Premium
Comparison of the effect of native glucagon‐like peptide 1 and dipeptidyl peptidase IV‐resistant analogues on insulin release from rat pancreatic islets
Author(s) -
Siegel Eg,
Gritie Scharf,
Baptist Gallwitz,
Rolf Mentlein,
Corinna Morys-Wortmann,
Fölsch Ur,
Schmidt We
Publication year - 1999
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1999.00440.x
Subject(s) - dipeptidyl peptidase , dipeptidyl peptidase 4 , pancreatic islets , islet , medicine , endocrinology , glucagon like peptide 1 , insulin , glucagon , chemistry , biological activity , biochemistry , in vitro , diabetes mellitus , type 2 diabetes , biology , enzyme
Background Glucagon‐like peptide 1 (GLP‐1) stimulates insulin secretion and may improve glycaemic control in type 2 diabetes. Therapeutic use is limited by its rapid degradation, primarily by dipeptidyl peptidase IV. Materials and methods Five GLP‐1 analogues with alterations at cleavage positions were synthesized according to the Fmoc strategy and tested for metabolic stability by incubation with rat kidney membranes containing dipeptidyl peptidase IV activity. Their insulinotropic effect was compared in isolated rat pancreatic islets after 24 h maintenance in tissue culture. Ten islets per vial were incubated for 30 min; insulin was measured radioimmunologically. Each analogue was compared with GLP‐1 in the same experiment. Results All analogues were biologically active in isolated islets in the potency order da2d8 = da2 > d2d9 > da2ds8 > desamino. At 16.7 mmol L −1 glucose, GLP‐1 and GLP‐1 analogues altered as position 2, or 2 and 8 significantly ( P < 0.05) increased insulin release at 10 −9 mol L −1 . N‐terminal modification of GLP‐1 confers resistance to dipeptidyl peptidase IV degradation in rat kidney membranes in vitro . Conclusions The analogues tested are biologically active and resistant to degradation by dipeptidyl peptidase IV. Their greater metabolic stability may help to realize the potential of GLP‐1 analogues in diabetes therapy.