Milrinone efficiently potentiates insulin secretion induced by orally but not intravenously administered glucose in C57BL6J mice.
To study the effect of phosphodiesterase (PDE) 3 inhibition on plasma insulin and glucose levels, the selective PDE 3 inhibitor milrinone (0.25, 1.0, and 2.5 mg/kg) was given orally to anesthetized CL57Bl/6J mice 10 min before a gastric glucose gavage (150 mg/mouse). It was found that milrinone augmented the glucose-mediated increase in plasma insulin at 1.0 and 2.5 mg/kg without, however, any improvement in glucose elimination. In contrast, when given 10 min before intravenous glucose (1 g/kg), milrinone (1 mg/kg) did not affect the insulin response to glucose. The increase in glucagon-like peptide-1 (GLP-1) levels after gastric glucose was not altered by milrinone. However, the PDE3 inhibitor augmented the insulin response to intravenous GLP-1 (2.8 nmol/kg). We therefore conclude that PDE3 inhibition by milrinone augments insulin secretion in vivo in mice after oral but not after intravenous glucose, which may be explained by enhanced response to the cAMP-dependent insulinotropic action of endogenously released GLP-1.
Degerman
Eva
E
Department of Cell and Molecular Biology, Biomedical Center, C11, 22184 Lund, Sweden.
Manganiello
Vincent
V
Holst
Jens J
JJ
Ahrén
Bo
B
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005934:Glucagon / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007441:Intubation, Gastrointestinal; D051379:Mice; D008810:Mice, Inbred C57BL; D020105:Milrinone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose; D020105:Milrinone