Jacqueline Marchand

Possible Role of a Microtubular-Microfilamentous System in Glucagon Secretion

SummaryThe effects of a microfilament-modifier (cytochalasin B), of mitotic spindle-inhibitors (colchicine and vinblastine) and of a microtubule-stabilizer (D2O) on glucagon secretion were studied in vitro, using pieces of pancreas from duct-ligated rats. Cytochalasin B (10 μg/ ml) potentiated arginine-induced glucagon release, but was without effect on unstimulated glucagon release. Colchicine (10−4M) and vinblastine (10−4M) similarly stimulated arginine-induced glucacon release; colchicine did not affect unstimulated glucagon release. Deuterium oxide (100%, v/v) reversibly inhibited arginine-induced glucagon secretion. If it is assumed that the above mentioned drugs specifically interact with microfilaments and microtubules in the A2 cells, our results would suggest that a microtubular-microfilamentous system indeed participates in the process of glucagon secretion. The intimate mechanism by which such a system may apparently play both a restrictive and effector role in glucagon release remains, however, to be elucidated.

Role of glucose and insulin in the dynamic regulation of glucagon release by the perfused rat pancreas

SummaryThe effect of glucose upon the release of glucagon and insulin from the perfused rat pancreas in vitro was studied by varying both the concentration of glucose (from 3.3 to 4.6, 8.5, or 11.1 mmol/l) and the time of exposure to an elevated concentration of the sugar (5, 10 or 23 min). The results suggest that the amount of insulin released during the early period of stimulation could contribute to both the speed and extent of the inhibition in glucagon release. The rate of recovery from inhibition in the A cell, however, appeared to be independent of insulin and was related, in a dose-dependent and time-dependent manner, only to the glucose stimulus. It is suggested that a direct effect of glucose upon the A cell is involved in the physiological regulation of glucagon secretion. An indirect effect of glucose, as mediated via insulin release, may contribute to the rapidity and magnitude of inhibition in A cell secretory activity.

Insulin and glucagon release from the ventral and dorsal parts of the perfused pancreas of the rat. Effects of glucose, arginine, glucagon and carbamylcholine

The ventral and the dorsal parts of the rat pancreas were perfused separately via either the superior mesenteric artery (0.6 ml/min) or the coeliac artery (1.4 ml/min). Control perfusions were performed via both arteries (2 ml/min). Expressed relative to the weight of tissue, the insulin content was comparable in the ventral and dorsal parts whereas the glucagon content was 2.5 times lower in the ventral than dorsal part. In comparison to the dorsal or total pancreas, the insulin secretory activity of the ventral pancreas was markedly decreased in response to either an elevation of the glucose concentration or the administration of carbamylcholine or arginine. The difference between the ventral and dorsal response was less marked at low glucose concentrations (3.3 or 7.0 mmol/l) and, possibly, in response to glucagon. In the case of glucagon release, a decreased response of the ventral pancreas was only observed when glucagon output was fully stimulated by the administration of arginine at a low glucose concentration. These results indicate that the B cell in the ventral pancreas responds poorly to several stimuli. There was little evidence to support the involvement of endogenous glucagon in the diminished sensitivity of the ventral B cells.

The Versatile Role of Calcium in Glucagon Release

Data on the interrelationships between calcium and the secretory activity of the A cell are reviewed and discussed. It is postulated that calcium has a multiple role in the secretory activity of the pancreatic A cell. First, a cellular accumulation of calcium may mediate the glucagonotropic action of arginine and of a mixture of pyruvate, fumarate and glutamate. Second, the presence of a sufficient amount of extracellular calcium seems to be a prerequisite for the identification of certain environmental factors, especially glucose in high concentration, by the A cell. Third, under appropriate experimental conditions, e. g. during prolonged exposure to a low glucose level, the accumulation of intracellular calcium may exert a feedback inhibitory effect upon the secretory process.