Glucagon-like peptide 1 (GLP-1): a potent gut hormone with a possible therapeutic perspective.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print Cited Medium: Print ISSN: 0940-5429 (Print) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Diabetes Mellitus, Type 1/*drug therapy ; Diabetes Mellitus, Type 2/*drug therapy ; Glucagon/*physiology ; Glucagon/*therapeutic use ; Peptide Fragments/*physiology ; Peptide Fragments/*therapeutic use ; Protein Precursors/*physiology ; Protein Precursors/*therapeutic use; Animals ; Cerebral Ventricles/drug effects ; Cerebral Ventricles/physiology ; Diabetes Mellitus, Type 1/physiopathology ; Diabetes Mellitus, Type 2/physiopathology ; Feeding Behavior/drug effects ; Feeding Behavior/physiology ; Gastric Emptying/drug effects ; Gastric Emptying/physiology ; Glucagon/metabolism ; Glucagon/pharmacology ; Glucagon-Like Peptide 1 ; Glucose/pharmacology ; Humans ; Insulin/biosynthesis ; Models, Biological ; Peptide Fragments/pharmacology ; Proinsulin/biosynthesis ; Protein Precursors/pharmacology

Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone from the lower gastrointestinal tract, partially explaining the augmented insulin response after oral compared to intravenous glucose administration in normal humans. In addition, GLP-1 also lowers glucagon concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis, and reduces food intake upon intracerebroventricular administration in animals. Therefore, GLP-1 offers some interesting perspective for the treatment of type 2, and perhaps also for type 1 diabetic patients. The other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all its activity in type-2 diabetic patients. In contrast, GLP-1 glucose-dependently stimulates insulin secretion in type-2 diabetic patients and exogenous administration of GLP-1 ([7-37] or [7-36 amide]) in doses elevating plasma concentrations to approximately three to four times physiological postprandial levels fully normalizes fasting hyperglycaemia and reduces postprandial glycaemic increments. Due to rapid proteolytic cleavage, which results in an inactive or even antagonistic fragment. GLP-1 [9-36 amide], and to rapid elimination, the half-life of GLP-1 is too short to maintain therapeutic plasma levels for sufficient periods by subcutaneous injections of the natural peptide hormone. Current research aims to characterize GLP-1 analogues with more suitable pharmacokinetic properties than the original peptide. Given the large amount of GLP-1 present in L cells, it also appears worthwhile to search for more agents that could 'mobilize' this endogenous pool of GLP-1.

166

0 (Insulin)
0 (Peptide Fragments)
0 (Protein Precursors)
89750-14-1 (Glucagon-Like Peptide 1)
9007-92-5 (Glucagon)
9035-68-1 (Proinsulin)
IY9XDZ35W2 (Glucose)

Date Created: 19981205 Date Completed: 19990205 Latest Revision: 20191102

20221213

10.1007/s005920050116

9840447