Adrenergic Modulation of Basal Insulin Secretion in Man

Abstract

In normal men of varying degrees of adiposity, alphaadrenergic blockade (one-hour intravenous infusion with phentolamine, 0.5 mg./min.) produced a 31 ± 23 per cent (mean ± S.D.) increase (n = 6, p < .02) over basal insulin levels whereas beta-adrenergic blockade (one-hour intravenous infusion with propranolol, 0.08 mg./min.) produced a 38 ± 15 per cent decrease (n = 6, p < .002) from basal insulin levels; basal glucose did not change during either type of blockade. Epinephrine (two-hour intravenous infusion, 6 /tg./min.) produced a 46 ± 8 per cent decrement in basal insulin by 7 ± 4 min. (n = 12, p < .001). This was followed by a period of recovery during which insulin levels rose to control levels by 46 ± 26 minutes and to 166 ± 36 per cent of control (p < .001) by two hours. The nadir of the decrement correlated, with a high degree of statistical significance, with basal insulin values (r = .99, p < .001), and the amount of time required during the recovery phase for insulin levels to rise to control levels correlated highly with the nadir of the decrement (r = .83, p < .001). The epinephrine-induced decrement from basal insulin did not occur in three subjects pretreated with phentolamine but did occur in four subjects pretreated with propranolol. In the four subjects pretreated with propranolol, the mean recovery time during epinephrine infusion was seventy-two minutes, compared to thirty-six minutes for the group receiving epinephrine alone. In four separate studies, propranolol was superimposed after two hours of a three-hour epinephrine infusion had elapsed, and the elevated insulin levels that had developed by two hours promptly fell below basal levels. It is concluded that (1) endogenous adrenergic activity modulates basal insulin secretion; (2) increases in circulating epinephrine prompt a rapid, marked fall in basal insulin which is alpha mediated; and (3) a slower, beta-mediated recovery phase follows during which insulin surpasses basal levels.

Reduced insulin binding to human fat cells following beta-adrenergic stimulation ? experimental evidence and studies in patients with a phaeochromocytoma

“…This is not surprising, however, since the effect of catecholamines on glucose levels in vivo is probably due to several actions such as an a-mediated inhibition of insulin secretion [25], increased hepatic glucose production [26] and reduced peripheral insulin sensitivity and responsiveness [2,3]. In this context, it should also be noted that insulin levels were similar before and after surgery.…”

Elevated heart rate predicts β cell function in non-diabetic individuals: the RISC cohort

“…Islet innervation of adrenergic nerves has been documented for many years (27). A body of evidence in both animals and humans has demonstrated that sympathetic stimulation induces an inhibition of basal and glucose-stimulated insulin secretion (28,29,30).…”

Essential role of the imidazoline moiety in the insulinotropic effect but not the KATP channel-blocking effect of imidazolines; a comparison of the effects of efaroxan and its imidazole analogue, KU14R

“…Originally, antagonism at alpha-adrenoceptors was supposed to be the mechanism of action of the prototypical imidazoline, phentolamine [4,5]. When it became clear that the insulinotropic property of this compound was not due to alpha-antagonism but was related to the presence of an imidazoline moiety [6,7], it was hypothesised that, like other tissues, beta cells express specific imidazoline binding sites [8][9][10].…”