Dual action of mn++ upon the secretion of insulin and glucagon from the isolated, perfused canine pancreas. Possible interactions with ca++.
Since Mn++ apparently interferes with excitation-contraction coupling by both reducing inward movement of Ca++ across the cell membrane and by displacing Ca++ from an intracellular store, studies were performed in the isolated, perfused canine pancreas to elucidate the existence of a similar effect in stimulus-secretion coupling and to draw comparisons with the effect of Mg++, which antagonizes Ca++ at the cell membrane. The results show: 1. than Mn++ (0.05, 0.125, and 0.25 mmol/l) inhibits the release of insulin and glucagon in a dose dependent fashion during the first 3-4 min of infusion followed by a dose-dependent increase in hormone release, the 'escape phase'. 2. The inhibitory action of Mn++ (0.25 mmol/l) upon release of both hormones is progressively counteracted when perfusate calcium is increased from 0.7 to 1.3 to 5.0 mmol/l. 3. Mg++ (5 mmol/l) inhibits the release of both hormones with no sign of an 'escape phase'. 4. Mn++ (0.5 mmol/l) during calcium depletion causes a gradual stimulation of the release of both hormones. The dual action of Mn++ upon hormone release from the endocrine pancreas suggests that Mn++ can cross the cell membrane and can interfere with stimulus-secretion coupling both at the membrane level, by competitively inhibiting the Ca++ influx, and at some intracellular level by releasing calcium from an intracellular store.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008274:Magnesium / Q000378:metabolism; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism*; D010477:Perfusion; D012636:Secretory Rate / Q000187:drug effects*; D013268:Stimulation, Chemical
D007328:Insulin; D008345:Manganese; D005934:Glucagon; D008274:Magnesium; D002118:Calcium