Departments of Medicine and Physiology (T.J.K.), University of
Alberta, Edmonton, Alberta, Canada T6G 2S2; and Laboratory of Molecular
Endocrinology (J.F.H.), Massachusetts General Hospital, Howard Hughes
Medical Institute, Harvard Medical School, Boston, Massachusetts
02114
I. Introduction
II. History of the Incretin Concept: Discoveryof Gastric InhibitoryPolypeptide
III. Discovery of GLP-1
IV. Structures of GLPs and Family of Glucagon-Related Peptides
V. Tissue Distribution of the Expression of GLPs
A. Pancreatic-cells
B. Intestinal L cells
C. Central nervous system
VI.Proglucagon Biosynthesis
A. Organization/structure of theproglucagon gene
B. Regulation of glucagon gene expression
C. Posttranslational processing of proglucagon
VII. Regulationof GLP Secretion
A. Overview
B. Intracellular signals
C.Carbohydrates
D. Fats
E. Proteins
F. Endocrine
G. Neural
H. GLP-2
VIII. Metabolism of GLPs
A. GLP-1
B. GLP-2
IX. Physiological Actions of GLPs
A. Overview
B. Pancreaticislets
C. Counterregulatory actions of GLP-1 and leptin onß-cells
D. Stomach
E. Lung
F. Brain
G. Liver,skeletal muscle, and fat
H. Pituitary, hypothalamus, and thyroid
I. Cardiovascular system
J. GLP-2
X. GLP Receptors
A.Structure
B. Signaling
C. Distribution
D. Regulation
E.GLP-2
XI. Pathophysiology of GLP-1
XII. GLP-1 as a PotentialTreatment for Diabetes Mellitus
XIII. Future Directions
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53(1):
5 - 13.
[Abstract][Full Text][PDF]
C. A. Leech and J. F. Habener Regulation of Glucagon-Like Peptide-1 Receptor and Calcium-Sensing Receptor Signaling by L-Histidine
Endocrinology,
November 1, 2003;
144(11):
4851 - 4858.
[Abstract][Full Text][PDF]
D. Burrin, X. Guan, B. Stoll, Y. M. Petersen, and P. T. Sangild Glucagon-Like Peptide 2: A Key Link between Nutrition and Intestinal Adaptation in Neonates?
J. Nutr.,
November 1, 2003;
133(11):
3712 - 3716.
[Abstract][Full Text][PDF]
J. Wang, G. Webb, Y. Cao, and D. F. Steiner Contrasting patterns of expression of transcription factors in pancreatic {alpha} and {beta} cells
PNAS,
October 28, 2003;
100(22):
12660 - 12665.
[Abstract][Full Text][PDF]
J. W. Ensinck, E. C. Laschansky, R. E. Vogel, and D. A. D'Alessio Effect of Ingested Nutrients on the Release of Thrittene into the Human Circulation
J. Clin. Endocrinol. Metab.,
October 1, 2003;
88(10):
4798 - 4804.
[Abstract][Full Text][PDF]
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]
B. Ahren, J. J. Holst, and A. Mari Characterization of GLP-1 Effects on {beta}-Cell Function After Meal Ingestion in Humans
Diabetes Care,
October 1, 2003;
26(10):
2860 - 2864.
[Abstract][Full Text][PDF]
M. Vincent, Y. Guz, M. Rozenberg, G. Webb, M. Furuta, D. Steiner, and G. Teitelman Abrogation of Protein Convertase 2 Activity Results in Delayed Islet Cell Differentiation and Maturation, Increased {alpha}-Cell Proliferation, and Islet Neogenesis
Endocrinology,
September 1, 2003;
144(9):
4061 - 4069.
[Abstract][Full Text][PDF]
N. Vrang, C. B. Phifer, M. M. Corkern, and H.-R. Berthoud Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons
Am J Physiol Regulatory Integrative Comp Physiol,
August 1, 2003;
285(2):
R470 - R478.
[Abstract][Full Text][PDF]
R. H. Lustig, P. S. Hinds, K. Ringwald-Smith, R. K. Christensen, S. C. Kaste, R. E. Schreiber, S. N. Rai, S. Y. Lensing, S. Wu, and X. Xiong Octreotide Therapy of Pediatric Hypothalamic Obesity: A Double-Blind, Placebo-Controlled Trial
J. Clin. Endocrinol. Metab.,
June 1, 2003;
88(6):
2586 - 2592.
[Abstract][Full Text][PDF]
R. Gros, X. You, L. L. Baggio, M. G. Kabir, A. M. Sadi, I. N. Mungrue, T. G. Parker, Q. Huang, D. J. Drucker, and M. Husain Cardiac Function in Mice Lacking the Glucagon-Like Peptide-1 Receptor
Endocrinology,
June 1, 2003;
144(6):
2242 - 2252.
[Abstract][Full Text][PDF]
S. L. Conarello, Z. Li, J. Ronan, R. S. Roy, L. Zhu, G. Jiang, F. Liu, J. Woods, E. Zycband, D. E. Moller, et al. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance
PNAS,
May 27, 2003;
100(11):
6825 - 6830.
[Abstract][Full Text][PDF]
X. Cao, G. Flock, C. Choi, D. M. Irwin, and D. J. Drucker Aberrant Regulation of Human Intestinal Proglucagon Gene Expression in the NCI-H716 Cell Line
Endocrinology,
May 1, 2003;
144(5):
2025 - 2033.
[Abstract][Full Text][PDF]
E. V. Polyzogopoulou, F. Kalfarentzos, A. G. Vagenakis, and T. K. Alexandrides Restoration of Euglycemia and Normal Acute Insulin Response to Glucose in Obese Subjects With Type 2 Diabetes Following Bariatric Surgery
Diabetes,
May 1, 2003;
52(5):
1098 - 1103.
[Abstract][Full Text][PDF]
F. M. Gribble, L. Williams, A. K. Simpson, and F. Reimann A Novel Glucose-Sensing Mechanism Contributing to Glucagon-Like Peptide-1 Secretion From the GLUTag Cell Line
Diabetes,
May 1, 2003;
52(5):
1147 - 1154.
[Abstract][Full Text][PDF]
N. Pamir, F. C. Lynn, A. M. J. Buchan, J. Ehses, S. A. Hinke, J. A. Pospisilik, K. Miyawaki, Y. Yamada, Y. Seino, C. H. S. McIntosh, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis
Am J Physiol Endocrinol Metab,
May 1, 2003;
284(5):
E931 - E939.
[Abstract][Full Text][PDF]
M. Nishizawa, M. C. Moore, M. Shiota, S. M. Gustavson, W. L. Snead, D. W. Neal, and A. D. Cherrington Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs
Am J Physiol Endocrinol Metab,
May 1, 2003;
284(5):
E1027 - E1036.
[Abstract][Full Text][PDF]
T. P. Vahl, B. W. Paty, B. D. Fuller, R. L. Prigeon, and D. A. D'Alessio Effects of GLP-1-(7-36)NH2, GLP-1-(7-37), and GLP-1- (9-36)NH2 on Intravenous Glucose Tolerance and Glucose-Induced Insulin Secretion in Healthy Humans
J. Clin. Endocrinol. Metab.,
April 1, 2003;
88(4):
1772 - 1779.
[Abstract][Full Text][PDF]
R. Lopez de Maturana, A. Willshaw, A. Kuntzsch, R. Rudolph, and D. Donnelly The Isolated N-terminal Domain of the Glucagon-like Peptide-1 (GLP-1) Receptor Binds Exendin Peptides with Much Higher Affinity than GLP-1
J. Biol. Chem.,
March 14, 2003;
278(12):
10195 - 10200.
[Abstract][Full Text][PDF]
S. Quddusi, T. P. Vahl, K. Hanson, R. L. Prigeon, and D. A. D'Alessio Differential Effects of Acute and Extended Infusions of Glucagon-Like Peptide-1 on First- and Second-Phase Insulin Secretion in Diabetic and Nondiabetic Humans
Diabetes Care,
March 1, 2003;
26(3):
791 - 798.
[Abstract][Full Text][PDF]
D. A. Stoffers, B. M. Desai, D. D. DeLeon, and R. A. Simmons Neonatal Exendin-4 Prevents the Development of Diabetes in the Intrauterine Growth Retarded Rat
Diabetes,
March 1, 2003;
52(3):
734 - 740.
[Abstract][Full Text][PDF]
J. A. Pospisilik, J. Martin, T. Doty, J. A. Ehses, N. Pamir, F. C. Lynn, S. Piteau, H.-U. Demuth, C. H.S. McIntosh, and R. A. Pederson Dipeptidyl Peptidase IV Inhibitor Treatment Stimulates {beta}-Cell Survival and Islet Neogenesis in Streptozotocin-Induced Diabetic Rats
Diabetes,
March 1, 2003;
52(3):
741 - 750.
[Abstract][Full Text][PDF]
K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family
Pharmacol. Rev.,
March 1, 2003;
55(1):
167 - 194.
[Abstract][Full Text][PDF]
G. Kang, J. W. Joseph, O. G. Chepurny, M. Monaco, M. B. Wheeler, J. L. Bos, F. Schwede, H.-G. Genieser, and G. G. Holz Epac-selective cAMP Analog 8-pCPT-2'-O-Me-cAMP as a Stimulus for Ca2+-induced Ca2+ Release and Exocytosis in Pancreatic beta -Cells
J. Biol. Chem.,
February 28, 2003;
278(10):
8279 - 8285.
[Abstract][Full Text][PDF]
R. W. Gelling, X. Q. Du, D. S. Dichmann, J. Romer, H. Huang, L. Cui, S. Obici, B. Tang, J. J. Holst, C. Fledelius, et al. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice
PNAS,
February 4, 2003;
100(3):
1438 - 1443.
[Abstract][Full Text][PDF]
D. D. De Leon, S. Deng, R. Madani, R. S. Ahima, D. J. Drucker, and D. A. Stoffers Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy
Diabetes,
February 1, 2003;
52(2):
365 - 371.
[Abstract][Full Text][PDF]
Y. Li, T. Hansotia, B. Yusta, F. Ris, P. A. Halban, and D. J. Drucker Glucagon-like Peptide-1 Receptor Signaling Modulates beta Cell Apoptosis
J. Biol. Chem.,
January 3, 2003;
278(1):
471 - 478.
[Abstract][Full Text][PDF]
Z. Ni, Y. Anini, X. Fang, G. Mills, P. L Brubaker, and T. Jin Transcriptional Activation of the Proglucagon Gene by Lithium and beta -Catenin in Intestinal Endocrine L Cells
J. Biol. Chem.,
January 3, 2003;
278(2):
1380 - 1387.
[Abstract][Full Text][PDF]
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