therapeutic Effects ◽  
Chinese Herbal ◽  
Glucose And Lipid Metabolism

Abstract Herbal soups have always been a popular option for treating oxidative stress-related chronic diseases including diabetes. Various components of these soups have been studied in the hope to identify the active principles, mainly focusing on the individual phytochemicals. As we have revealed previously, the micro/nanoparticles (MNPs) formed incidentally during the boiling water extraction of herbal soups may be bioactive and functional. This study aims to elucidate the underlying mechanism of the biological functions of these MNPs. A Chinese herbal medicine soup prepared by Radix Puerariae lobatae, ginger and other three herbs, namely Ge-Gen-Qin-Lian-Tang, was employed here, as it was proven to be effective in treating type 2 diabetes clinically. The soup was separated with high-speed centrifuge (15600×g) to obtain the supernatant (solutes and nanoparticles) and sediments (MNPs), and determined for the content of three bioactive phytochemicals, e.g. puerarin, berberine and baicalin. Their hypoglycemic, hypolipidemic and antioxidant effects were determined on streptozotocin (STZ)-induced Type 2 diabetic Wistar male rats fed on high fat-high sugar diet. The animals were divided into six groups (normal control, diabetic model, whole soup, supernatant, MNPs and metformin, 8 rats each), recording weight, diet, excretion, mental status, etc. The fasting blood glucose and oral glucose tolerance test were conducted regularly. Eight weeks after the administration, the rats were sacrificed after anesthesia. Abdominal aorta blood and tissue samples of pancreas, heart, skeletal muscle, liver, kidney, spleen were collected. The glycated hemoglobin, glucose, lipid, insulin, glucagon, AMPK, SOD, puerarin, berberine, baicalin in blood plasma, insulin in pancreas, SOD in tissues, AMPK in skeletal muscle were measured. Liver tissue sections were observed with HE staining. Statistical analysis (t-test) were performed. The MNPs reduced blood glucose, ameliorated glucose tolerance, elevated insulin secretion and significantly improve glucose and lipid metabolism (P <0.05), showing stronger effects than the supernatant components. Notably, MNPs elevated the AMPK level in skeletal muscle, even more potently than the whole soup. The therapeutic effects of MNPs on the liver damage were even stronger than metformin. Meanwhile, MNPs promoted absorption of puerarin, berberine and baicalin and increase their concentration in blood (P <0.05). Therefore, the MNPs from the herbal soup exhibited more potent effects than the soluble components on ameliorating glucose and lipid metabolism and pancreatic functions of diabetic rats. The actions of these MNPs provide a new perspective for understanding the antidiabetic effects of herbal soups and serve as a vehicle for the multiple phytochemicals to synergistically possess therapeutic effects.

scholarly journals Effects of Micronutrient Supplementation on Glucose and Hepatic Lipid Metabolism in a Rat Model of Diet Induced Obesity

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1751
Author(s):  
Saroj Khatiwada ◽  
Virginie Lecomte ◽  
Michael F. Fenech ◽  
Margaret J. Morris ◽  
Christopher A. Maloney
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Glucose Tolerance ◽  
Antioxidant Capacity ◽  
Fasting Glucose ◽  
Oral Glucose ◽  
Model Assessment ◽  
Micronutrient Supplementation ◽  
Sprague Dawley ◽  
Triglyceride Accumulation

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.

Abstract P274: Fruit Extract (blueberry, Cranberry, And Promegranate) Improved Insulin Resistance In Overweight Hypertensive And Normotensive Subjects

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ludmila N Novaes ◽  
Mariele Moraes ◽  
Keyla Katayama ◽  
Carine Sangaleti ◽  
Maria Claudia Irigoyen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Repeated Measures ◽  
Hdl Cholesterol ◽  
Biochemical Tests ◽  
Fruit Extract ◽  
Hypertensive Patients ◽  
Glucose And Lipid Metabolism ◽  
Normotensive Subjects ◽  
Group B

Arterial hypertension is frequently associated to glucose and lipid metabolism abnormalities. The purpose of this study was to determine if antioxidants (fruit extract) supplementation interfere with glucose and lipid metabolism in overweight hypertensive patients. A randomized clinical trial was conducted with 30 individuals, 23 hypertensive patients (group A) and 7 normotensive controls (group B). They were randomized to take 3 capsules of different fruits extract a day (blueberry, cranberry and pomegranate) or placebo for 4 weeks. This is a crossover study, which started with placebo changed to capsules and vice versa. Blood samples were collected after 12 hours fasting for biochemical tests (glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), anthropometric assessment (weight, height, and body mass index), systolic BP, diastolic BP and heart rate were evaluated at baseline, after 4, and 8 weeks. The comparisons between groups were held with the GLM repeated measures. Twenty three hypertensive patients (age 47 years, 14 females) and 7 normotensive controls (age 40 years, 7 females) were evaluated. BMI, blood pressure, heart and lipid profile did not differ between groups. HOMAir decreased significantly in both groups. See results in table 1. Values are expressed as medians (±SD) In these preliminary results a 4-weeks supplementation of antioxidants (fruit extract) improved insulin resistance in overweight hypertensive and normotensive subjects. Financial support: FAPESP 2014/25808-3

scholarly journals Effects of Marine Drug Propylene Glycol Alginate Sodium Sulfate on Glucose and Lipid Metabolism in Mice

2021 ◽  
Vol 58 (2) ◽  
pp. 150-154
Author(s):  
Haiyue Liang ◽  
Qun Liu ◽  
Yonghong Xiu
Keyword(s):  
Lipid Metabolism ◽  
Blood Glucose ◽  
Sodium Sulfate ◽  
Glycosylated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Control Group ◽  
Distilled Water ◽  
Glucose And Lipid Metabolism ◽  
Propylene Glycol Alginate

Previous studies have shown that marine drug propylene glycol alginate sodium sulfate (PSS) plays important roles in human diseases. This study mainly explored the effects of PSS on hyperglycemia and hyperlipidemia in diabetic db/db mouse models. The db/db mice were randomly divided into 5 groups (n=12), which were model control group (distilled water), positive control group (metformin), PSS low, medium, and high dose groups (PSS25, PSS50, PSS100) and normal control group (C57/BL, distilled water). The mice in each group had free diet and water for 90 days. During the experiment, food intake was recorded every day and body weight was recorded weekly. In addition, fasting blood glucose and glycosylated hemoglobin levels were measured regularly. Finally, the contents of triglyceride (TG), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c) and total cholesterol (TC) in the serum of mice were determined. PSS can significantly reduce fasting blood glucose and glycosylated hemoglobin levels in db/db mice, and improve insulin sensitivity. Moreover, PSS can reduce the fat accumulation of db/db mice and significantly improve the blood lipid level of db/db mice. PSS can significantly improve the symptoms of glucose and lipid metabolism disorders in db/db mice.

scholarly journals Efficacy and Safety of Zhenyuan Capsule for Coronary Heart Disease with Abnormal Glucose and Lipid Metabolism: Study Protocol for a Randomized, Double-Blind, Parallel-Controlled, Multicenter Clinical Trial

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Qiao ◽  
Jingchun Zhang ◽  
Yue Liu ◽  
Zhiqi Liang ◽  
Yuhua Wang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lipid Metabolism ◽  
Blood Glucose ◽  
Glycosylated Hemoglobin ◽  
Postprandial Blood Glucose ◽  
Common Disease ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Glucose And Lipid Metabolism

Background. Coronary heart disease (CHD) and abnormal glucose and lipid metabolism are closely associated and generally coexist. The Qi and Yin deficiency syndrome is a common disease pattern encountered in traditional Chinese medicine. We designed a protocol to determine the effectiveness and safety of Zhenyuan capsules for CHD with abnormal glucose and lipid metabolism. Methods. This multicenter, randomized, double-blind, parallel-controlled trial was designed in accordance with the CONSORT. We will recruit 200 eligible male patients aged 45–75 years from three participating centers and randomly assign them to treatment and control groups (1 : 1). The primary indicators are glycosylated hemoglobin, fasting blood glucose, 2-hour postprandial blood glucose, and triglyceride levels. The secondary indicators are the Seattle Angina Questionnaire, TCM symptom indicators, ultrasonic cardiography finding, coagulation indicator, and P-selectin level. Measurements will be performed at baseline (T0), the end of the run-in period (T1), and weeks 4 (T2), 8 (T3), and 12 (T4) of the treatment period. Adverse events will be monitored during the trial. Discussion. This study aims to evaluate the efficacy and safety of Zhenyuan capsules in patients with CHD and abnormal glucose and lipid metabolism. The results will provide critical evidence of the usefulness of the Chinese herbal medicine for CHD with abnormal glucose and lipid metabolism. Trial Registration. This trial is registered with the Chinese Clinical Trials Registry, with identifier number ChiCTR-TRC-14004639, May 4, 2014.

Sign in / Sign up

Export Citation Format

Share Document