Skip to main content
Top
Published in: Diabetologia 3/2006

01-03-2006 | Article

Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

Authors: J. J. Meier, A. Gethmann, O. Götze, B. Gallwitz, J. J. Holst, W. E. Schmidt, M. A. Nauck

Published in: Diabetologia | Issue 3/2006

Login to get access

Abstract

Aims/hypothesis

Diabetic dyslipidaemia contributes to the excess morbidity and mortality in patients with type 2 diabetes. Exogenous glucagon-like peptide 1 (GLP-1) lowers postprandial glycaemia predominantly by slowing gastric emptying. Therefore, the effects of GLP-1 on postprandial lipid levels and gastric emptying were assessed.

Methods

14 healthy male volunteers were studied with an i.v. infusion of GLP-1 (1.2 pmol kg−1 min−1) or placebo over 390 min in the fasting state. A solid test meal was served and gastric emptying was determined using a 13C-labelled sodium octanoate breath test. Venous blood was drawn frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1, triglycerides and NEFA.

Results

GLP-1 administration lowered fasting and postprandial glycaemia (p<0.0001). Gastric emptying was delayed by GLP-1 compared with placebo (p<0.0001). During GLP-1 administration, insulin secretory responses were higher in the fasting state but lower after meal ingestion. After meal ingestion, triglyceride plasma levels increased by 0.33±0.14 mmol/l in the placebo experiments (p<0.0001). In contrast, the postprandial increase in triglyceride levels was completely abolished by GLP-1 (change in triglycerides, −0.023±0.045 mmol/l; p<0.05). During GLP-1 infusion, plasma concentrations of NEFA were suppressed by 39% in the fasting state (p<0.01) and by 31±5% after meal ingestion (p<0.01).

Conclusions/interpretation

GLP-1 improves postprandial lipidaemia, presumably as a result of delayed gastric emptying and insulin-mediated inhibition of lipolysis. Thus, by lowering both glucose and lipid concentrations, GLP-1 administration may reduce the cardiovascular risk in patients with type 2 diabetes.
Literature
1.
go back to reference Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749CrossRefPubMed Taskinen MR (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46:733–749CrossRefPubMed
2.
go back to reference Stampfer MJ, Krauss RM, Ma J et al (1996) A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 276:882–888CrossRefPubMed Stampfer MJ, Krauss RM, Ma J et al (1996) A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 276:882–888CrossRefPubMed
3.
go back to reference Patsch JR, Miesenbock G, Hopferwieser T et al (1992) Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb 12:1336–1345PubMed Patsch JR, Miesenbock G, Hopferwieser T et al (1992) Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb 12:1336–1345PubMed
4.
go back to reference Temelkova-Kurktschiev T, Hanefeld M (2004) The lipid triad in type 2 diabetes—prevalence and relevance of hypertriglyceridaemia/low high-density lipoprotein syndrome in type 2 diabetes. Exp Clin Endocrinol Diabetes 112:757–759 Temelkova-Kurktschiev T, Hanefeld M (2004) The lipid triad in type 2 diabetes—prevalence and relevance of hypertriglyceridaemia/low high-density lipoprotein syndrome in type 2 diabetes. Exp Clin Endocrinol Diabetes 112:757–759
5.
go back to reference Lundman P, Eriksson MJ, Stuhlinger M et al (2001) Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine. J Am Coll Cardiol 38:111–116CrossRefPubMed Lundman P, Eriksson MJ, Stuhlinger M et al (2001) Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine. J Am Coll Cardiol 38:111–116CrossRefPubMed
6.
go back to reference Hennig B, Toborek M, McClain CJ (2001) High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis. J Am Coll Nutr 20:97–105PubMed Hennig B, Toborek M, McClain CJ (2001) High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis. J Am Coll Nutr 20:97–105PubMed
7.
go back to reference Drucker DJ (2003) Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 26:2929–2940PubMedCrossRef Drucker DJ (2003) Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 26:2929–2940PubMedCrossRef
8.
go back to reference Meier JJ, Nauck MA (2005) Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes Metab Res Rev 21:91–117CrossRefPubMed Meier JJ, Nauck MA (2005) Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes Metab Res Rev 21:91–117CrossRefPubMed
9.
go back to reference Gutniak MK, Holst JJ, Ørskov C, Åhren B, Efendic S (1992) Antidiabetogenic effect of glucagon-like peptide-1 (7–36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med 326:1316–1322PubMedCrossRef Gutniak MK, Holst JJ, Ørskov C, Åhren B, Efendic S (1992) Antidiabetogenic effect of glucagon-like peptide-1 (7–36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med 326:1316–1322PubMedCrossRef
10.
go back to reference Wettergren A, Schjoldager B, Mortensen PE et al (1993) Truncated GLP-1 (proglucagon 78–107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 38:665–673CrossRefPubMed Wettergren A, Schjoldager B, Mortensen PE et al (1993) Truncated GLP-1 (proglucagon 78–107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 38:665–673CrossRefPubMed
11.
go back to reference Meier JJ, Gallwitz B, Salmen S et al (2003) Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 88:2719–2725CrossRefPubMed Meier JJ, Gallwitz B, Salmen S et al (2003) Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 88:2719–2725CrossRefPubMed
12.
go back to reference Meier JJ, Kemmeries G, Holst JJ, Nauck MA (2005) Erythromycin antagonises the deceleration of gastric emptying by glucagon-like peptide 1 (GLP-1) and unmasks its insulinotropic effect in healthy subjects. Diabetes 54:2212–2218PubMedCrossRef Meier JJ, Kemmeries G, Holst JJ, Nauck MA (2005) Erythromycin antagonises the deceleration of gastric emptying by glucagon-like peptide 1 (GLP-1) and unmasks its insulinotropic effect in healthy subjects. Diabetes 54:2212–2218PubMedCrossRef
13.
go back to reference Ghoos YF, Maes BD, Geypens BJ et al (1993) Measurement of gastric emptying rate of solid meals by means of a carbon-labeled octanoic acid breath test. Gastroenterology 104:1640–1647PubMed Ghoos YF, Maes BD, Geypens BJ et al (1993) Measurement of gastric emptying rate of solid meals by means of a carbon-labeled octanoic acid breath test. Gastroenterology 104:1640–1647PubMed
14.
go back to reference Meier JJ, Hücking K, Holst JJ et al (2001) Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes 50:2497–2504PubMedCrossRef Meier JJ, Hücking K, Holst JJ et al (2001) Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes 50:2497–2504PubMedCrossRef
16.
go back to reference Nauck MA, Kleine N, Ørskov C et al (1993) Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36:741–744CrossRefPubMed Nauck MA, Kleine N, Ørskov C et al (1993) Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36:741–744CrossRefPubMed
17.
go back to reference Boden G, Jadali F (1991) Effects of lipid on basal carbohydrate metabolism in normal men. Diabetes 40:686–692PubMedCrossRef Boden G, Jadali F (1991) Effects of lipid on basal carbohydrate metabolism in normal men. Diabetes 40:686–692PubMedCrossRef
18.
go back to reference Zander M, Madsbad S, Madsen JL, Holst JJ (2002) Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 359:824–830CrossRefPubMed Zander M, Madsbad S, Madsen JL, Holst JJ (2002) Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 359:824–830CrossRefPubMed
19.
go back to reference Willms B, Werner J, Holst JJ et al (1996) Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7–36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 81:327–332CrossRefPubMed Willms B, Werner J, Holst JJ et al (1996) Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7–36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 81:327–332CrossRefPubMed
20.
go back to reference Schirra J, Nicolaus M, Roggel R et al. (2005) Endogenous GLP-1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut 28. E-pub ahead of print Schirra J, Nicolaus M, Roggel R et al. (2005) Endogenous GLP-1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut 28. E-pub ahead of print
21.
go back to reference Wojdemann M, Wettergren A, Sternby B et al (1998) Inhibition of human gastric lipase secretion by glucagon-like peptide-1. Dig Dis Sci 43:799–805CrossRefPubMed Wojdemann M, Wettergren A, Sternby B et al (1998) Inhibition of human gastric lipase secretion by glucagon-like peptide-1. Dig Dis Sci 43:799–805CrossRefPubMed
22.
go back to reference Qin X, Shen H, Liu M et al (2005) GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats. Am J Physiol Gastrointest Liver Physiol 288:G943–G949CrossRefPubMed Qin X, Shen H, Liu M et al (2005) GLP-1 reduces intestinal lymph flow, triglyceride absorption, and apolipoprotein production in rats. Am J Physiol Gastrointest Liver Physiol 288:G943–G949CrossRefPubMed
23.
go back to reference Mahler R, Stafford WS, Tarrant ME, Ashmore J (1964) The effect of insulin on lipolysis. Diabetes 13:297–302PubMed Mahler R, Stafford WS, Tarrant ME, Ashmore J (1964) The effect of insulin on lipolysis. Diabetes 13:297–302PubMed
24.
go back to reference Samols E, Stagner JI, Ewart RB, Marks V (1988) The order of islet microvascular cellular perfusion is B–A–D in the perfused rat pancreas. J Clin Invest 82:350–353PubMed Samols E, Stagner JI, Ewart RB, Marks V (1988) The order of islet microvascular cellular perfusion is B–A–D in the perfused rat pancreas. J Clin Invest 82:350–353PubMed
25.
go back to reference Weir GC, Bonner-Weir S (1990) Islets of Langerhans: the puzzle of intraislet interactions and their relevance to diabetes. J Clin Invest 85:983–987.PubMedCrossRef Weir GC, Bonner-Weir S (1990) Islets of Langerhans: the puzzle of intraislet interactions and their relevance to diabetes. J Clin Invest 85:983–987.PubMedCrossRef
26.
go back to reference Franklin I, Gromada J, Gjinovci A, Theander S, Wollheim CB (2005) Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release. Diabetes 54:1808–1815PubMedCrossRef Franklin I, Gromada J, Gjinovci A, Theander S, Wollheim CB (2005) Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release. Diabetes 54:1808–1815PubMedCrossRef
27.
go back to reference Braden B, Adams S, Duan LP et al (1995) The [13C]acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals. Gastroenterology 108:1048–1055CrossRefPubMed Braden B, Adams S, Duan LP et al (1995) The [13C]acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals. Gastroenterology 108:1048–1055CrossRefPubMed
28.
go back to reference Nauck MA, Meier JJ (2005) Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul Pept 128:135–148CrossRefPubMed Nauck MA, Meier JJ (2005) Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul Pept 128:135–148CrossRefPubMed
29.
go back to reference Toft-Nielsen M-B, Madsbad S, Holst JJ (1999) Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 22:1137–1143PubMedCrossRef Toft-Nielsen M-B, Madsbad S, Holst JJ (1999) Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 22:1137–1143PubMedCrossRef
30.
go back to reference Fineman MS, Bicsak TA, Shen LZ et al (2003) Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 26:2370–2377PubMedCrossRef Fineman MS, Bicsak TA, Shen LZ et al (2003) Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 26:2370–2377PubMedCrossRef
31.
go back to reference Defronzo RA, Ratner RE, Han J et al (2005) Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28:1092–1100PubMedCrossRef Defronzo RA, Ratner RE, Han J et al (2005) Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28:1092–1100PubMedCrossRef
32.
go back to reference Buse JB, Henry RR, Han J et al (2004) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27:2628–2635PubMedCrossRef Buse JB, Henry RR, Han J et al (2004) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27:2628–2635PubMedCrossRef
33.
go back to reference Schirra J, Houk P, Wank U et al (2000) Effects of glucagon-like peptide-1 (7–36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut 56:622–631CrossRef Schirra J, Houk P, Wank U et al (2000) Effects of glucagon-like peptide-1 (7–36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut 56:622–631CrossRef
Metadata
Title
Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans
Authors
J. J. Meier
A. Gethmann
O. Götze
B. Gallwitz
J. J. Holst
W. E. Schmidt
M. A. Nauck
Publication date
01-03-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 3/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-0126-y

Other articles of this Issue 3/2006

Diabetologia 3/2006 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.