Differential effects of β-adrenergic agonists on insulin secretion from pancreatic islets isolated from rat and man

Abstract

The selective beta 2-adrenergic agonist clenbuterol was ineffective as a stimulus for insulin secretion when isolated rat pancreatic islets were incubated with glucose at concentrations between 4 and 20 mM. Inclusion of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine led to potentiation of glucose-induced insulin secretion, but did not facilitate stimulation by clenbuterol. Furthermore, maintenance of isolated rat islets for up to 3 days in tissue culture also failed to result in the appearance of a secretory response to beta-agonists. By contrast, clenbuterol induced a dose-dependent increase in insulin release from isolated human islets incubated with 20 mM glucose. Clenbuterol did not increase the basal rate of insulin secretion (4 mM glucose) in human islets. Under perifusion conditions, the secretory response of human islets to clenbuterol was rapid, of similar magnitude to that seen under static incubation conditions and could be sustained for at least 30 min. The increase in insulin secretion induced by clenbuterol was inhibited by propranolol, indicating that the response was mediated by activation of beta-receptors. In support of this, a similar enhancement of glucose-induced insulin secretion was elicited by a different beta 2-agonist, salbutamol, in human islets. The results indicate that the B cells of isolated rat islets are unresponsive to beta-agonists, whereas those of human islets are equipped with functional beta-receptors which can directly influence the rate of insulin secretion.

Insulin resistance in subjects with a history of thyrotoxic periodic paralysis (TPP)

“…Furthermore, there are many studies that support a role for hyperinsulinaemia in the pathogenesis of TPP. First, a nonselective β‐adrenergic blocker, propranolol, which decreases insulin secretion, 10,11 is an effective drug in preventing hypokalaemic paralysis 12 . Second, islet cells require potassium to secrete insulin, thus hypokalaemia during an attack decreases insulin secretion 13 .…”

A comparative analysis of human and mouse islet G-protein coupled receptor expression

“…In fact, mouse and human islets have distinct morphological arrangements, which may impact on their function1011 and several studies comparing the gene expression profiles of human and rodent islets suggest that there are significant differences, including in GPCR expression121314. This has been confirmed functionally in experiments using isolated rodent and human islets where it has been reported that human islets express β-adrenergic receptors that are coupled to elevation of insulin secretion, while β-adrenergic agonists have no effect on insulin release from rat islets15. In addition, MT1 receptors, which are activated by the pineal hormone melatonin, are reported to be expressed by rodent β-cells but not by human β-cells16, and different classes of purinergic receptor regulate intracellular calcium levels in rodent17 and human18 β-cells.…”

Severe Hyperinsulinaemic Hypoglycaemia in a Baby Born to a Mother Taking Oral Ritodrine Therapy for Preterm Labour

“…Newborn lambs infused with ritodrine hydrochloride demonstrate a progressive rise in insulin/glucose, suggesting direct stimulation of pancreatic β-cell secretion [19]. Human pancreatic β-cells are equipped with both α 2 - and β 2 -adrenoceptors which can affect insulin secretion [20, 21]. Ritodrine is a selective β 2 -adrenoceptor agonist activation of whichstimulates adenylate cyclase with resultantincrease in the intracellular cAMP concentration [22].…”