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Bart Staels - One of the best experts on this subject based on the ideXlab platform.
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glucose lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization
Trends in Endocrinology and Metabolism, 2014Co-Authors: Janne Prawitt, Sandrine Caron, Bart StaelsAbstract:Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling molecules via receptors, including the G protein-coupled receptor TGR5 and the nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA sequestration, which interrupts the entero-hepatic circulation of BAs, constitutes a plausible action mechanism of BA Sequestrants. An increase of intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation is the most commonly proposed mechanism, but recent studies also argue for a direct entero-hepatic action to enhance glucose utilization. We discuss here recent findings on the mechanisms of Sequestrant–mediated glucose lowering via an increase of splanchnic glucose utilization through entero-hepatic FXR signaling.
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BRIEF COMMUNICATION Open Access Plasma bile acids are not associated with energy metabolism in humans
2013Co-Authors: Gemma Brufau, Bart Staels, Matthias J Bahr, Thierry Claudel, Johann Ockenga, Klaus Hw Böker, Elizabeth J Murphy, Kris Prado, Frans Stellaard, Michael P MannsAbstract:Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA Sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA Sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA Sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18 % compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither tota
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colesevelam lowers glucose and lipid levels in type 2 diabetes the clinical evidence
Diabetes Obesity and Metabolism, 2010Co-Authors: Vivian Fonseca, Y. Handelsman, Bart StaelsAbstract:Simultaneous control of blood glucose and other risk factors such as hypertension and dyslipidaemia is essential for reducing the risk of complications associated with type 2 diabetes mellitus (T2DM). As relatively few patients with T2DM have their risk factors managed to within the limits recommended by the American Diabetes Association, American College of Endocrinology or National Cholesterol Education Program Adult Treatment Panel III guidelines, treatment that can simultaneously control more than one risk factor is of therapeutic benefit. Clinical studies have shown that bile acid Sequestrants have glucose-lowering effects in addition to their low-density lipoprotein cholesterol-lowering effects in patients with T2DM. The bile acid Sequestrant colesevelam hydrochloride is approved as an adjunct to antidiabetes therapy for improving glycaemic control in adults with T2DM. This review examines data from three phase III clinical trials that evaluated the glucose- and lipid-lowering effects of colesevelam when added to the existing antidiabetes treatment regimen of patients with T2DM.
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DOI 10.1007/s11892-009-0087-5 Bile Acid Sequestrants for Lipid and Glucose Control
2010Co-Authors: Bart Staels, Vivian Fonseca, Yehuda H, Y. HandelsmanAbstract:# The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Bile acids are generated in the liver and are traditionally recognized for their regulatory role in multiple metabolic processes including bile acid homeostasis, nutrient absorption, and cholesterol homeostasis. Recently, bile acids emerged as signaling molecules that, as ligands for the bile acid receptors farnesoid X receptor (FXR) and TGR5, activate and integrate multiple complex signaling pathways involved in lipid and glucose metabolism. Bile acid Sequestrants are pharmacologic molecules that bind to bile acids in the intestine resulting in the interruption of bile acid homeostasis and, consequently, reduction in lowdensity lipoprotein cholesterol levels in hypercholesterolemia. Bile acid Sequestrants also reduce glucose levels and improve glycemic control in persons with type 2 diabetes mellitus (T2DM). This article examines the mechanisms by which bile acid–mediated activation of FXR and TGR5 signaling pathways regulate lipid and glucose metabolism and the potential implications for bile acid Sequestrant– mediated regulation of lipid and glucose levels in T2DM. Keywords Bile acid receptor. Bile acid Sequestrant. Cholesterol. Glucose control. Lipid control. Type 2 diabetes mellitu
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Plasma bile acids are not associated with energy metabolism in humans.
Nutrition & metabolism, 2010Co-Authors: Gemma Brufau, Bart Staels, Thierry Claudel, Johann Ockenga, Klaus Hw Böker, Kris Prado, Frans Stellaard, Matthias Bahr, Elizabeth Murphy, Michael MannsAbstract:ABSTRACT: Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA Sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA Sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA Sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.
Harold E Bays - One of the best experts on this subject based on the ideXlab platform.
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colesevelam hydrochloride powder for oral suspension versus cholestyramine powder for oral suspension comparison of acceptability and tolerability
Endocrine Practice, 2011Co-Authors: Harold E Bays, Kevin C Maki, Kathy SchmitzAbstract:OBJECTIVE: To compare tolerability of colesevelam hydrochloride powder versus a cholesterol-lowering equivalent dose of generic cholestyramine powder, each mixed in water, by means of the validated Bile Acid Sequestrant Acceptability (BASA) Scale. METHODS: We conducted a randomized, single-blind, single-visit, single-site study, comparing doses of 2 different bile acid Sequestrant powders for oral suspension that produce similar cholesterol lowering: colesevelam hydrochloride (3.75 g) and generic cholestyramine (12 g), each mixed in a transparent cup with tap water. RESULTS: The study sample consisted of 42 participants-12 men and 30 women. The study subjects were non-Hispanic white (64%) or black (36%), with a mean age of 50 years and a mean body mass index of 32.2 kg/m2. The components of the BASA Scale included taste, texture, appearance, and mixability. Colesevelam hydrochloride and cholestyramine did not differ significantly when assessed by both the unweighted and the weighted global BASA Scale. Although study participants indicated that the colorless or whitish colesevelam hydrochloride powder tasted better (P<.0001), they thought that the orange-colored cholestyramine had a more appealing appearance (P<.0001). Regarding the potential for taking the drug "for the rest of your life," 71.4% of study participants rated taste as "very important," and 11.9% rated appearance as "very important. CONCLUSION: Although study participants thought that the orange-colored generic cholestyramine powder had a better appearance, they also reported that colesevelam hydrochloride for oral suspension tasted better. A minority of study participants thought appearance was "very important"; a substantial majority thought taste was "very important" for potential long-term compliance.
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the bile acid Sequestrant acceptability scale validation study
International Journal of Clinical Practice, 2010Co-Authors: Harold E Bays, K C Maki, Kathryn H SchmitzAbstract:Summary Aims: The primary objective of this study was to validate a novel Bile Acid Sequestrant Acceptability (BASA) Scale intended to assess the acceptability and/or tolerability of bile acid Sequestrant (BAS) beverage preparations. A secondary objective was to assess the utility of weightings based on subjective clinical importance for the BASA scale individual components and its composite score. Methods: This was a randomised, single-blind, single site, controlled study of oral administration of 4 g of orange-flavoured generic cholestyramine powder, 12 g of orange-flavoured generic cholestyramine powder and an orange-flavoured sweetened control drink powder, each mixed with water. Results: The study sample included 42 subjects; 26 men and 16 women. Participants were non-Hispanic white (76.2%) or black/African American (23.8%), with a mean age of 51.4 years and body mass index of 30.1 kg/m2. The components of the BASA scale were taste, texture, appearance and mixability; the possible total BASA scores ranged being 4–20; the higher the BASA scale score, the better the acceptability/tolerability. Composite BASA scale scores were significantly lower for the 4 g (mean BASA score = 10.3) and 12 g (mean BASA score = 9.4) cholestyramine compared with the control drink powder (mean BASA score = 16.7) (p < 0.001). BASA scale scores did not significantly differ between the 4 and 12 g of cholestyramine. (p = 0.215). Weighting of the components did not materially alter the results. Findings for the individual components of the BASA scale were similar to the composite values. Conclusion: The BASA scale effectively distinguished between an orange-flavoured BAS powder and a commercial orange-flavour control powder.
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colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin glucose and lipid effects
JAMA Internal Medicine, 2008Co-Authors: Harold E Bays, Ronald B Goldberg, Kenneth E Truitt, Michael R. JonesAbstract:Background Bile acid Sequestrants are a well-accepted class of cholesterol-lowering drugs. Over the last decade, small studies have indicated that these agents may also lower glucose levels in patients with type 2 diabetes mellitus (T2DM). Methods This 26-week, randomized, double-blind, placebo-controlled, parallel-group study was conducted between August 2004 and July 2006 at 54 sites in the United States and 2 in Mexico to determine the effects of colesevelam hydrochloride, a bile acid Sequestrant, in patients with inadequately controlled T2DM (hemoglobin A 1c [HbA 1c ] level, 7.5%-9.5% [baseline HbA 1c level, 8.1%]), who were receiving metformin monotherapy or metformin combined with additional oral anti–diabetes mellitus drugs. In total, 316 subjects were randomized (159 to colesevelam hydrochloride, 3.75 g/d, and 157 to matching placebo). The primary efficacy parameter was mean placebo-corrected change in HbA 1c level from baseline to week 26 (analysis was on an intent-to-treat population using a last-observation-carried-forward approach). Results Colesevelam lowered the mean HbA 1c level compared with placebo at week 26 (−0.54%; P P = .002) and combination therapy cohorts (−0.62%; P P = .01), fructosamine (−23.2 μmol/L; P P P P P P = .02) levels and (2) improved other measures of glycemic response, as well as TC/HDL-C, LDL-C/HDL-C, non–HDL-C/HDL-C, and apolipoprotein B/apolipoprotein A-I ratios ( P Conclusion Colesevelam improves glycemic and lipid parameters in patients with T2DM inadequately controlled with metformin-based therapy. Trial Registration clinicaltrials.gov Identifier:NCT00147719
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effects of colesevelam hydrochloride on low density lipoprotein cholesterol and high sensitivity c reactive protein when added to statins in patients with hypercholesterolemia
American Journal of Cardiology, 2006Co-Authors: Harold E Bays, Michael H Davidson, Michael R. Jones, Stacey L AbbyAbstract:Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with an increased risk of atherosclerotic coronary heart disease (CHD). The addition of the bile acid Sequestrants, such as colesevelam hydrochloride (HCl), to statins further reduces low-density lipoprotein (LDL) cholesterol levels. However, the effects of approved cholesterol-lowering bile acid Sequestrants on hs-CRP have not previously been reported. Three randomized, double-blind, placebo-controlled, parallel, 6-week clinical trials of similar design investigated the efficacy of adding colesevelam HCl to stable simvastatin, atorvastatin, or pravastatin treatment in 204 patients with primary hypercholesterolemia. The primary end point was the mean percent change in the LDL cholesterol levels. Secondary end points included the effects on other lipid parameters and hs-CRP levels. A pooled analysis showed that adding colesevelam HCl to statin therapy significantly lowered LDL cholesterol levels (21 mg/dl or 16% mean reduction from baseline, p = 0.0013, and 11 mg/dl or 9% mean reduction compared with placebo, p = 0.0003). Four times as many patients receiving colesevelam HCl plus a statin achieved a LDL cholesterol target of
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colesevelam hcl a non systemic lipid altering drug
Expert Opinion on Pharmacotherapy, 2003Co-Authors: Harold E Bays, Carlos A. DujovneAbstract:Colesevelam HCl (WelChol®, Sankyo Pharmaceuticals Inc.) is a bile acid Sequestrant polymer, which has been shown to significantly lower low density lipoprotein cholesterol and favourably affect high-density lipoprotein cholesterol blood levels in monotherapy and in combination with statins (HMG-CoA reductase inhibitors). Although it is similar to other bile acid Sequestrants in that it binds bile acids and is non-systemic, colesevelam HCl differs in that it has a unique polymer structure that allows for greater tolerability with less potential drug interactions than with resins. Currently, statins are the most commonly prescribed lipid-altering drugs. However, it is not uncommon that patients demonstrate true or perceived intolerances to statin therapy, that are often dose-related and may include elevations in liver or muscle enzyme blood levels, or myalgias or muscle weakness without muscle enzyme elevation. In rare circumstances, myopathy and even rhabdomyolysis can occur with statins. In addition, many...
Michael H Davidson - One of the best experts on this subject based on the ideXlab platform.
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A systematic review of bile acid Sequestrant therapy in children with familial hypercholesterolemia
Journal of clinical lipidology, 2011Co-Authors: Michael H DavidsonAbstract:Abstract Familial hypercholesterolemia, which arises as a result of a mutation in the low-density lipoprotein (LDL) receptor gene, is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C), regardless of dietary and lifestyle modifications. Pharmacological therapy is often required to adequately control the elevated LDL-C levels associated with familial hypercholesterolemia. However, children with this genetic condition present many challenges for physicians, who must weigh the benefits of lipid-lowering therapy against the risks associated with the various treatment options. Furthermore, because familial hypercholesterolemia is a chronic condition, children will likely require long-term lipid-lowering therapy. As such, the potential effect of pharmacological treatment on development is of paramount importance in this population. Bile acid Sequestrants represent a unique treatment option for children with familial hypercholesterolemia in that these agents are not systemically absorbed but rather exert their lipid-lowering effects via binding to bile acids within the gastrointestinal tract. A literature search was performed to identify clinical data related to the use of bile acid Sequestrant therapy in children (
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interrupting bile acid handling and lipid and glucose control effects of colesevelam on glucose levels
Journal of Clinical Lipidology, 2008Co-Authors: Michael H DavidsonAbstract:Abstract The digestive tract plays a key role in lipid metabolism and in cardiovascular risk through the physiology of bile acids on lipid absorption, enterohepatic recycling of bile acids, and cholesterol oxidation in synthesis of bile acids. Recent evidence associates the activation of farnesoid X receptor by bile acids with alterations in high-density lipoprotein cholesterol, triglyceride metabolism, and glucose metabolism. Bile-acid Sequestrants augment cholesterol excretion via enhanced conversion to bile acids to lower low-density lipoprotein cholesterol. Several recent studies have demonstrated a role for the bile-acid Sequestrant colesevelam hydrochloride in improving glycemic control as well as lipid profiles in subjects with type 2 diabetes. This work reviews the mechanisms of action of colesevelam hydrochloride in interrupting bile acid reabsorption and in lipid transport and glucose control.
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the use of colesevelam hydrochloride in the treatment of dyslipidemia a review
Expert Opinion on Pharmacotherapy, 2007Co-Authors: Michael H DavidsonAbstract:Bile-acid Sequestrants augment cholesterol excretion via enhanced conversion to bile acids, and act to lower low-density lipoprotein cholesterol (LDL-C), especially when combined with other cholesterol-lowering drugs. Colesevelam hydrochloride (HCL) has become the preferred drug of this class due to fewer gastrointestinal adverse effects. This article reviews the use of colesevelam in the treatment of dyslipidemia. Bile-acid Sequestrants are a class of drugs developed to lower LDL-C levels. Two of the bile-acid Sequestrants, colestyramine resin and colestipol, have been used since the 1980s, and have proven effective and safe as nonsystemic approaches to cholesterol reduction. However, tolerability and compliance issues related to palatability and gastrointestinal side effects have limited the use of these Sequestrants. Colesevelam HCL (Daiichi Sankyo, Inc., Parsippany, NJ) is a nonabsorbed lipid-lowering agent that can be used in monotherapy or in combination with an HMG-CoA reductase inhibitor to reduce...
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effects of colesevelam hydrochloride on low density lipoprotein cholesterol and high sensitivity c reactive protein when added to statins in patients with hypercholesterolemia
American Journal of Cardiology, 2006Co-Authors: Harold E Bays, Michael H Davidson, Michael R. Jones, Stacey L AbbyAbstract:Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with an increased risk of atherosclerotic coronary heart disease (CHD). The addition of the bile acid Sequestrants, such as colesevelam hydrochloride (HCl), to statins further reduces low-density lipoprotein (LDL) cholesterol levels. However, the effects of approved cholesterol-lowering bile acid Sequestrants on hs-CRP have not previously been reported. Three randomized, double-blind, placebo-controlled, parallel, 6-week clinical trials of similar design investigated the efficacy of adding colesevelam HCl to stable simvastatin, atorvastatin, or pravastatin treatment in 204 patients with primary hypercholesterolemia. The primary end point was the mean percent change in the LDL cholesterol levels. Secondary end points included the effects on other lipid parameters and hs-CRP levels. A pooled analysis showed that adding colesevelam HCl to statin therapy significantly lowered LDL cholesterol levels (21 mg/dl or 16% mean reduction from baseline, p = 0.0013, and 11 mg/dl or 9% mean reduction compared with placebo, p = 0.0003). Four times as many patients receiving colesevelam HCl plus a statin achieved a LDL cholesterol target of
Albert K Groen - One of the best experts on this subject based on the ideXlab platform.
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Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate. PLoS ONE. 2011; 6:e24564. [PubMed: 22087215
2016Co-Authors: Maxi Meissner, Albert K Groen, Hilde Herrema, Theo H. Van Dijk, Albert Gerding, Rick Havinga, Theo Boer, Dirk-jan Reijngoud, Folkert KuipersAbstract:Aims/Hypothesis: Bile acid Sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that Sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. Methods: Lean and diabetic db/db mice were treated with 2 % (wt/wt in diet) Colesevelam HCl (BAS) for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-13C]-glucose, [2-13C]-glycerol, [1-2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. Results: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001), a,300 % increased glucokinase flux (p = 0.001) and a,200 % increased total hepatic glucose production rate (p = 0.0002). BAS treatment increased glucose metabolic clearance rate by,37 % but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317) but not in liver (p = 0.189). Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030) and 3-fold in db/db mice (p = 0.002)
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beyond intestinal soap bile acids in metabolic control
Nature Reviews Endocrinology, 2014Co-Authors: Vincent W Bloks, Albert K GroenAbstract:Over the past decade, it has become apparent that bile acids are involved in a host of activities beyond their classic functions in bile formation and fat absorption. The identification of the farnesoid X receptor (FXR) as a nuclear receptor directly activated by bile acids and the discovery that bile acids are also ligands for the membrane-bound, G-protein coupled bile acid receptor 1 (also known as TGR5) have opened new avenues of research. Both FXR and TGR5 regulate various elements of glucose, lipid and energy metabolism. Consequently, a picture has emerged of bile acids acting as modulators of (postprandial) metabolism. Therefore, strategies that interfere with either bile acid metabolism or signalling cascades mediated by bile acids may represent novel therapeutic approaches for metabolic diseases. Synthetic modulators of FXR have been designed and tested, primarily in animal models. Furthermore, the use of bile acid Sequestrants to reduce plasma cholesterol levels has unexpected benefits. For example, treatment of patients with type 2 diabetes mellitus (T2DM) with Sequestrants causes substantial reductions in plasma levels of glucose and HbA1c. This Review aims to provide an overview of the molecular mechanisms by which bile acids modulate glucose and energy metabolism, particularly focusing on the glucose-lowering actions of bile acid Sequestrants in insulin resistant states and T2DM.
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Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.
PloS one, 2011Co-Authors: Maxi Meissner, Albert K Groen, Hilde Herrema, Theo H. Van Dijk, Albert Gerding, Rick Havinga, Theo Boer, Michael Müller, Dirk-jan Reijngoud, Folkert KuipersAbstract:Aims/Hypothesis: Bile acid Sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that Sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. Methods: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet) Colesevelam HCl (BAS) for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-C-13]- glucose, [2-C-13]- glycerol, [1-H-2]- galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. Results: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001), a similar to 300% increased glucokinase flux (p = 0.001) and a similar to 200% increased total hepatic glucose production rate (p = 0.0002). BAS treatment increased glucose metabolic clearance rate by similar to 37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317) but not in liver (p = 0.189). Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030) and 3-fold in db/db mice (p = 0.002). Conclusions/Interpretation: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.
Jrf Walters - One of the best experts on this subject based on the ideXlab platform.
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effects of conventional and a novel colonic release bile acid Sequestrant a3384 on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea
United European gastroenterology journal, 2017Co-Authors: Richard N Appleby, Antal Bajor, Pg Gillberg, Hans Graffner, Magnus Simren, Jrf WaltersAbstract:BackgroundPrimary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid Sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency.AimThe purpose of this study was to evaluate the pharmacological effects of conventional Sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD.MethodsPatients with seven-day 75selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g (n = 7) or placebo (n = 6). Thirteen patients were taking conventional Sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7α-hydroxy-4-cholesten-3-one (C4) measured.ResultsMedian serum FGF19 on conventional Sequestrant treatment was 28% lower than baseline values in BAD (p < 0.05). C4 on conventional se...
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Effects of conventional and a novel colonic-release bile acid Sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea:
United European gastroenterology journal, 2016Co-Authors: Richard N Appleby, Antal Bajor, Pg Gillberg, Hans Graffner, Magnus Simren, Kjell-arne Ung, Jrf WaltersAbstract:BackgroundPrimary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid Sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency.AimThe purpose of this study was to evaluate the pharmacological effects of conventional Sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD.MethodsPatients with seven-day 75selenium-homocholic acid taurine (SeHCAT) scan retention
