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Jens Otto Lunde Jørgensen – One of the best experts on this subject based on the ideXlab platform.

  • Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients.
    The Journal of clinical endocrinology and metabolism, 2019
    Co-Authors: Esben Thyssen Vestergaard, Astrid Hjelholt, Rune E. Kuhre, Niels Møller, Pierre Larraufie, Fiona M. Gribble, Frank Reimann, Niels Jessen, Jens J. Holst, Jens Otto Lunde Jørgensen
    Abstract:

    Context Glucagon-like peptpeptidea> (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fattfatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective To investigate whether lowering of serum FFA level with Acipimox affects GLP-1 secretion. Design Two randomized crossover studies were performed in human subjects. Rat intestine was perfused intra-arterially and intraluminally, and l-cells were incubated with Acipimox. Participants The participants were healthy overweight subjects and hypopituitary adult patients. Interventions The overweight participants received Acipimox 250 mg 60 minutes before an oral glucose test. The hypopituitary patients received Acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp. Results Acipimox suppressed FFA but did not affect insulin in the clinical trials. In overweight subjects, the GLP-1 increase after the oral glucose tolerance test (area under the curve) was more than doubled [4119 ± 607 pmol/L × min (Acipimox) vs 1973 ± 375 pmol/L × min (control), P = 0.004]. In hypopituitary patients, Acipimox improved insulin sensitivity (4.7 ± 0.8 mg glucose/kg/min (Acipimox) vs 3.1 ± 0.5 mg glucose/kg/min (control), P = 0.005], and GLP-1 concentrations increased ~40%. An inverse correlation between FFA and GLP-1 concentrations existed in both trials. In rat intestine, Acipimox did not affect GLP-1 secretion, and l-cells did not consistently express the putative receptor for Acipimox. Conclusions Acipimox treatment increases systemic GLP-1 levels in both obese subjects and hypopituitary patients. Our in vitro data indicate that the underlying mechanisms are indirect.

  • short term Acipimox treatment is associated with decreased cardiac parasympathetic modulation
    British Journal of Clinical Pharmacology, 2017
    Co-Authors: Esben Thyssen Vestergaard, Jens Otto Lunde Jørgensen, Niels Møller, Simon Lebech Cichosz, Jesper Fleischer
    Abstract:

    Aims The nicotinic acid analogue Acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fattfatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of Acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of Acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of Acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with Acipimox acutely affects autonomic tone. Methods We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without Acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Results Plasma glucose (4.7 vs. 4.9 mmol l–1, P = 0.02) and serum FFA (0.05 vs. 0.41 mmol l–1, P < 0.001) were significantly decreased during Acipimox treatment. Acipimox had an inhibitory effect on standard deviation of normal-to-normal intervals (41.3 vs. 45.3 ms, P = 0.01), root mean square of successive differences (23.2 vs. 11 ms, P = 0.03) and high frequency (3.79 vs 3.60 ln (ms2), P = 0.02) and these effects were reversed during clamping. Conclusions Short-term inhibition of lipolysis by Acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of Acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.

  • Short-term Acipimox treatment is associated with decreased cardiac parasympathetic modulation
    British journal of clinical pharmacology, 2017
    Co-Authors: Esben Thyssen Vestergaard, Jens Otto Lunde Jørgensen, Niels Møller, Simon Lebech Cichosz, Jesper Fleischer
    Abstract:

    Aims The nicotinic acid analogue Acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fattfatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of Acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of Acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of Acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with Acipimox acutely affects autonomic tone. Methods We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without Acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Results Plasma glucose (4.7 vs. 4.9 mmol l–1, P = 0.02) and serum FFA (0.05 vs. 0.41 mmol l–1, P 

Esben Thyssen Vestergaard – One of the best experts on this subject based on the ideXlab platform.

  • Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients.
    The Journal of clinical endocrinology and metabolism, 2019
    Co-Authors: Esben Thyssen Vestergaard, Astrid Hjelholt, Rune E. Kuhre, Niels Møller, Pierre Larraufie, Fiona M. Gribble, Frank Reimann, Niels Jessen, Jens J. Holst, Jens Otto Lunde Jørgensen
    Abstract:

    Context Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective To investigate whether lowering of serum FFA level with Acipimox affects GLP-1 secretion. Design Two randomized crossover studies were performed in human subjects. Rat intestine was perfused intra-arterially and intraluminally, and l-cells were incubated with Acipimox. Participants The participants were healthy overweight subjects and hypopituitary adult patients. Interventions The overweight participants received Acipimox 250 mg 60 minutes before an oral glucose test. The hypopituitary patients received Acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp. Results Acipimox suppressed FFA but did not affect insulin in the clinical trials. In overweight subjects, the GLP-1 increase after the oral glucose tolerance test (area under the curve) was more than doubled [4119 ± 607 pmol/L × min (Acipimox) vs 1973 ± 375 pmol/L × min (control), P = 0.004]. In hypopituitary patients, Acipimox improved insulin sensitivity (4.7 ± 0.8 mg glucose/kg/min (Acipimox) vs 3.1 ± 0.5 mg glucose/kg/min (control), P = 0.005], and GLP-1 concentrations increased ~40%. An inverse correlation between FFA and GLP-1 concentrations existed in both trials. In rat intestine, Acipimox did not affect GLP-1 secretion, and l-cells did not consistently express the putative receptor for Acipimox. Conclusions Acipimox treatment increases systemic GLP-1 levels in both obese subjects and hypopituitary patients. Our in vitro data indicate that the underlying mechanisms are indirect.

  • short term Acipimox treatment is associated with decreased cardiac parasympathetic modulation
    British Journal of Clinical Pharmacology, 2017
    Co-Authors: Esben Thyssen Vestergaard, Jens Otto Lunde Jørgensen, Niels Møller, Simon Lebech Cichosz, Jesper Fleischer
    Abstract:

    Aims The nicotinic acid analogue Acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of Acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of Acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of Acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with Acipimox acutely affects autonomic tone. Methods We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without Acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Results Plasma glucose (4.7 vs. 4.9 mmol l–1, P = 0.02) and serum FFA (0.05 vs. 0.41 mmol l–1, P < 0.001) were significantly decreased during Acipimox treatment. Acipimox had an inhibitory effect on standard deviation of normal-to-normal intervals (41.3 vs. 45.3 ms, P = 0.01), root mean square of successive differences (23.2 vs. 11 ms, P = 0.03) and high frequency (3.79 vs 3.60 ln (ms2), P = 0.02) and these effects were reversed during clamping. Conclusions Short-term inhibition of lipolysis by Acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of Acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.

  • Short-term Acipimox treatment is associated with decreased cardiac parasympathetic modulation
    British journal of clinical pharmacology, 2017
    Co-Authors: Esben Thyssen Vestergaard, Jens Otto Lunde Jørgensen, Niels Møller, Simon Lebech Cichosz, Jesper Fleischer
    Abstract:

    Aims The nicotinic acid analogue Acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of Acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of Acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of Acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with Acipimox acutely affects autonomic tone. Methods We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without Acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Results Plasma glucose (4.7 vs. 4.9 mmol l–1, P = 0.02) and serum FFA (0.05 vs. 0.41 mmol l–1, P 

A Van Tol – One of the best experts on this subject based on the ideXlab platform.

  • short term Acipimox decreases the ability of plasma from type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux a potentially adverse effect on reverse cholesterol transport
    Diabetic Medicine, 2001
    Co-Authors: Robin P F Dullaart, A Van Tol
    Abstract:

    Aims To evaluate the effect of short-term administration of the anti-lipolytic agent, Acipimox, on the ability of plasma to stimulate cellular cholesterol removal, which represents one of the first steps in the anti-atherogenic process of reverse cholcholesterol transport. Methods Eight male Type 2 diabetic patients and eight healthy subjects were studied after a 12-h fast at baseline, after 24 h of Acipimox administration, 250 mg every 4 h, and again after 1 week (recovery). Plasma lipids, apolipoprotein AI, phospholipid transfer protein (PLTP) activity, pre-beta high-density lipoproteins (HDL) in incubated plasma and efflux of radiolabelled cholesterol from Fu5AH rat hepatoma cells to plasma were measured at each time point. Results Acipimox lowered plasma triglycerides in diabetic patients (P = 0.001) and healthy subjects (P = 0.002), whereas plasma non-esterified fatty acids were decreased in diabetic patients (P = 0.001) compared with the averaged values at baseline and recovery. Acipimox decreased HDL cholesterol in healthy subjects (P = 0.007) and plasma apolipoprotein AI in both groups (P = 0.001 for diabetic patients; P = 0.008 for healthy subjects). Not only plasma PLTP activity (P = 0.001 for diabetic patients; P = 0.01 for healthy subjects), but also pre-beta HDL in incubated plasma (P = 0.001 for diabetic patients; P = 0.03 for healthy subjects) and cellular cholesterol efflux to plasma (P = 0.04 for diabetic patients; P = 0.005 for healthy subjects) were lowered by Acipimox in both groups. Conclusions Short-term Acipimox administration impairs the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux, in conjunction with alterations in HDL parameters and in PLTP activity. If the impairment of cellular cholesterol efflux to plasma is sustained with long-term treatment, this potentially adverse effect should be considered when treating diabetic dyslipidaemia with Acipimox.

  • plasma phospholipid transfer protein activity is lowered by 24 h insulin and Acipimox administration blunted response to insulin in type 2 diabetic patients
    Diabetes, 1999
    Co-Authors: S C Riemens, A Van Tol, Willem Sluiter, Robin P F Dullaart
    Abstract:

    Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to VLDL and LDL. Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins, converts HDL3 into larger and smaller particles, and is involved in pre-beta-HDL generation. We examined the effects of 24-h hyperinsulinemia (30 mU x kg(-1) x h(-1)) and 24-h Acipimox (250 mg/4 h) on plasma lipids as well as CETP and PLTP activities (measured with exogenous substrate assays) in eight healthy and eight type 2 diabetic subjects. After 24 h of insulin, plasma free fattfatty acids (FFAs), HDL cholesterol, and plasma apolipoprotein AI decreased in healthy subjects and type 2 diabetic patients (P < 0.05). Plasma triglycerides did not significantly change in either group. After 24 h of Acipimox, all parameters, including plasma triglycerides, decreased in both groups (P < 0.05). Insulin decreased plasma PLTP activity by 17.6% after 24 h in healthy subjects (P < 0.05) and 10.2% in diabetic patients (P < 0.05 vs. baseline; P < 0.05 vs. healthy subjects). Acipimox lowered PLTP activity by 10.3% in healthy subjects (P < 0.05) and 11.3% in diabetic patients (P < 0.05). When insulin was infused for 3 h after Acipimox, a further decrease was found only in healthy subjects. Plasma CETP activity decreased by 9.5% after 24 h of insulin in healthy subjects (P < 0.05), but not in diabetic patients. Acipimox did not decrease plasma CETP activity in either group. In healthy subjects, the PLTP responses with insulin and Acipimox were larger than the changes in CETP activity (P < 0.05). These findings suggest that there is a metabolic link between the regulation of plasma FFA and PLTP, but not CETP. The PLTP response to insulin is blunted in type 2 diabetes.

  • plasma phospholipid transfer protein activity is lowered by 24 h insulin and Acipimox administration blunted response to insulin in type 2 diabetic patients
    Diabetologia, 1999
    Co-Authors: R P F Dullaart, S C Riemens, W J Sluiter, A Van Tol
    Abstract:

    Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to VLDL and LDL. Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins, converts HDL 3 into larger and smaller particles, and is involved in pre‐b-HDL generation. We examined the effects of 24-h hyperinsulinemia (30 mU · kg ‐ 1 · h ‐ 1 ) and 24-h Acipimox (250 mg/4 h) on plasma lipids as well as CETP and PLTP activities (measured with exogenous substrate assays) in eight healthy and eight type 2 diabetic subjects. After 24 h of insulin, plasma free fattfatty acids (FFAs), HDL cholesterol, and plasma apolipoprotein AI decreased in h e a l t h y subjects and type 2 diabetic patients (P < 0.05). P l a s m a triglycerides did not significantly change in either group. After 24 h of Acipimox, all parameters, including plasma triglycerides, decreased in both groups (P < 0.05). Insulin decreased plasma PLTP activity by 17.6% after 24 h in healthy subjects (P < 0.05) and 10.2% in diabetic patients (P < 0.05 vs. baseline; P < 0.05 vs. h e a l t h y subjects). Acipimox lowered PLTP activity by 10.3% in healthy subjects (P < 0.05) and 11.3% in diabetic patients (P < 0.05). When insulin was infused for 3 h after Acipimox, a further decrease was found only in healthy subjects. Plasma CETP activity decreased by 9.5% after 24 h of insulin in healthy subjects (P < 0.05), but not in diabetic patients. Acipimox did not decrease plasma CETP activity in either group. In healthy subjects, the PLTP responses with insulin and Acipimox were larger than the changes in CETP activity (P < 0.05). These findings suggest that there is a metabolic link between the regulation of plasma FFA and PLT P, but not CETP. The PLTP response to insulin is blunted in type 2 diabetes. Diabetes 48:1631‐1637, 1999

Fernando Cordido – One of the best experts on this subject based on the ideXlab platform.

  • effect of acute reduction of free fatty acids by Acipimox on growth hormone releasing hormone induced gh secretion in type 1 diabetic patients
    Clinical Endocrinology, 2003
    Co-Authors: Paula Alvarez, Luisa Isidro, R Peino, Alfonso Lealcerro, Felipe F Casanueva, Carlos Dieguez, Fernando Cordido
    Abstract:

    Summary background  In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fattfatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with Acipimox, alone or in combination with GHRH, on GH secretion in DM1. methods  Six type 1 diabetic patients were studied (three women, three men), mean age of 30 ± 2·1 years, body mass index (BMI) 23·1 ± 1·5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 µg/kg intravenously (i.v.) at min 180], Acipimox (250 mg orally at min 0 and 120) and GHRH plus Acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose. result  In control subjects, the GH area under the curve (AUC; µg/l × 120 min) was for Acipimox-treated 1339 ± 292 and 1528 ± 330 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus Acipimox was 3031 ± 669, significantly greater than the response after Acipimox alone (P < 0·05) or GHRH alone (P < 0·05). In diabetic patients, the GH AUC was for Acipimox-treated 2516 ± 606 and 1821 ± 311 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus Acipimox was 7311 ± 1154, significantly greater than the response after Acipimox alone (P < 0·05) or GHRH alone (P < 0·05). The GH response after Acipimox was increased in diabetic when compared with normal (P < 0·05), with a GH AUC of 1339 ± 292 and 2515 ± 606 for normal subjects and diabetic patients, respectively. The GH response after Acipimox plus GHRH was increased in diabetic when compared with normal (P < 0·05), with a GH AUC of 3031 ± 669 and 7311 ± 1154 for normal subjects and diabetic patients, respectively. The administration of Acipimox induced a FFA reduction during the entire test. conclusions  Reduction of free fattfatty acids with Acipimox is a stimulus for GH secretion in DM1. The combined administration of GHRH plus Acipimox induces a markedly increased GH secretion in type 1 diabetic patients when compared with normal subjects. These data suggest that patients with DM1 exhibit a greater GH secretory capacity than control subjects, despite the fact that endogenous FFA levels seems to exert a greater inhibitory effect on GH secretion in these patients.

  • Effect of acute reduction of free fatty acids by Acipimox on growth hormone-releasing hormone-induced GH secretion in type 1 diabetic patients.
    Clinical endocrinology, 2003
    Co-Authors: Paula Alvarez, Luisa Isidro, R Peino, Felipe F Casanueva, Carlos Dieguez, Alfonso Leal-cerro, Fernando Cordido
    Abstract:

    Summary background  In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fattfatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with Acipimox, alone or in combination with GHRH, on GH secretion in DM1. methods  Six type 1 diabetic patients were studied (three women, three men), mean age of 30 ± 2·1 years, body mass index (BMI) 23·1 ± 1·5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 µg/kg intravenously (i.v.) at min 180], Acipimox (250 mg orally at min 0 and 120) and GHRH plus Acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose. result  In control subjects, the GH area under the curve (AUC; µg/l × 120 min) was for Acipimox-treated 1339 ± 292 and 1528 ± 330 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus Acipimox was 3031 ± 669, significantly greater than the response after Acipimox alone (P 

  • Diagnosis of growth hormone deficiency after pituitary surgery: the combined Acipimox/GH-releasing hormone test.
    Clinical endocrinology, 2003
    Co-Authors: P. Sytze Van Dam, Fernando Cordido, Felipe F Casanueva, Carlos Dieguez, Wouter R De Vries, Bernard F E Veldhuyzen, E Van Thiel, Hans P F Koppeschaar
    Abstract:

    Summary objective Reduction of plasma free fattfatty acids leads to enhanced GH response after stimulation by GH-releasing hormone (GHRH). We studied the clinical usefulness of combined administration of Acipimox and GHRH for the diagnosis of GH deficiency. design We evaluated 35 patients [mean age 53·0 years; mean body mass index (BMI) 26·7 kg/m2] after pituitary surgery. We compared GH responses after Acipimox and GHRH with the GH response during an insulin tolerance test (ITT) and, in a subgroup of 12 patients, with the GHRH/arginine test. The Acipimox/GHRH test was additionally performed in 21 control subjects (mean age 53·8 years; mean BMI 24·7 kg/m2). results In the patients, the mean (± SEM) peak GH was almost four-fold higher after Acipimox/GHRH (6·94 ± 1·07 µg/l, range 0·46–23·1; P 

Niels Møller – One of the best experts on this subject based on the ideXlab platform.

  • Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients.
    The Journal of clinical endocrinology and metabolism, 2019
    Co-Authors: Esben Thyssen Vestergaard, Astrid Hjelholt, Rune E. Kuhre, Niels Møller, Pierre Larraufie, Fiona M. Gribble, Frank Reimann, Niels Jessen, Jens J. Holst, Jens Otto Lunde Jørgensen
    Abstract:

    Context Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective To investigate whether lowering of serum FFA level with Acipimox affects GLP-1 secretion. Design Two randomized crossover studies were performed in human subjects. Rat intestine was perfused intra-arterially and intraluminally, and l-cells were incubated with Acipimox. Participants The participants were healthy overweight subjects and hypopituitary adult patients. Interventions The overweight participants received Acipimox 250 mg 60 minutes before an oral glucose test. The hypopituitary patients received Acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp. Results Acipimox suppressed FFA but did not affect insulin in the clinical trials. In overweight subjects, the GLP-1 increase after the oral glucose tolerance test (area under the curve) was more than doubled [4119 ± 607 pmol/L × min (Acipimox) vs 1973 ± 375 pmol/L × min (control), P = 0.004]. In hypopituitary patients, Acipimox improved insulin sensitivity (4.7 ± 0.8 mg glucose/kg/min (Acipimox) vs 3.1 ± 0.5 mg glucose/kg/min (control), P = 0.005], and GLP-1 concentrations increased ~40%. An inverse correlation between FFA and GLP-1 concentrations existed in both trials. In rat intestine, Acipimox did not affect GLP-1 secretion, and l-cells did not consistently express the putative receptor for Acipimox. Conclusions Acipimox treatment increases systemic GLP-1 levels in both obese subjects and hypopituitary patients. Our in vitro data indicate that the underlying mechanisms are indirect.

  • short term Acipimox treatment is associated with decreased cardiac parasympathetic modulation
    British Journal of Clinical Pharmacology, 2017
    Co-Authors: Esben Thyssen Vestergaard, Jens Otto Lunde Jørgensen, Niels Møller, Simon Lebech Cichosz, Jesper Fleischer
    Abstract:

    Aims The nicotinic acid analogue Acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of Acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of Acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of Acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with Acipimox acutely affects autonomic tone. Methods We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without Acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Results Plasma glucose (4.7 vs. 4.9 mmol l–1, P = 0.02) and serum FFA (0.05 vs. 0.41 mmol l–1, P < 0.001) were significantly decreased during Acipimox treatment. Acipimox had an inhibitory effect on standard deviation of normal-to-normal intervals (41.3 vs. 45.3 ms, P = 0.01), root mean square of successive differences (23.2 vs. 11 ms, P = 0.03) and high frequency (3.79 vs 3.60 ln (ms2), P = 0.02) and these effects were reversed during clamping. Conclusions Short-term inhibition of lipolysis by Acipimox treatment lowered circulating FFA levels, improved insulin sensitivity, and was accompanied by reduced parasympathetic tone. The effect of Acipimox on the parasympathetic modulation was reversed by hyperinsulinaemia.

  • Short-term Acipimox treatment is associated with decreased cardiac parasympathetic modulation
    British journal of clinical pharmacology, 2017
    Co-Authors: Esben Thyssen Vestergaard, Jens Otto Lunde Jørgensen, Niels Møller, Simon Lebech Cichosz, Jesper Fleischer
    Abstract:

    Aims The nicotinic acid analogue Acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of Acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of Acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of Acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with Acipimox acutely affects autonomic tone. Methods We studied heart rate variability as a measure of autonomic tone in eight hypopituitary men with and without Acipimox treatment. The standard deviation of normal-to-normal intervals, root mean square of successive differences and high frequency were measured as heart rate variability parameters. The patients were studied in the basal and insulin-stimulated state with clamped plasma glucose on two occasions in a randomized, double-blind and placebo-controlled crossover study. Results Plasma glucose (4.7 vs. 4.9 mmol l–1, P = 0.02) and serum FFA (0.05 vs. 0.41 mmol l–1, P