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Erschienen in: Diabetologia 1/2011

01.01.2011 | Review

Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?

verfasst von: M. A. Nauck, I. Vardarli, C. F. Deacon, J. J. Holst, J. J. Meier

Erschienen in: Diabetologia | Ausgabe 1/2011

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Abstract

The incretin hormones gastric inhibitory polypeptide and especially glucagon-like peptide (GLP) have an important physiological function in augmenting postprandial insulin secretion. Since GLP-1 may play a role in the pathophysiology and treatment of type 2 diabetes, assessment of meal-related GLP-1 secretory responses in type 2 diabetic patients vs healthy individuals is of great interest. A common view states that GLP-1 secretion in patients with type 2 diabetes is deficient and that this applies to a lesser degree in individuals with impaired glucose tolerance. Such a deficiency is the rationale for replacing endogenous incretins with GLP-1 receptor agonists or re-normalising active GLP-1 concentrations with dipeptidyl peptidase-4 inhibitors. This review summarises the literature on this topic, including a meta-analysis of published studies on GLP-1 secretion in individuals with and without diabetes after oral glucose and mixed meals. Our analysis does not support the contention of a generalised defect in nutrient-related GLP-1 secretory responses in type 2 diabetes patients. Rather, factors are identified that may determine individual incretin secretory responses and explain some of the variations in published findings of group differences in GLP-1 responses to nutrient intake.
Literatur
1.
Zurück zum Zitat Creutzfeldt W, Nauck M (1992) Gut hormones and diabetes mellitus. Diabetes/Metab Rev 8:149–177CrossRef Creutzfeldt W, Nauck M (1992) Gut hormones and diabetes mellitus. Diabetes/Metab Rev 8:149–177CrossRef
2.
Zurück zum Zitat Holst JJ, Ørskov C (2001) Incretin hormones—an update. Scand J Clin Lab Invest 234(suppl):75–85 Holst JJ, Ørskov C (2001) Incretin hormones—an update. Scand J Clin Lab Invest 234(suppl):75–85
3.
Zurück zum Zitat Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705CrossRefPubMed Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705CrossRefPubMed
4.
Zurück zum Zitat Meier JJ, Nauck MA (2004) The potential role of glucagon-like peptide 1 in diabetes. Curr Opin Investig Drugs 5:402–410PubMed Meier JJ, Nauck MA (2004) The potential role of glucagon-like peptide 1 in diabetes. Curr Opin Investig Drugs 5:402–410PubMed
5.
Zurück zum Zitat Nauck MA, Meier JJ, Creutzfeldt W (2003) Incretins and their analogues as new antidiabetic agents. Drug News Perspect 16:413–422CrossRefPubMed Nauck MA, Meier JJ, Creutzfeldt W (2003) Incretins and their analogues as new antidiabetic agents. Drug News Perspect 16:413–422CrossRefPubMed
6.
Zurück zum Zitat Nauck MA, Meier JJ (2005) Glucagon-like peptide 1 (GLP-1) and its derivatives in the treatment of diabetes. Regul Pept 124(suppl):135–148CrossRef Nauck MA, Meier JJ (2005) Glucagon-like peptide 1 (GLP-1) and its derivatives in the treatment of diabetes. Regul Pept 124(suppl):135–148CrossRef
7.
Zurück zum Zitat Deacon CF, Holst JJ (2006) Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol 38:831–844CrossRefPubMed Deacon CF, Holst JJ (2006) Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol 38:831–844CrossRefPubMed
9.
Zurück zum Zitat Holst JJ, Deacon CF (2005) Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia 48:612–615CrossRefPubMed Holst JJ, Deacon CF (2005) Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia 48:612–615CrossRefPubMed
10.
Zurück zum Zitat Toft-Nielsen MB, Madsbad S, Holst JJ (2001) Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes. J Clin Endocrinol Metab 86:3853–3860CrossRefPubMed Toft-Nielsen MB, Madsbad S, Holst JJ (2001) Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes. J Clin Endocrinol Metab 86:3853–3860CrossRefPubMed
11.
Zurück zum Zitat Lugari R, Dei Cas A, Ugolotti D et al (2002) Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non insulin-dependent) diabetes. Horm Metab Res 34:150–154CrossRefPubMed Lugari R, Dei Cas A, Ugolotti D et al (2002) Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non insulin-dependent) diabetes. Horm Metab Res 34:150–154CrossRefPubMed
12.
Zurück zum Zitat Toft-Nielsen MB, Damholt MB, Madsbad S et al (2001) Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 86:3717–3723CrossRefPubMed Toft-Nielsen MB, Damholt MB, Madsbad S et al (2001) Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 86:3717–3723CrossRefPubMed
13.
Zurück zum Zitat Nauck M, Stöckmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–54CrossRefPubMed Nauck M, Stöckmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–54CrossRefPubMed
14.
Zurück zum Zitat Knop FK, Vilsbøll T, Højberg PV et al (2007) Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 56:1951–1959CrossRefPubMed Knop FK, Vilsbøll T, Højberg PV et al (2007) Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 56:1951–1959CrossRefPubMed
15.
Zurück zum Zitat Eissele R, Göke R, Willemer S et al (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22:283–291CrossRefPubMed Eissele R, Göke R, Willemer S et al (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22:283–291CrossRefPubMed
16.
Zurück zum Zitat Kreymann B, Williams G, Ghatei MA, Bloom SR (1987) Glucagon-like peptide-1 [7-36]: a physiological incretin in man. Lancet 2:1300–1304CrossRefPubMed Kreymann B, Williams G, Ghatei MA, Bloom SR (1987) Glucagon-like peptide-1 [7-36]: a physiological incretin in man. Lancet 2:1300–1304CrossRefPubMed
17.
Zurück zum Zitat Ørskov C, Knuhtsen S, Baldissera FG, Poulsen SS, Nielsen OV, Holst JJ (1986) Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 119:1467–1475CrossRefPubMed Ørskov C, Knuhtsen S, Baldissera FG, Poulsen SS, Nielsen OV, Holst JJ (1986) Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 119:1467–1475CrossRefPubMed
18.
Zurück zum Zitat Ørskov C, Jeppesen J, Madsbad S, Holst JJ (1991) Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest 87:415–423CrossRefPubMed Ørskov C, Jeppesen J, Madsbad S, Holst JJ (1991) Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest 87:415–423CrossRefPubMed
19.
Zurück zum Zitat D’Alessio D, Thirlby R, Laschansky E, Zebroski H, Ensinck J (1993) Response of tGLP-1 to nutrients in humans. Digestion 54:377–379 D’Alessio D, Thirlby R, Laschansky E, Zebroski H, Ensinck J (1993) Response of tGLP-1 to nutrients in humans. Digestion 54:377–379
20.
Zurück zum Zitat Nauck MA, El-Ouaghlidi A, Gabrys B et al (2004) Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes. Regul Pept 122:209–217CrossRefPubMed Nauck MA, El-Ouaghlidi A, Gabrys B et al (2004) Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes. Regul Pept 122:209–217CrossRefPubMed
21.
Zurück zum Zitat Ørskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ (1994) Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide 1 in humans. Diabetes 43:535–539CrossRefPubMed Ørskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ (1994) Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide 1 in humans. Diabetes 43:535–539CrossRefPubMed
22.
Zurück zum Zitat Åhren B, Holst JJ (2001) The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50:1030–1038CrossRefPubMed Åhren B, Holst JJ (2001) The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50:1030–1038CrossRefPubMed
23.
Zurück zum Zitat Rask E, Olsson T, Soderberg S et al (2001) Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men. Diabetes Care 24:1640–1645CrossRefPubMed Rask E, Olsson T, Soderberg S et al (2001) Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men. Diabetes Care 24:1640–1645CrossRefPubMed
24.
Zurück zum Zitat Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ (2001) Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609–613CrossRefPubMed Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ (2001) Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609–613CrossRefPubMed
25.
Zurück zum Zitat Vollmer K, Holst JJ, Baller B et al (2008) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 57:678–687CrossRefPubMed Vollmer K, Holst JJ, Baller B et al (2008) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 57:678–687CrossRefPubMed
26.
Zurück zum Zitat Reimann F (2006) GLP-1. Diabetes 5(suppl 1):S 78–85 Reimann F (2006) GLP-1. Diabetes 5(suppl 1):S 78–85
27.
Zurück zum Zitat Jang HJ, Kokrashvili Z, Theodorakis MJ et al (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA 104:15069–15074CrossRefPubMed Jang HJ, Kokrashvili Z, Theodorakis MJ et al (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci USA 104:15069–15074CrossRefPubMed
28.
Zurück zum Zitat Lauffer LM, Iakoubov R, Brubaker PL (2009) GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes 58:1058–1066CrossRefPubMed Lauffer LM, Iakoubov R, Brubaker PL (2009) GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes 58:1058–1066CrossRefPubMed
29.
Zurück zum Zitat Hirasawa A, Tsumaya K, Awaji T et al (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11:90–94CrossRefPubMed Hirasawa A, Tsumaya K, Awaji T et al (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11:90–94CrossRefPubMed
30.
Zurück zum Zitat Zhao X, Cui YM, Zhou Y et al (2008) Exenatide pharmacokinetics in healthy Chinese subjects. Int J Clin Pharmacol Ther 46:459–465PubMed Zhao X, Cui YM, Zhou Y et al (2008) Exenatide pharmacokinetics in healthy Chinese subjects. Int J Clin Pharmacol Ther 46:459–465PubMed
31.
Zurück zum Zitat Gray GM (1970) Carbohydrate digestion and absorption. Gastroenterol 58:96–107 Gray GM (1970) Carbohydrate digestion and absorption. Gastroenterol 58:96–107
32.
Zurück zum Zitat Herrmann-Rinke C, Vöge A, Hess M, Göke B (1995) Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 147:25–31CrossRefPubMed Herrmann-Rinke C, Vöge A, Hess M, Göke B (1995) Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 147:25–31CrossRefPubMed
33.
Zurück zum Zitat Brubaker PL (1991) Regulation of intestinal proglucagon-derived peptide secretion by intestinal regulatory peptides. Endocrinol 128:3175–3182CrossRef Brubaker PL (1991) Regulation of intestinal proglucagon-derived peptide secretion by intestinal regulatory peptides. Endocrinol 128:3175–3182CrossRef
34.
Zurück zum Zitat Rocca AS, Brubaker PL (1999) Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140:1687–1694CrossRefPubMed Rocca AS, Brubaker PL (1999) Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140:1687–1694CrossRefPubMed
35.
Zurück zum Zitat Anini Y, Brubaker PL (2003) Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 144:3244–3250CrossRefPubMed Anini Y, Brubaker PL (2003) Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 144:3244–3250CrossRefPubMed
36.
Zurück zum Zitat Roberge JN, Brubaker PL (1993) Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. Endocrinology 133:233–240CrossRefPubMed Roberge JN, Brubaker PL (1993) Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. Endocrinology 133:233–240CrossRefPubMed
37.
Zurück zum Zitat Roberge JN, Gronau KA, Brubaker PL (1996) Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. Endocrinology 137:2383–2388CrossRefPubMed Roberge JN, Gronau KA, Brubaker PL (1996) Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. Endocrinology 137:2383–2388CrossRefPubMed
38.
Zurück zum Zitat Nauck MA, Heimesaat MM, Ørskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301–307CrossRefPubMed Nauck MA, Heimesaat MM, Ørskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301–307CrossRefPubMed
39.
Zurück zum Zitat Fieseler P, Bridenbaugh S, Nustede R et al (1995) Physiological augmentation of amino acid-induced insulin secretion by GIP and GLP-I but not by CCK-8. Am J Physiol (Endocrinol Metab) 268:E 949–955 Fieseler P, Bridenbaugh S, Nustede R et al (1995) Physiological augmentation of amino acid-induced insulin secretion by GIP and GLP-I but not by CCK-8. Am J Physiol (Endocrinol Metab) 268:E 949–955
40.
Zurück zum Zitat Balks HJ, Holst JJ, von zur Mühlen A, Brabant G (1997) Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab 82:786–790CrossRefPubMed Balks HJ, Holst JJ, von zur Mühlen A, Brabant G (1997) Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab 82:786–790CrossRefPubMed
41.
Zurück zum Zitat Beglinger S, Drewe J, Schirra J, Göke B, D’Amato M, Beglinger C (2010) Role of fat hydrolysis in regulating glucagon-like peptide-1 secretion. J Clin Endocrinol Metab 95:879–886CrossRefPubMed Beglinger S, Drewe J, Schirra J, Göke B, D’Amato M, Beglinger C (2010) Role of fat hydrolysis in regulating glucagon-like peptide-1 secretion. J Clin Endocrinol Metab 95:879–886CrossRefPubMed
42.
Zurück zum Zitat Nauck MA, Siemsglüß J, Ørskov C, Holst JJ (1996) Release of glucagon-like peptide 1 (GLP-1 [7-36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. Z Gastroenterol 34:159–166PubMed Nauck MA, Siemsglüß J, Ørskov C, Holst JJ (1996) Release of glucagon-like peptide 1 (GLP-1 [7-36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. Z Gastroenterol 34:159–166PubMed
43.
Zurück zum Zitat Hansen L, Lampert S, Mineo H, Holst JJ (2004) Neural regulation of glucagon-like peptide-1 secretion in pigs. Am J Physiol (Endocrinol Metab) 287:E 939–947 Hansen L, Lampert S, Mineo H, Holst JJ (2004) Neural regulation of glucagon-like peptide-1 secretion in pigs. Am J Physiol (Endocrinol Metab) 287:E 939–947
44.
Zurück zum Zitat Theodorakis MJ, Carlson O, Michopoulos S et al (2006) Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol (Endocrinol Metab) 290:E 550–559 Theodorakis MJ, Carlson O, Michopoulos S et al (2006) Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol (Endocrinol Metab) 290:E 550–559
45.
Zurück zum Zitat Mortensen K, Petersen LL, Orskov C (2000) Colocalization of GLP-1 and GIP in human and porcine intestine. Ann N Y Acad Sci 921:469–472CrossRefPubMed Mortensen K, Petersen LL, Orskov C (2000) Colocalization of GLP-1 and GIP in human and porcine intestine. Ann N Y Acad Sci 921:469–472CrossRefPubMed
46.
Zurück zum Zitat Nauck MA, Holst JJ, Willms B, Schmiegel W (1997) Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for type 2-diabetes. Exp Clin Endocrinol Diabetes 105:187–195CrossRefPubMed Nauck MA, Holst JJ, Willms B, Schmiegel W (1997) Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for type 2-diabetes. Exp Clin Endocrinol Diabetes 105:187–195CrossRefPubMed
47.
Zurück zum Zitat Schirra J, Katschinski M, Weidmann C et al (1996) Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 97:92–103CrossRefPubMed Schirra J, Katschinski M, Weidmann C et al (1996) Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 97:92–103CrossRefPubMed
48.
Zurück zum Zitat Miholic J, Ørskov C, Holst JJ, Kotzerke J, Meyer HJ (1991) Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. Dig Dis Sci 36:1361–1370CrossRefPubMed Miholic J, Ørskov C, Holst JJ, Kotzerke J, Meyer HJ (1991) Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. Dig Dis Sci 36:1361–1370CrossRefPubMed
49.
Zurück zum Zitat Fukase N, Takahashi H, Manaka H et al (1992) Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion. Diabetes Res Clin Pract 15:187–195CrossRefPubMed Fukase N, Takahashi H, Manaka H et al (1992) Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion. Diabetes Res Clin Pract 15:187–195CrossRefPubMed
50.
Zurück zum Zitat Patzelt C, Schiltz E (1984) Conversion of proglucagon in pancreatic alpha cells: the major endproducts are glucagon and a single peptide, the major proglucagon fragment, that contains two glucagon-like sequences. Proc Natl Acad Sci USA 81:5007–5011CrossRefPubMed Patzelt C, Schiltz E (1984) Conversion of proglucagon in pancreatic alpha cells: the major endproducts are glucagon and a single peptide, the major proglucagon fragment, that contains two glucagon-like sequences. Proc Natl Acad Sci USA 81:5007–5011CrossRefPubMed
51.
Zurück zum Zitat Migoya E, Miller J, Luo W-L et al (2010) Sitagliptin and metformin increase active GLP-1 by complementary mechanisms in treatment-naïve patients with type 2 diabetes. Diabetes 59(suppl 1):A 156 Migoya E, Miller J, Luo W-L et al (2010) Sitagliptin and metformin increase active GLP-1 by complementary mechanisms in treatment-naïve patients with type 2 diabetes. Diabetes 59(suppl 1):A 156
52.
Zurück zum Zitat Ranganath LR, Beety LM, Morgan LM, Wright JW, Howland R, Marks V (1996) Attenuated GLP-1 secretion in obesity: cause or consequence? Gut 38:916–919CrossRefPubMed Ranganath LR, Beety LM, Morgan LM, Wright JW, Howland R, Marks V (1996) Attenuated GLP-1 secretion in obesity: cause or consequence? Gut 38:916–919CrossRefPubMed
53.
Zurück zum Zitat Hansen L, Hartmann B, Mineo H, Holst JJ (2004) Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum. Regul Pept 118:11–18CrossRefPubMed Hansen L, Hartmann B, Mineo H, Holst JJ (2004) Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum. Regul Pept 118:11–18CrossRefPubMed
54.
Zurück zum Zitat Muscelli E, Mari A, Casolaro A et al (2008) Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 57:1340–1348CrossRefPubMed Muscelli E, Mari A, Casolaro A et al (2008) Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 57:1340–1348CrossRefPubMed
55.
Zurück zum Zitat Nauck MA, Kleine N, Ørskov C, Holst JJ, Willms B, Creutzfeldt W (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, Holst JJ, Willms B, Creutzfeldt W (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
56.
Zurück zum Zitat Meier JJ, Ritter PR, Jacob A et al (2010) Impact of exogenous hyperglucagonemia on postprandial concentrations of gastric inhibitory polypeptide and glucagon-like peptide-1 in humans. J Clin Endocrinol Metab 95:4061–4065CrossRefPubMed Meier JJ, Ritter PR, Jacob A et al (2010) Impact of exogenous hyperglucagonemia on postprandial concentrations of gastric inhibitory polypeptide and glucagon-like peptide-1 in humans. J Clin Endocrinol Metab 95:4061–4065CrossRefPubMed
57.
Zurück zum Zitat Ma J, Stevens JE, Cukier K et al (2009) Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetes. Diabetes Care 32:1600–1602CrossRefPubMed Ma J, Stevens JE, Cukier K et al (2009) Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetes. Diabetes Care 32:1600–1602CrossRefPubMed
58.
Zurück zum Zitat Greenfield JR, Farooqi IS, Keogh JM et al (2009) Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 89:106–113CrossRefPubMed Greenfield JR, Farooqi IS, Keogh JM et al (2009) Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 89:106–113CrossRefPubMed
59.
Zurück zum Zitat Seifarth C, Bergmann J, Holst JJ, Ritzel R, Schmiegel W, Nauck MA (1998) Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in type 2 diabetic patients. Diabet Med 15:485–491CrossRefPubMed Seifarth C, Bergmann J, Holst JJ, Ritzel R, Schmiegel W, Nauck MA (1998) Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in type 2 diabetic patients. Diabet Med 15:485–491CrossRefPubMed
60.
Zurück zum Zitat Göke B, Fuder H, Wieckhorst G et al (1995) Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve. Digestion 56:493–501CrossRefPubMed Göke B, Fuder H, Wieckhorst G et al (1995) Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve. Digestion 56:493–501CrossRefPubMed
61.
Zurück zum Zitat Lee A, Patrick P, Wishart J, Horowitz M, Morley JE (2002) The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics. Diabetes Obes Metab 4:329–335CrossRefPubMed Lee A, Patrick P, Wishart J, Horowitz M, Morley JE (2002) The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics. Diabetes Obes Metab 4:329–335CrossRefPubMed
62.
Zurück zum Zitat Yasuda N, Inoue T, Nagakura T et al (2002) Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Biochem Biophys Res Commun 298:779–784CrossRefPubMed Yasuda N, Inoue T, Nagakura T et al (2002) Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Biochem Biophys Res Commun 298:779–784CrossRefPubMed
63.
Zurück zum Zitat Burcelin R, Da Costa A, Drucker D, Thorens B (2001) Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes 50:1720–1728CrossRefPubMed Burcelin R, Da Costa A, Drucker D, Thorens B (2001) Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes 50:1720–1728CrossRefPubMed
64.
Zurück zum Zitat Kjems LL, Holst JJ, Vølund A, Madsbad S (2003) The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 52:380–386CrossRefPubMed Kjems LL, Holst JJ, Vølund A, Madsbad S (2003) The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 52:380–386CrossRefPubMed
65.
Zurück zum Zitat Kolterman OG, Kim DD, Shen L et al (2005) Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am Health Syst Pharm 62:173–181 Kolterman OG, Kim DD, Shen L et al (2005) Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am Health Syst Pharm 62:173–181
66.
Zurück zum Zitat Elbrønd B, Jakobsen G, Larsen S et al (2002) Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care 25:1398–1404CrossRefPubMed Elbrønd B, Jakobsen G, Larsen S et al (2002) Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care 25:1398–1404CrossRefPubMed
67.
Zurück zum Zitat Fonseca V, Baron M, Shao Q, Dejager S (2008) Sustained efficacy and reduced hypoglycemia during one year of treatment with vildagliptin added to insulin in patients with type 2 diabetes mellitus. Horm Metab Res 40:427–430CrossRefPubMed Fonseca V, Baron M, Shao Q, Dejager S (2008) Sustained efficacy and reduced hypoglycemia during one year of treatment with vildagliptin added to insulin in patients with type 2 diabetes mellitus. Horm Metab Res 40:427–430CrossRefPubMed
68.
Zurück zum Zitat Vilsbøll T, Krarup T, Sonne J et al (2003) Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 88:2706–2713CrossRefPubMed Vilsbøll T, Krarup T, Sonne J et al (2003) Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 88:2706–2713CrossRefPubMed
69.
Zurück zum Zitat Ryskjaer J, Deacon CF, Carr RD et al (2006) Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbA1c levels, but is not acutely affected by food intake. Eur J Endocrinol 155:485–493CrossRefPubMed Ryskjaer J, Deacon CF, Carr RD et al (2006) Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbA1c levels, but is not acutely affected by food intake. Eur J Endocrinol 155:485–493CrossRefPubMed
70.
Zurück zum Zitat Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G (2009) First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care 32:375–380CrossRefPubMed Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G (2009) First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care 32:375–380CrossRefPubMed
71.
Zurück zum Zitat Fukase N, Igarashi M, Takahashi H et al (1993) Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients. Diabet Med 10:44–49CrossRefPubMed Fukase N, Igarashi M, Takahashi H et al (1993) Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients. Diabet Med 10:44–49CrossRefPubMed
Metadaten
Titel
Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?
verfasst von
M. A. Nauck
I. Vardarli
C. F. Deacon
J. J. Holst
J. J. Meier
Publikationsdatum
01.01.2011
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 1/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-010-1896-4

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