scholarly journals Hepatic glucose utilization in hepatic steatosis and obesity

2016 ◽  
Vol 36 (6) ◽  
Author(s):  
Georgia Keramida ◽  
James Hunter ◽  
Adrien Michael Peters
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Glucose Utilization ◽  
Graphical Analysis ◽  
Whole Body ◽  
Utilization Rate ◽  
Obese Patients ◽  
Pet Ct ◽  
Significant Difference ◽  
Hepatic Glucose

Hepatic steatosis is associated with obesity and insulin resistance. Whether hepatic glucose utilization rate (glucose phosphorylation rate; MRglu) is increased in steatosis and/or obesity is uncertain. Our aim was to determine the separate relationships of steatosis and obesity with MRglu. Sixty patients referred for routine PET/CT had dynamic PET imaging over the abdomen for 30 min post-injection of F-18-fluorodeoxyglucose (FDG), followed by Patlak–Rutland graphical analysis of the liver using abdominal aorta for arterial input signal. The plot gradient was divided by the intercept to give hepatic FDG clearance normalized to hepatic FDG distribution volume (ml/min per 100 ml) and multiplied by blood glucose to give hepatic MRglu (μmol/min per 100 ml). Hepatic steatosis was defined as CT density of ≤40 HU measured from the 60 min whole body routine PET/CT and obesity as body mass index of ≥30 kg/m2. Hepatic MRglu was higher in patients with steatosis (3.3±1.3 μmol/min per 100 ml) than those without (1.7±1.2 μmol/min per 100 ml; P<0.001) but there was no significant difference between obese (2.5±1.6 μmol/min per 100 ml) and non-obese patients (2.1±1.3 μmol/min per 100 ml). MRglu was increased in obese patients only if they had steatosis. Non-obese patients with steatosis still had increased MRglu. There was no association between MRglu and chemotherapy history. We conclude that MRglu is increased in hepatic steatosis probably through insulin resistance, hyperinsulinaemia and up-regulation of hepatic hexokinase, irrespective of obesity.

Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN-2)27 rats

1994 ◽  
Vol 267 (6) ◽  
pp. R1503-R1509 ◽  
Author(s):  
R. Vettor ◽  
I. Cusin ◽  
D. Ganten ◽  
F. Rohner-Jeanrenaud ◽  
E. Ferrannini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Adipose Tissue ◽  
Glucose Utilization ◽  
Single Gene ◽  
Whole Body ◽  
Brown Adipose ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
And Control

The link between hyperinsulinemia and hypertension is imperfectly understood. Recently, a renin gene (the mouse DBA/REN-2d gene) has been transfected into rats, leading to high blood pressure in transgene-positive animals, TGR(mREN-2)27 rats. We tested whether heterozygous hypertensive TGR(mREN-2)27 rats presented evidence of insulin resistance in comparison with the parent strain of Sprague-Dawley rats. Despite their higher blood pressure (203 +/- 8 vs. 112 +/- 6 mmHg, P < 0.001), transgenic rats had normal fasting levels of plasma glucose, insulin, free fatty acids, and triglycerides and had normal fasting rates of hepatic glucose production (by [14C]glucose infusion). During a euglycemic hyperinsulinemic clamp (3 mU/min), stimulation of whole body glucose utilization was equivalent in transgenic and control animals (12.6 +/- 0.6 vs. 10.9 +/- 1.0 mg.min-1.kg-1, respectively). Likewise, suppression of hepatic glucose output by insulin was complete in both groups. The glucose utilization index (as measured by the 2-deoxy-D-[3H]glucose technique) was similar between transgenic and control animals in several skeletal muscles (soleus, extensor digitorum longus, tibialis, diaphragm, white and red quadriceps, and white and red gastrocnemius), in white adipose tissue (periovarian and inguinal), and in brown adipose tissue. We conclude that single gene hypertension does not alter whole body and individual tissue insulin sensitivity.

Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism

2007 ◽  
Vol 292 (3) ◽  
pp. E654-E667 ◽  
Author(s):  
Dake Qi ◽  
Brian Rodrigues
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Glucose Utilization ◽  
Experimental Studies ◽  
Cardiac Metabolism ◽  
Multiple Organ ◽  
Whole Body ◽  
Metabolic Abnormalities ◽  
Organ Systems ◽  
Per Se

Insulin resistance is viewed as an insufficiency in insulin action, with glucocorticoids being recognized to play a key role in its pathogenesis. With insulin resistance, metabolism in multiple organ systems such as skeletal muscle, liver, and adipose tissue is altered. These metabolic alterations are widely believed to be important factors in the morbidity and mortality of cardiovascular disease. More importantly, clinical and experimental studies have established that metabolic abnormalities in the heart per se also play a crucial role in the development of heart failure. Following glucocorticoids, glucose utilization is compromised in the heart. This attenuated glucose metabolism is associated with altered fatty acid supply, composition, and utilization. In the heart, elevated fatty acid use has been implicated in a number of metabolic, morphological, and mechanical changes and, more recently, in “lipotoxicity”. In the present article, we review the action of glucocorticoids, their role in insulin resistance, and their influence in modulating peripheral and cardiac metabolism and heart disease.

scholarly journals Effect of Inulin-Type Carbohydrates on Insulin Resistance in Patients with Type 2 Diabetes and Obesity: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mingyue Rao ◽  
Chenlin Gao ◽  
Ling Xu ◽  
Lan Jiang ◽  
Jianhua Zhu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
The Body ◽  
Obese Patients ◽  
Significant Difference ◽  
Simple Obesity

Background. Insulin resistance (IR) is a physiological condition related to type 2 diabetes mellitus (T2DM) and obesity, which is associated with high blood insulin and glucose. Inulin-type carbohydrate (ITC) is a kind of fermentable fructan that can reduce glucose and ameliorate IR in an animal model, but the effect in clinical trials is controversial. Objective. The authors conducted a systematic literature review to evaluate the effect of ITC supplementation in ameliorating IR in T2DM and obese patients. Methods. Multiple databases were queried for studies before December 25, 2018, which involved supplementation with ITC in ameliorating IR in T2DM and obese patients. Studies that involved meta-analysis of the body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FI), HbA1c, homeostatic model assessment IR (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) of T2DM subjects were included. HOMA-IR and QUICKI were identified as the primary outcomes. A systematic review was performed to evaluate the effect of ITC on IR in obese patients. Results. The database search yielded 25 studies, which met the inclusion criteria; 11 articles were meta-analyzed, and 5 other articles on T2DM and 9 articles on simple obesity were systematically reviewed. Our results did not find ITC supplementation decrease postintervention and reduction data of BMI (P=0.08). However, it can significantly decrease postintervention and reduction data of FPG, FI, HbA1c, and HOMA-IR. Heterogeneity was eliminated by subgroup analysis according to baseline BMI. There was no significant difference in the amelioration of QUICKI between the ITC and control groups. However, the difference was statistically significant and the heterogeneity was eliminated after subgroup analysis according to intakes of ITC. 14 articles for a systematic review found that the results of blood glucose, insulin, and HbA1c were controversial. Only one of the seven studies on simple obesity concluded that ITC intervention significantly ameliorated HOMA-IR, while the other six did not. Conclusion. Supplementation of ITC can ameliorate IR in T2DM, especially in obese T2DM patients, but the effects are controversial in obese patients.

Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes

1989 ◽  
Vol 120 (3) ◽  
pp. 257-265 ◽  
Author(s):  
Ole Hother-Nielsen ◽  
Ole Schmitz ◽  
Per H. Andersen ◽  
Henning Beck-Nielsen ◽  
Oluf Pedersen
Keyword(s):  
Type Ii Diabetes ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Metformin Treatment ◽  
Obese Patients ◽  
Type Ii ◽  
Plasma Lactate ◽  
Hepatic Glucose

Abstract. Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study. Metformin 0.5 g trice daily or placebo were given for 4 weeks. At the end of each period fasting and day-time postprandial values of plasma glucose, insulin, C-peptide and lactate were determined, and in vivo insulin action was assessed using the euglycemic clamp in combination with [3-3H]glucose tracer technique. Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 ± 1.2 vs 11.4 ± 1.2 mmol/l, P< 0.01) without enhancing mean day-time plasma insulin (43 ± 4 vs 50 ± 7 mU/l, NS) or C-peptide levels (1.26 ± 0.12 vs 1.38 ± 0.18 nmol/l, NS). Fasting plasma lactate was unchanged (1.57 ± 0.16 vs 1.44 ± 0.11 mmol/l, NS), whereas mean day-time plasma lactate concentrations were slightly increased (1.78 ± 0.11 vs 1.38 ± 0.11 mmol/l, P< 0.01). The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 ± 38 vs 313 ± 33 mg · m−2 · min−1, P< 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged. Also basal glucose clearance was improved (61.0 ± 5.8 vs 50.6 ± 2.8 ml · n−2 · min−1,, P< 0.05), whereas basal hepatic glucose production was unchanged (81 ± 6 vs 77 ± 4 mg · m−2 · min−1, NS). Conclusions: 1) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion. 2) The improved glycemic control during metformin treatment was associated with an enhanced insulin-mediated glucose utilization, presumably in skeletal muscle, whereas no effect could be demonstrated on hepatic glucose production.

A randomized trial comparing fluorocholine-PET/CT with conventional imaging in prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 2-2
Author(s):  
Scott Williams ◽  
Jean-Mathieu Beauregard ◽  
Peter Roselt ◽  
Kate Moody ◽  
Richard Fisher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progressive Disease ◽  
Randomised Trial ◽  
Whole Body ◽  
Conventional Imaging ◽  
Newly Diagnosed ◽  
First Line ◽  
Pet Ct ◽  
Significant Difference ◽  
Line Imaging

2 Background: We conducted a randomised trial comparing 18Flourocholine-PET/CT (FCH) to Computed Tomography (abdomen and pelvis) plus 99mTc-Whole Body Bone Scan (Conventional Imaging [CIm]) to determine imaging performance in prostate cancer (PC). Methods: This prospective two-arm 1:1 randomised trial enrolled men with newly diagnosed or biochemically recurrent PC to first-line imaging (FLI) with either CIm or FCH. Participants without evidence of metastases proceeded to second-line imaging (SLI) using the alternative imaging strategy. The primary aim was to determine whether FCH was more effective as a FLI approach in changing management. Secondary endpoints included incremental utility of SLI and negative predictive value (NPV) based on progression-free survival (PFS). Australian New Zealand Clinical Trials Registry ACTRN12608000641392. Results: 108 men were enrolled; 44% were for staging of newly-diagnosed PC and median follow-up 43 months. Imaging impacted clinical management in 32.4% of men (95% CI=23.7-42.1%), mostly with FLI (n=30). High-impact management changes occurred in 27.8% (95% CI=16.5-41.6%) of FCH cases compared with 11.1% (95% CI=4.2-22.6%) in the CIm arm (p=0.032). The final management plan was derived using FCH in 98.1% (95% CI = 90.1-100%) of cases and 92.6% (95%CI = 82.1-97.9%) of CIm cases (p=0.242). FLI with FCH showed unequivocally N1 or M1 disease in 22.2% (95% CI = 12-35.6%), and 16.7% (95% CI = 7.9-29.3%; p= 0.531) of CIm cases. The overall NPV for stage TxN0M0 (from all imaging) was 26.3% (95% CI: 13.9 - 41.2%), with no significant difference between arms (p=0.9). For N1M0 cases, the NPV was 14.3% (95% CI: 7.1 - 35.7%). The identification of N1M0 by FCH resulted in a longer time to identification of progressive disease, with a median PFS of 32 months (95% CI=2-68months) compared with 3 months (95% CI=1-16 months) in the CIm N1M0 cohort (p=0.05). Conclusions: FCH-PET/CT identifies more high-clinical-impact lesions than CIm as first-line imaging. All imaging modalities were poor at predicting subsequent progressive disease. Isolated node-positive disease seen with FCH is associated with a longer time to - but similarly high rates of - recurrence, suggesting a lead-time bias. Clinical trial information: ACTRN12608000641392.

Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle

2005 ◽  
Vol 289 (4) ◽  
pp. E551-E561 ◽  
Author(s):  
Eugenia Carvalho ◽  
Ko Kotani ◽  
Odile D. Peroni ◽  
Barbara B. Kahn
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Transport ◽  
Fat Mass ◽  
Glucose Transporter ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Hepatic Glucose ◽  
Clamp Study

Adipose tissue plays an important role in glucose homeostasis and affects insulin sensitivity in other tissues. In obesity and type 2 diabetes, glucose transporter 4 (GLUT4) is downregulated in adipose tissue, and glucose transport is also impaired in muscle. To determine whether overexpression of GLUT4 selectively in adipose tissue could prevent insulin resistance when glucose transport is impaired in muscle, we bred muscle GLUT4 knockout (MG4KO) mice to mice overexpressing GLUT4 in adipose tissue (AG4Tg). Overexpression of GLUT4 in fat not only normalized the fasting hyperglycemia and glucose intolerance in MG4KO mice, but it reduced these parameters to below normal levels. Glucose infusion rate during a euglycemic clamp study was reduced 46% in MG4KO compared with controls and was restored to control levels in AG4Tg-MG4KO. Similarly, insulin action to suppress hepatic glucose production was impaired in MG4KO mice and was restored to control levels in AG4Tg-MG4KO. 2-Deoxyglucose uptake during the clamp was increased approximately twofold in white adipose tissue but remained reduced in skeletal muscle of AG4Tg-MG4KO mice. AG4Tg and AG4Tg-MG4KO mice have a slight increase in fat mass, a twofold elevation in serum free fatty acids, an ∼50% increase in serum leptin, and a 50% decrease in serum adiponectin. In MG4KO mice, serum resistin is increased 34% and GLUT4 overexpression in fat reverses this. Overexpression of GLUT4 in fat also reverses the enhanced clearance of an oral lipid load in MG4KO mice. Thus overexpression of GLUT4 in fat reverses whole body insulin resistance in MG4KO mice without restoring glucose transport in muscle. This effect occurs even though AG4Tg-MG4KO mice have increased fat mass and low adiponectin and is associated with normalization of elevated resistin levels.

PA.90 LIVER ENZYMES (ALT, GGT), INSULIN RESISTANCE AND HEPATIC STEATOSIS AT ULTRASONOGRAPHY IN OBESE AND SEVERELY OBESE PATIENTS

2008 ◽  
Vol 40 ◽  
pp. S107-S108
Author(s):  
G. Ricci ◽  
A. Rossi ◽  
G. Bersani ◽  
F. Pigò ◽  
G. De Fabritiis ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Liver Enzymes ◽  
Obese Patients ◽  
Severely Obese

scholarly journals Omentin-1 Levels and Non-alcoholic Fatty Liver Disease in Obese Adolescents

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Emine Turkkan ◽  
Huseyin Dag ◽  
Okan Dikker ◽  
Nevin Cetin Dag ◽  
Alper Kacar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Density Lipoprotein ◽  
Obese Patients ◽  
Alcoholic Fatty Liver ◽  
Obese Adolescents ◽  
Significant Difference ◽  
Alcoholic Fatty Liver Disease

Background: Omentin-1 is an adipocytokine secreted from visceral adipose tissue that is thought to increase insulin sensitivity. Non-alcoholic fatty liver disease (NAFLD) is a comparatively extensive problem in obese adolescents. Decreased omentin-1 levels have been reported in obese patients, but the relationship between NAFLD and omentin-1 is contradictory. Objectives: We aimed to evaluate the omentin-1 levels in the sera of obese adolescents with and without NAFLD and compare them with each other. Methods: In this study, a total of 88 adolescents (56 obese and 32 normal-weight) were enrolled. Abdominal ultrasonography (US) identified 28 obese adolescents with grade 2-3 hepatosteatosis constituting the NAFLD group and 28 without hepatosteatosis on US constituting the non-NAFLD group. The control group included 32 age- and gender-matched cases without hepatosteatosis and with normal percentile body mass index (BMI). Serum omentin-1 levels were evaluated and compared. Results: The mean age of the research group was 12.72 ± 1.91 years. Unsurprisingly, BMI, glycated hemoglobin (HbA1c), liver transaminases (AST, ALT), total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin rates were noticeably elevated in obese adolescents compared to controls (P < 0.05). However, omentin-1 and high-density lipoprotein cholesterol (HDL) levels were remarkably lower in the obese group (P < 0.05). No significant difference was found between the NAFLD and non-NAFLD groups regarding omentin-1, HbA1c, glucose, urea, creatinine, AST, C-reactive protein (CRP), total cholesterol, triglyceride, HDL, LDL, thyroid stimulating hormone, 25-hydroxyvitamin D3, HOMA-IR, and insulin. The BMI and ALT grades of the non-NAFLD group were notably lower than the NAFLD group (P < 0.05). While there was no significant difference between omentin-1 and other parameters in obese adolescents without NAFLD (P > 0.05), we found a significant difference between omentin-1 and BMI, AST, ALT, HOMA-IR, and insulin values in obese adolescents with NAFLD (P < 0.05). Conclusions: Omentin-1 levels were decreased in obese adolescents regardless of the presence of NAFLD. However, in obese patients with NAFLD, there was a significant difference between omentin-1 and several markers of obesity and insulin resistance.

scholarly journals Reduced Levels of Circulating 7α-Hydroxy-Dehydroepiandrosterone in Treated Adolescent Obese Patients

2014 ◽  
pp. 95-101
Author(s):  
L. MÁČOVÁ ◽  
M. BIČÍKOVÁ ◽  
H. ZAMRAZILOVÁ ◽  
M. HILL ◽  
H. KAZIHNITKOVÁ ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Obese Patients ◽  
Significant Difference ◽  
Before And After ◽  
Reductive Treatment ◽  
Circulating Levels

Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD 1), an enzyme that regenerates active cortisol from inert cortisone. Increased expression of 11β-HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11β-HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-oxo-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7α-OH-DHEA, 7β-OH-DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04-15.67 years, BMI greater than 90th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7α-OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854, transformed mean with 95 % confidence interval) to 1.530 nmol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1.842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1.132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7β-OH-DHEA levels was observed. In conclusions, diminished levels of 7α-OH-DHEA indicate its possible effect on activity of 11β-HSD 1. Further studies are necessary to clarify whether competitive substrates for 11β-HSD 1 such as 7α-OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity.

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