Potentiation and prolongation of the insulinotropic action of glucagon-like peptide 1 by methyl pyruvate or dimethyl ester of L-glutamic acid in a type 2 diabetes animal model.
Methyl pyruvate and the dimethyl ester of L-glutamic acid were administered intravenously, as a primed constant infusion (1.0-2.0 micromol followed by 0.5-1.0 micromol/min, both expressed per gram of body wt), in adult rats that had been injected with streptozotocin during the neonatal period. Each ester augmented plasma insulin concentration and potentiated and/or prolonged the insulinotropic action of glucagon-like peptide 1 (GLP-1) injected intravenously (5 pmol/g of body wt) at min 5 of the test. It is proposed, therefore, that suitable nonglucidic nutrients, susceptible to bypassing the site-specific defects of D-glucose transport and metabolism responsible for the preferential impairment of the B-cell secretory response to D-glucose in non-insulin-dependent diabetes, could be used to optimize the insulinotropic action of GLP-1.
Cancelas
J
J
Fundación Jiménez Diaz, Madrid, Spain.
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Malaisse
W J
WJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004357:Drug Synergism; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D001786:Blood Glucose; D005971:Glutamates; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D011773:Pyruvates; C104813:methyl pyruvate; C035873:glutamic acid dimethyl ester; D052216:Glucagon-Like Peptide 1; D005934:Glucagon