Effect of repaglinide on insulin secretion in islets from rats infused for two days with a hypertonic solution of D-glucose.
This study investigates the insulin secretory responsiveness of pancreatic islets to repaglinide in an experimental model of B-cell glucose incompetence. Rats were infused for 2 d with a 1.67 M solution of D-glucose administered at a rate close to 2.8 mL/h. This resulted in a modest rise in glycemia, a severe increase in plasma insulin concentration, an increased sensitivity of B-cells to adrenergic stress, an abnormally high insulin output from isolated islets perifused in the presence of 16.7 mM D-glucose, and a paradoxical transient increase in insulin release from the islets in response to a fall in hexose concentration. The early increment in insulin output evoked by repaglinide, in the presence of 16.7 mM D-glucose, was not lower in the islets from glucose-infused rats than in those from control rats. Moreover, when the meglitinide analog was administered concomitantly with the removal of D-glucose from the perifusion medium, the early response to repaglinide was further increased. Even after 24 min of glucose deprivation, the output of insulin by the islets from glucose-infused rats was higher in the presence of repaglinide than in its absence. These findings indicate that, in this model of B-cell dysfunction, the secretory responsiveness to repaglinide, as distinct from that to glucose, is fully preserved. Therefore, when taken into consideration together with prior observations, these findings argue in support of the use of this insulinotropic agent in the treatment of noninsulin-dependent diabetes.
Louchami
K
K
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Ladrière
L
L
Jijakli
H
H
Malaisse
W J
WJ
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology*; D005260:Female; D005950:Glucose Solution, Hypertonic / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D001549:Benzamides; D001786:Blood Glucose; D002219:Carbamates; D005950:Glucose Solution, Hypertonic; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; C072379:repaglinide; C030516:meglitinide