Insulinotropic action of methyl pyruvate: secretory, cationic, and biosynthetic aspects.
Methyl pyruvate was found to exert a dual effect on insulin release from isolated rat pancreatic islets. A positive insulinotropic action prevailed at low concentrations of D-glucose, in the 2.8 to 8.3 mM range, and at concentrations of the ester not exceeding 10.0 mM. It displayed features typical of a process of nutrient-stimulated insulin release, such as decreased K+ conductance, enhanced Ca2+ influx, and stimulation of proinsulin biosynthesis. A negative insulinotropic action of methyl pyruvate was also observed, however, at a high concentration of D-glucose (16.7 mM) and/or at a high concentration of the methyl ester (20.0 mM). It was apparently not attributable to any adverse effect of methyl pyruvate on ATP generation, but might be due to hyperpolarization of the plasma membrane. The ionic determinant(s) of the latter change was not identified. The dual effect of methyl pyruvate probably accounts for an unusual time course of the secretory response, including a dramatic and paradoxical stimulation of insulin release upon removal of the ester.
Laboratory of Experimental Medicine, Brussels Free Universtiy, Belgium.
W J
WJ
Malaisse
H
H
Jijakli
S
S
Ulusoy
L
L
Cook
L
L
Best
C
C
Viñambres
M L
ML
Villanueva-Peñacarrillo
I
I
Valverde
A
A
Sener
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008745:Methylation; D014176:Protein Biosynthesis; D019289:Pyruvic Acid / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism
D007328:Insulin; D019289:Pyruvic Acid; D005947:Glucose; D012413:Rubidium; D002118:Calcium