Insulin release is impaired by vitamin D3 deficiency but can be restored by in vivo administration of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. A direct influence of 1,25(OH)2D3 on the B-cell was studied in vitro with islets from 5-wk vitamin D3-deprived rats. This hormone (10(-12) to 10(-6) mol/l) added to the incubation medium had a stimulatory dose-dependent effect on insulin response to 8.3 mmol/l glucose 6 h later. Moreover, perifusion experiments performed after different times of incubation demonstrated that after 6 h 1,25(OH)2D3 increased in particular the first phase of insulin response to 16.7 mmol/l glucose. The 45Ca fluxes, followed in parallel, were never modified by 1,25(OH)2D3 in the absence of glucose but were enhanced during the glucose stimulus, whereas 86Rb fluxes were never affected by 1,25(OH)2D3. These results demonstrated that 1,25(OH)2D3 acts in vitro on B-cells, but with a 6-h delay to potentiate the glucose-induced insulin release, concomitant with intracellular calcium redistribution.

The interference of adrenal hormones with the oestradiol-induced modifications of endocrine pancreatic function remains controversial. For this reason, we compared sham-operated, ovariectomized and adrenalectomized-ovariectomized female rats. In each group, control and 17-beta-oestradiol-treated rats (0.1 mg/day for 14 days) were studied, the latter group being compared with similar rats treated with corticosterone (0.4 mg/day). Oestradiol treatment induced hypoglycaemia and hyperinsulinism in basal and glucose-stimulated states, and hypoglucagonaemia. The presence of adrenal glands was necessary for the full expression of oestradiol effects on pancreatic islet B cells: in adrenalectomized-ovariectomized rats, oestradiol treatment induced an unexpected decrease in insulin response to intravenous glucose, and in pancreatic insulin content. Corticosterone treatment partly restored the oestradiol-induced rise of plasma insulin, and restored the B cell response to intravenous glucose. A permissive action of glucocorticoids may be a prerequisite for the effect of oestrogens on B cells. Since oestrogens by themselves augment the plasma corticosterone level, the insulinotropic effect of oestrogens may be partly mediated by the increase in endogenous corticosteroids. In contrast, oestradiol seems to suppress islet A cell function.

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The effects of progesterone and/or oestradiol treatment on the ultrastructural appearance of the pancreatic B cells has been studied in ovariectomized Wistar rats. A morphometric examination of the numberical density of dark and high granules in the B cells was therefore performed in each group of experimental rats as well as in control (olive oil-injected) rats. In the oestradiol-treated rats, and especially in the rats with combined oestradiol/progesterone treatment, the proportions of light and dark granules in the pancreatic B cells changed, compared with control values, in favour of the light granules. This increase in light granule content was comparable to changes in B cells during a pregnancy and it is suggested that the secretory activity of the B cells increases during pregnancy in a manner similar to that seen during oestradiol treatment.

Ovarian-adrenal interactions on insulin secretion during oestradiol treatment were studied in sham-operated, ovariectomized and adrenalectomized-ovariectomized female rats, the latter thus treated to suppress interference from endogenous hormones. Islets of Langerhans isolated from oestradiol or oestradiol + corticosterone treated and control rats were incubated with various glucose concentrations. Oestradiol treatment enhanced basal and glucose stimulated insulin secretion from sham-operated (+12%) or ovariectomized rats (+24%). This effect disappeared in adrenalectomized-ovariectomized rats but reappeared when adrenalectomized-ovariectomized rats were treated with oestradiol + corticosterone (+37%). A 14-day oestradiol treatment had a trophic effect on total protein content independent of adrenal presence (+14%; +15%; +31%; +23% versus respective control groups). Our data demonstrate that corticosterone is necessary for the stimulating effect of oestradiol on insulin secretion.