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Biomedical subjects

R D Milner

Publications and source records attributed to R D Milner.

At least 199 records · Page 11Linked to original sources

The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreas in vitro.

The effect of various inhibitors on insulin release from pieces of rabbit pancreas incubated in vitro was studied. Insulin release was stimulated by glucose (3mg./ml.), leucine (5mm), tolbutamide (200mug./ml.), ouabain (10mum), a raised extracellular K(+) concentration (60mm) and substitution of the Ca(2+) content of the incubation medium by Ba(2+) (2.5mm). (a) Mannoheptulose (6mg./ml.) inhibited glucose-stimulated insulin release only. (b) Anoxia abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide and K(+), but had little or no effect on release stimulated by ouabain or Ba(2+). (c) 2,4-Dinitrophenol (0.25mm) abolished or inhibited insulin release stimulated by glucose, ouabain or Ba(2+). (d) Diazoxide (250mug./ml.) abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba(2+) (0.25 or 1mm). Diazoxide had no effect on insulin release stimulated by Ba(2+) (2.5mm) and potentiated release stimulated by K(+). (e) Adrenaline (1mum) abolished insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba(2+). K(+)-stimulated release was inhibited by adrenaline. (f) Tetrodotoxin (1mum) had no effect on insulin release stimulated by glucose, leucine, tolbutamide, ouabain, K(+) or Ba(2+). (g) Nupercaine (1mm) abolished insulin release stimulated by glucose or Ba(2+).

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The role of sodium and potassium in insulin secretion from rabbit pancreas.

1. Insulin secretion from pieces of rabbit pancreas incubated in vitro was studied in media of different ionic composition and in response to different substances added to the media.2. Experiments were performed which demonstrated that a sodium pump played a role in insulin secretion and that inhibition of the pump by ouabain, or by the omission of extracellular potassium, stimulated insulin secretion.3. A rise in extracellular potassium concentration stimulated insulin secretion independently of changes in the osmolarity or sodium or chloride concentration of the incubation medium.4. The role of extracellular sodium in insulin secretion was investigated. Extracellular sodium was a pre-requisite for insulin secretion stimulated by glucose, glucagon, L-leucine, tolbutamide, potassium or ouabain.5. The presence of 3.3 mM glucose in the incubation medium was not essential for the stimulation of insulin secretion by L-leucine, tolbutamide or ouabain. Glucagon did not stimulate insulin secretion in the presence of 3.3 mM glucose but did so in the presence of 16.5 mM glucose.6. The results obtained in these experiments suggested that a transmembrane sodium flux probably in the beta cell was a fundamental event in the stimulation of insulin secretion by diverse stimuli.

Animals↗

Cations and the secretion of insulin from rabbit pancreas in vitro.

1. Insulin secretion from pieces of rabbit pancreas incubated in vitro was studied in media of different ionic compositions.2. Insulin secretion stimulated by glucose was abolished by removal of calcium from the incubation medium and inhibited by a twofold rise in the calcium concentration to 10.2 m-equiv/l. Removal of magnesium from the medium did not affect glucose-stimulated secretion but a tenfold rise in the extracellular magnesium concentration to 24 m-equiv/l. abolished secretion.3. The replacement of calcium by an equivalent amount of barium (5.1 m-equiv/l.) stimulated insulin secretion. Barium stimulation declined with time and was inhibited by the presence of calcium, 5.1 m-equiv/l., or abolished by the presence of magnesium, 24 m-equiv/l., in the incubation medium.4. The interactions of mono- and divalent cations on insulin secretion were studied by using ouabain or potassium as tools to raise intracellular sodium concentration and barium as a calcium analogue. Ouabain and potassium were effective stimuli only in the presence of calcium, and barium only stimulated insulin secretion in the presence of sodium.5. The results of these experiments suggest that both calcium and sodium must act at the beta cell membrane or enter the cell before insulin release can occur in response to a variety of stimuli.

Animals↗