Correlation between Ca2+-ATPase activity of rat islet cells and insulin secretion

Abstract

Using medium with a low ionic strength, a low concentration of Ca2+ and Mg2+ and devoid of K+, we have measured Ca(2+)-ATPase activity in the homogenates of rat islets preincubated for 3 min with several hormones in the presence of 3.3 mmol glucose/l. Insulin secretion was also measured in islets incubated for 5 min under identical experimental conditions. Islets preincubated with glucose (3.3 mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11 nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those preincubated with only 3.3 mmol glucose/l. All these hormones increased the release of insulin significantly. Dexamethasone (0.1 mumol/l) and somatostatin (1.2 mumol/l) enhanced the Ca(2+)-ATPase activity while adrenaline (10 mumol/l) did not produce any significant effect on the activity of the enzyme. These hormones decreased the release of insulin significantly. These results demonstrated that islet Ca(2+)-ATPase activity was modulated by the hormones tested. Their inhibitory or enhancing effect seemed to be related to their effect on insulin secretion; i.e. those which stimulated the secretion of insulin inhibited the activity of the enzyme and vice versa. Hence, their effect on insulin secretion may be due, in part, to their effect on enzyme activity and consequently on the concentration of cytosolic Ca2+. These results reinforce the assumption that Ca(2+)-ATPase activity participates in the physiological regulation of insulin secretion, being one of the cellular targets for several agents which affect this process.

An overview of Argentine contributions to diabetes research in the decade of the 1990s

“…With this model, the authors definitively showed that glucose and other insulin secretagogues decreased islet PMCA activity while it was enhanced by insulin secretion blockers59–61. Several hormones and drugs also modulate islet PMCA activity as well as proton concentration in the medium60–62. Thus, it was suggested that positive and negative modulation of PMCA might play a role in switching on and off the mechanism for the intracellular Ca 2+ signal regulation of different B‐cell functions, such as insulin secretion.…”

“…In a cooperative study, researchers from CENEXA and IQUIFIB developed a model to study the properties of plasma membrane Ca 2+ ‐ATPase (PMCA) activity in homogenates of isolated pancreatic islets58. With this model, the authors definitively showed that glucose and other insulin secretagogues decreased islet PMCA activity while it was enhanced by insulin secretion blockers59–61. Several hormones and drugs also modulate islet PMCA activity as well as proton concentration in the medium60–62.…”