Human insulin A-chain peptide analog(s) with in vitro biological activity.
In a previous study, we showed that a synthetic human insulin 1-chain analog, named analog (3) was capable of mimicking in vitro effects of native insulin, including stimulation of cell proliferation, glucose uptake and glycogen synthesis. Here, we have synthesized three new analogs (6, 9, 12) of the human A-chain, bearing or not their N- or C-terminal residue, to determine the structural features which are responsible for their biological properties. In vitro experiments clearly demonstrated that the N-terminal part of the peptides is required for the biological activity of the molecules, suggesting its crucial role in the mechanism underlying the cellular effect. Our findings may help to better understand the mechanism of interaction between insulin and its receptor. In addition, the present data demonstrate that some mini-insulin derived from the A-chain can exert similar effects as native insulin. These small peptides may offer specific advantages over insulin in the definition of new strategies for diabetes treatment.
Le Flem
Guillaume
G
Laboratoire de Biochimie du Tissu Conjonctif, UPRES EA 3214, Faculté de Médecine, Caen Cedex, France. guillaumeleflem@hotmail.com
Pecher
Julien
J
Le Flem-Bonhomme
Valerie
V
Withdrawn
Author
A
Rochette
Jacques
J
Pujol
Jean-Pierre
JP
Bogdanowicz
Patrick
P
D017667:Adipocytes; D000704:Analysis of Variance; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000188:drug therapy; D005347:Fibroblasts; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007328:Insulin; D009842:Oligopeptides; D010455:Peptides; D006003:Glycogen; D005947:Glucose