Effect of 2-hydroxyoestradiol on insulin secretion in normal rat pancreatic islets.

ETCHEGOYEN, G.S.; BORELLI, M.I.; GAGLIARDINO, J.J.; ROSSI, J.P.F.C.

DIABETES & METABOLISM

Masson

Lugar: Paris; Año: 1998 p. 428 - 433

1262-3636

glucose-induced insulin secretion was evaluated in pancreatic islets isolatedfrom normal rats by collagenase digestion and incubated in KRBbuffer. Insulin output in response to either 3.3 or 16.6 mM glucose wasmeasured by radioimmunoassay in the absence or presence of differentconcentrations of 2-OHE2, norepinephrine (NE), or oestradiol. Islets werealso incubated with 2-OHE2, NE, or oestradiol plus a fixed concentration(1 μM) of the á2-adrenergic-receptor blocking agent yohimbine. The resultsshowed that 2-OHE2, oestradiol and NE within a range of 0.1 to20 μM inhibited glucose-induced insulin secretion in a dose-dependentmanner : Ki (μM) : 0.04 ± 0.0001, 0.04 ± 0.0002, and 0.01 ± 9.1 E – 6 respectively.This suppression was significantly reversed by yohimbine. Contraryto NE and 2-OHE2, oestradiol at lower concentrations (increasingwithin a range of 0.001 to 0.05 μM) in incubation medium in the sameexperimental conditions had a significant stimulatory effect on insulinsecretion. Thus, it would appeart that catecholoestrogens suppress isletinsulin release via á2-adrenergic receptors, which suggests that oestrogensmay exert a dual modulatory effect on insulin secretion by enhancingrelease via direct interaction with the cytosolic-oestrogen receptorand inhibiting release after their local hydroxylation and the interaction oftheir new catechol moiety with á2-adrenergic receptors. Our results suggestthat these compounds may play a complementary role to CAs asnegative modulators, and they also provide a broader scope for understandingthe effect of oestrogens and/or their metabolites in the control ofendocrine functions other than those related to reproduction. Diabetes &Metabolism 1998, 24, 428-433.Key-words: insulin secretion, islets, catecholoestrogens, 2-hydroxy