help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Toft-Nielsen, M.-B.
Right arrow Articles by Holst, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toft-Nielsen, M.-B.
Right arrow Articles by Holst, J. J.
The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 8 3717-3723
Copyright © 2001 by The Endocrine Society

Other Original Articles

Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients

Mai-Britt Toft-Nielsen, Mette B. Damholt, Sten Madsbad, Linda M. Hilsted, Thomas E. Hughes, Birgitte K. Michelsen and Jens J. Holst

Department of Endocrinology, Hvidovre Hospital, University of Copenhagen (M.-B.T.-N., M.B.D., S.M.), DK-2650 Hvidovre, Denmark; Department of Medical Physiology, Panum Institute, University of Copenhagen (M.-B.T.-N., J.J.H.), DK-2200 Copenhagen N, Denmark; Department of Clinical Chemistry, Rigshospitalet, University of Copenhagen (L.M.H.), DK-2100 Copenhagen Ø, Denmark; Metabolic and Cardiovascular Diseases Research, Novartis Institute for Biochemical Research (T.E.H.), Summit, New Jersey 08901; and Department of Diabetes Autoimmunity, Hagedorn Research Institute (B.K.M.), DK-2820 Gentofte, Denmark

Address all correspondence and requests for reprints to: Jens Juul Holst, M.D., Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. E-mail: holst{at}mfi.ku.dk

Abstract

To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0–240 min after the start of the meal was significantly decreased in the patients (2482 ± 145 compared with 3101 ± 198 pmol/liter·240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.




This article has been cited by other articles:


Home page
 DiabetesHome page
E. Muscelli, A. Mari, A. Casolaro, S. Camastra, G. Seghieri, A. Gastaldelli, J. J. Holst, and E. Ferrannini
Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients
Diabetes, May 1, 2008; 57(5): 1340 - 1348.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Ferdaoussi, S. Abdelli, J.-Y. Yang, M. Cornu, G. Niederhauser, D. Favre, C. Widmann, R. Regazzi, B. Thorens, G. Waeber, et al.
Exendin-4 Protects {beta}-Cells From Interleukin-1{beta}-Induced Apoptosis by Interfering With the c-Jun NH2-Terminal Kinase Pathway
Diabetes, May 1, 2008; 57(5): 1205 - 1215.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
L R Ranganath
Incretins: pathophysiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
J. Clin. Pathol., April 1, 2008; 61(4): 401 - 409.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
D. Q. Pham, A. Nogid, and R. Plakogiannis
Sitagliptin: A novel agent for the management of type 2 diabetes mellitus
Am. J. Health Syst. Pharm., March 15, 2008; 65(6): 521 - 531.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Vollmer, J. J. Holst, B. Baller, M. Ellrichmann, M. A. Nauck, W. E. Schmidt, and J. J. Meier
Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance
Diabetes, March 1, 2008; 57(3): 678 - 687.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. P. Choukem and J.-F. Gautier
Comment on: Knop et al. (2007) Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes 56:1951 1959
Diabetes, January 1, 2008; 57(1): e1 - e1.
[Full Text] [PDF]

Home page
 DiabetesHome page
F. K. Knop, T. Vilsboll, S. Madsbad, T. Krarup, and J. J. Holst
Response to Comment on: Knop et al. (2007) Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes 56:1951 1959
Diabetes, January 1, 2008; 57(1): e2 - e3.
[Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
A. Karamanlis, R. Chaikomin, S. Doran, M. Bellon, F D. Bartholomeusz, J. M Wishart, K. L Jones, M. Horowitz, and C. K Rayner
Effects of protein on glycemic and incretin responses and gastric emptying after oral glucose in healthy subjects
Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1364 - 1368.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. J. Lu, Q. Yang, W. Sun, S. C. Woods, D. D'Alessio, and P. Tso
The regulation of the lymphatic secretion of glucagon-like peptide-1 (GLP-1) by intestinal absorption of fat and carbohydrate
Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G963 - G971.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. J. Holst
The Physiology of Glucagon-like Peptide 1
Physiol Rev, October 1, 2007; 87(4): 1409 - 1439.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. N. Pilichiewicz, R. Chaikomin, I. M. Brennan, J. M. Wishart, C. K. Rayner, K. L. Jones, A. J. P. M. Smout, M. Horowitz, and C. Feinle-Bisset
Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men
Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E743 - E753.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Porksen, L. B. Nielsen, A. Kaas, M. Kocova, F. Chiarelli, C. Orskov, J. J. Holst, K. B. Ploug, P. Hougaard, L. Hansen, et al.
Meal-Stimulated Glucagon Release Is Associated with Postprandial Blood Glucose Level and Does Not Interfere with Glycemic Control in Children and Adolescents with New-Onset Type 1 Diabetes
J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2910 - 2916.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. K. Knop, T. Vilsboll, P. V. Hojberg, S. Larsen, S. Madsbad, A. Volund, J. J. Holst, and T. Krarup
Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State?
Diabetes, August 1, 2007; 56(8): 1951 - 1959.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
R. E. Amori, J. Lau, and A. G. Pittas
Efficacy and Safety of Incretin Therapy in Type 2 Diabetes: Systematic Review and Meta-analysis
JAMA, July 11, 2007; 298(2): 194 - 206.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
B. Laferrere, S. Heshka, K. Wang, Y. Khan, J. McGinty, J. Teixeira, A. B. Hart, and B. Olivan
Incretin Levels and Effect Are Markedly Enhanced 1 Month After Roux-en-Y Gastric Bypass Surgery in Obese Patients With Type 2 Diabetes
Diabetes Care, July 1, 2007; 30(7): 1709 - 1716.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
C. D. Lauster, T. P. McKaveney, and S. V. Muench
Vildagliptin: A novel oral therapy for type 2 diabetes mellitus
Am. J. Health Syst. Pharm., June 15, 2007; 64(12): 1265 - 1273.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
D. Kim, L. MacConell, D. Zhuang, P. A. Kothare, M. Trautmann, M. Fineman, and K. Taylor
Effects of Once-Weekly Dosing of a Long-Acting Release Formulation of Exenatide on Glucose Control and Body Weight in Subjects With Type 2 Diabetes
Diabetes Care, June 1, 2007; 30(6): 1487 - 1493.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
G. Xu, H. Kaneto, D. R. Laybutt, V. F. Duvivier-Kali, N. Trivedi, K. Suzuma, G. L. King, G. C. Weir, and S. Bonner-Weir
Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia: Possible Contribution to Impaired Incretin Effects in Diabetes
Diabetes, June 1, 2007; 56(6): 1551 - 1558.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Y.-S. Lee, S. Shin, T. Shigihara, E. Hahm, M.-J. Liu, J. Han, J.-W. Yoon, and H.-S. Jun
Glucagon-Like Peptide-1 Gene Therapy in Obese Diabetic Mice Results in Long-Term Cure of Diabetes by Improving Insulin Sensitivity and Reducing Hepatic Gluconeogenesis
Diabetes, June 1, 2007; 56(6): 1671 - 1679.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
B. E. Dunning and J. E. Gerich
The Role of {alpha}-Cell Dysregulation in Fasting and Postprandial Hyperglycemia in Type 2 Diabetes and Therapeutic Implications
Endocr. Rev., May 1, 2007; 28(3): 253 - 283.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
Y.-L. He, Y. Wang, J. M. Bullock, C. F. Deacon, J. J. Holst, B. E. Dunning, M. Ligueros-Saylan, and J. E. Foley
Pharmacodynamics of Vildagliptin in Patients With Type 2 Diabetes During OGTT
J. Clin. Pharmacol., May 1, 2007; 47(5): 633 - 641.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
B. L. Wajchenberg
{beta}-Cell Failure in Diabetes and Preservation by Clinical Treatment
Endocr. Rev., April 1, 2007; 28(2): 187 - 218.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
B. Ahren
Insulin Secretion and Insulin Sensitivity in Relation to Fasting Glucose in Healthy Subjects
Diabetes Care, March 1, 2007; 30(3): 644 - 648.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. Iakoubov, A. Izzo, A. Yeung, C. I. Whiteside, and P. L. Brubaker
Protein Kinase C{zeta} Is Required for Oleic Acid-Induced Secretion of Glucagon-Like Peptide-1 by Intestinal Endocrine L Cells
Endocrinology, March 1, 2007; 148(3): 1089 - 1098.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
R K. Campbell
Rationale for Dipeptidyl Peptidase 4 Inhibitors: A New Class of Oral Agents for the Treatment of Type 2 Diabetes Mellitus
Ann. Pharmacother., January 1, 2007; 41(1): 51 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
E. Muscelli, A. Mari, A. Natali, B. D. Astiarraga, S. Camastra, S. Frascerra, J. J. Holst, and E. Ferrannini
Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1144 - E1150.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
G. E. Lim and P. L. Brubaker
Glucagon-Like Peptide 1 Secretion by the L-Cell: The View From Within
Diabetes, December 1, 2006; 55(Supplement_2): S70 - S77.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes Spectr.Home page
S. R. Gambert and S. Pinkstaff
Emerging Epidemic: Diabetes in Older Adults: Demography, Economic Impact, and Pathophysiology
Diabetes Spectr, October 1, 2006; 19(4): 221 - 228.
[Abstract] [Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
D. F. Kruger, C. L. Martin, and C. E. Sadler
New insights into glucose regulation.
The Diabetes Educator, March 1, 2006; 32(2): 221 - 228.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. J. Theodorakis, O. Carlson, S. Michopoulos, M. E. Doyle, M. Juhaszova, K. Petraki, and J. M. Egan
Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP
Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E550 - E559.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. T. Schmidt, E. Naslund, P. Gryback, H. Jacobsson, J. J. Holst, L. Hilsted, and P. M. Hellstrom
A Role for Pancreatic Polypeptide in the Regulation of Gastric Emptying and Short-Term Metabolic Control
J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5241 - 5246.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. Chaikomin, S. Doran, K. L. Jones, C. Feinle-Bisset, D. O'Donovan, C. K. Rayner, and M. Horowitz
Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects
Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E504 - E507.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. H. Schou, K. Pilgaard, T. Vilsboll, C. B. Jensen, C. F. Deacon, J. J. Holst, A. Volund, S. Madsbad, and A. A. Vaag
Normal Secretion and Action of the Gut Incretin Hormones Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide in Young Men with Low Birth Weight
J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4912 - 4919.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. A. Nauck, B. Baller, and J. J. Meier
Gastric Inhibitory Polypeptide and Glucagon-Like Peptide-1 in the Pathogenesis of Type 2 Diabetes
Diabetes, December 1, 2004; 53(suppl_3): S190 - S196.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. J. Holst and C. Orskov
The Incretin Approach for Diabetes Treatment: Modulation of Islet Hormone Release by GLP-1 Agonism
Diabetes, December 1, 2004; 53(suppl_3): S197 - S204.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
Z. T. Bloomgarden
Gut-Derived Incretin Hormones and New Therapeutic Approaches
Diabetes Care, October 1, 2004; 27(10): 2554 - 2559.
[Full Text] [PDF]

Home page
 DiabetesHome page
K. B. Degn, B. Brock, C. B. Juhl, C. B. Djurhuus, J. Grubert, D. Kim, J. Han, K. Taylor, M. Fineman, and O. Schmitz
Effect of Intravenous Infusion of Exenatide (Synthetic Exendin-4) on Glucose-Dependent Insulin Secretion and Counterregulation During Hypoglycemia
Diabetes, September 1, 2004; 53(9): 2397 - 2403.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. J. Holst and J. Gromada
Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans
Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E199 - E206.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes Spectr.Home page
S. L. Aronoff, K. Berkowitz, B. Shreiner, and L. Want
Glucose Metabolism and Regulation: Beyond Insulin and Glucagon
Diabetes Spectr, July 1, 2004; 17(3): 183 - 190.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
D. A. D'Alessio and T. P. Vahl
Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes
Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E882 - E890.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
G. S. Meneilly, N. Greig, H. Tildesley, J. F. Habener, J. M. Egan, and D. Elahi
Effects of 3 Months of Continuous Subcutaneous Administration of Glucagon-Like Peptide 1 in Elderly Patients With Type 2 Diabetes
Diabetes Care, October 1, 2003; 26(10): 2835 - 2841.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Vilsboll, T. Krarup, J. Sonne, S. Madsbad, A. Volund, A. G. Juul, and J. J. Holst
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., June 1, 2003; 88(6): 2706 - 2713.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society