Stimulation of insulin release in hereditarily diabetic rats by mixed molecules formed of nateglinide and a succinic acid ester.
Hereditarily diabetic Goto-Kakizaki rats were infused for 5 min with saline, containing as required nateglinide or mixed molecules (HD154 and HD166) with both a nateglinide moiety and a succinic acid ester moiety. The dose of these agents given intravenously amounted to 5.0 nmol/g body weight in all cases. All agents provoked a comparable early increase in plasma insulin concentration. However, HD154 and HD166, but not nateglinide itself, also caused a secondary rise in plasma insulin concentration 30 min after their infusion. It is proposed that mixed molecules formed of both a hypoglycemic sulfonylurea or meglitinide analog and a succinic acid ester may be better able than the antidiabetic agents themselves to evoke a sustained stimulation of insulin release in non-insulin-dependent diabetes.
Ladriere
L
L
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Bjorkling
F
F
Malaisse
W J
WJ
D000818:Animals; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D015394:Molecular Structure; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D013386:Succinates; D000077715:Nateglinide; D010649:Phenylalanine