Inhibitory effect of D-myo-inositol-1,2,6-trisphosphate on glucose-stimulated insulin secretion in the mouse.
It has been demonstrated that D-myo-inositol-1,2,6-trisphosphate (PP56) antagonizes the effect of neuropeptide Y (NPY) in guinea pig basilar arteries. NPY is known to inhibit insulin secretion. We therefore examined whether PP56 is a NPY antagonist also on insulin secretion. Unanaesthetized mice were injected intraperitoneally with PP56. It was found that the plasma insulin response to a subsequent intravenous glucose challenge (500 mg/kg) was inhibited by PP56 at 20 but not at 2 mg/kg. Also NPY (8.5 nmol/kg) inhibited the glucose-induced increase in plasma insulin levels. When given together, PP56 and NPY exerted additive inhibitory effect. Thus, PP56 is not a NPY-antagonist on insulin secretion, but rather exerts a NPY-like effect. Furthermore, in isolated mouse islets, PP56 at 100 nmol/l, but not at lower dose levels, inhibited glucose (11.1 mM)-stimulated insulin secretion. Hence, PP-56 inhibits glucose-stimulated insulin secretion by a direct effect on the pancreatic islets.
Ahrén
B
B
Department of Surgery, Lund University, Sweden.
D000818:Animals; D003864:Depression, Chemical; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007295:Inositol Phosphates / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors*; D012636:Secretory Rate / Q000187:drug effects
D007295:Inositol Phosphates; D007328:Insulin; D009478:Neuropeptide Y; D005947:Glucose; C059368:atrinositol