Catecholamine inhibition of Ca²⁺‐induced insulin secretion from electrically permeabilised islets of Langerhans

Abstract

Noradrenaline (1-10 gM) inhibited Ca 2 +-induced insulin secretion from electrically permeabilised islets of Langerhans with an efficacy similar to that for inhibition of glucose-induced insulin secretion from intact islets. The inhibition of insulin secretion from permeabilised islets was blocked by the ~-adrenoreceptor antagonist, yohimbine. Adenosine Y,5'-cyclic monophosphate (cAMP) did not relieve the noradrenaline inhibition of Ca 2 +-induced secretion from the permeabilised islets, although noradrenaline did not affect the secretory responses to cAMP at substimulatory (50 nM) concentrations of Ca 2 +. These results suggest that catecholamines do not inhibit insulin secretion solely by reducing B-cell adenylate cyclase activity, and imply that one site of action of noradrenaline is at a late stage in the secretory process.

Noradrenaline inhibition of Ca2+ channels and secretion in single patch‐clamped insulinoma cells

“…A direct inhibitory action on the secretory apparatus, however, is emerging as a general mechanism by which hormones and neurotransmitters inhibit release from both nerve terminals [1,2,[4][5][6] and neuroendocrine cells [3,[9][10][11][12]. Furthermore, there is evidence in both nerve terminals [2] and RINm5F cells [35] that not only the hormonal inhibition of release, but also its stimulation, could be achieved by the modulation of distal steps of the secretory process, downstream from second messenger production.…”

“…In relation to the adrenergic inhibition of insulin secretion from pancreatic beta cells, both inhibition of voltage-operated calcium channels (VOCCs) [7,8] and direct effects on the secretory apparatus have been demonstrated [9][10][11][12]. However, while the modulation of calcium channels is mainly studied at the single cell level, insulin release is usually studied from cell populations, under experimental conditions that differ dramatically in terms of membrane potential, ionic composition of the buffers and time course.…”

Expression of the Two Isoforms of the Vesicular Monoamine Transporter (VMAT1 and VMAT2) in the Endocrine Pancreas and Pancreatic Endocrine Tumors

“…Expression of VMAT2 is an indication of vesicular accumulation of monoamines, which are most likely released together with insulin from beta-cells. The physiological action of monoamines such as histamine, norepinephrine, dopamine and serotonin on the secretion of islet hormones is well documented (Lindstrom and Sehlin 1983;Ahren and Lundquist 1985;Jones et al 1987;Sener et al 1990;Persaud et al 1993;Cable et al 1995;Sjoholm 1995;Coulie et al 1998;Yajima et al 2001). Previous studies on the presence of monoamines, monoamine-synthesizing enzymes, and monoamine uptake in the islets of the non-primate pancreas (rat, mouse, hamster, and guinea pig) using various histochemical and chemical methods have yielded widely differing results (Mahony and Feldman 1977;Ahren and Lundquist 1985;Lundquist et al 1989;Cetin 1992;Iturriza and Thibault 1993;Teitelman et al 1993;Furuzawa et al 1994;Barbosa et al 1998).…”

Proteomic exploration of pancreatic islets in mice null for the α2A adrenergic receptor

“…For example, regulation of cAMP content cannot explain 2A AR-mediated inhibition of insulin release from pancreatic cells, since 2 AR agonists inhibit insulin release even when dibutyryl cAMP is the secretagogue (Rabinovitch et al 1978, Ullrich & Wollheim 1984, indicating that suppression of cAMP production cannot be the principal mechanism for 2A AR modulation of insulin release (Debuyser et al 1991, Sharp 1996. Similarly, although insulin secretion can be inhibited by G-protein mediated direct regulation of K + and Ca 2+ channels (Nilsson et al 1989, Drews et al 1990, Debuyser et al 1991, it is also observed that 2 AR agonists, along with somatostatin and galanin, can inhibit both ionomycin-induced insulin secretion and secretion in permeabilized cells where transmembrane potential and ionic gradients are disrupted (Jones et al 1987, Ullrich & Wollheim 1988, 1989b, Ullrich et al 1990, Lang et al 1995. So it is unlikely 2 AR activation of K + currents or suppression of Ca 2+ currents can fully account for 2 AR attenuation of insulin release.…”