Stimulation of insulin secretion from pancreatic islets by the cholecystokinin-tetrapeptide analogs Trp-Pro-Asp-Phe-NH2 and Trp-Pro-Asp-Phe(4'-NO2)-NH2.
The cholecystokinin-tetrapeptide (CCK4) analogs Trp-Pro-Asp-Phe-NH2 (3) and Trp-Pro-Asp-Phe-(4'-NO2)-NH2 (4) were found to be nearly equipotent to cholecystokinin-octapeptide (CCK8) in potentiating glucose-induced insulin secretion from islets of Langerhans isolated from rat pancreas. This stimulatory action was found to be dose-dependent and, in the case of 4, to exhibit a biphasic dose-response curve; i.e., at concentrations greater than 1.0 nM, the stimulating effect of 4 is reversed. These results suggest that conformational restriction of CCK4 and/or modification of the phenylalanine residue could produce more potent analogs capable of stimulating insulin release. Such compounds could have potential therapeutic utility in the treatment of non-insulin-dependent diabetes mellitus (NIDDM).
Knittel
J J
JJ
University of Cincinnati, College of Pharmacy, OH 45267-0004.
Hafner
B
B
Patel
D G
DG
Verspohl
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats
D007328:Insulin; D010455:Peptides; D002766:Cholecystokinin