The characteristics of β-adrenergic binding sites on pancreatic islets of Langerhans

Abstract

The sympathetic nervous system is believed to play a part in the control of insulin release from the pancreatic islets of Langerhans. Stimulation of alpha-adrenoceptors is thought to inhibit the release of insulin whereas stimulation of beta-adrenoceptors enhances insulin release. The present experiments were conducted to establish the existence of beta-adrenergic receptors on guinea-pig and rat islet cells and to quantify them using the selective beta-adrenergic ligands [3H]dihydroalprenolol (DHA) and [125I]cyanoiodopindolol (CYP). Guinea-pig islets had 62 fmol beta-adrenoceptors/mg protein using [3H]DHA, corresponding to 43,700 binding sites/cell and 25 fmol beta-adrenoceptors/mg protein using [125I]CYP, corresponding to 17,400 sites/cell. Rat islet cells were found to have 4.6 fmol beta-adrenoceptors/mg protein using [125I]CYP, corresponding to 7200 sites/cell. Adenylate cyclase activation exhibited a positive dose-response relationship when exposed to the beta-adrenoceptor agonist isoprenaline, with a maximum response (190 +/- 21% above basal) at 10 mumol isoprenaline/l. This response was abolished with 1 mumol/l of the beta-adrenergic antagonist l-alprenolol. Insulin secretion in the presence of 10 mmol glucose/l, but in the absence of the alpha-adrenoceptor blocker phentolamine, was not affected by 10 mumol isoprenaline/l. However, perifusion experiments showed that secretion of insulin from isolated rat islets in the presence of 10 mmol glucose/l was significantly increased (332%) by 10 mumol isoprenaline/l in the presence of 10 mumol phentolamine/l. These results suggest that binding of selective radiolabelled ligands occurs to beta-adrenergic receptors on the B cell surface of the islets of Langerhans, and that these receptors are functionally coupled to insulin secretion through modulation of adenylate cyclase activity.

Lipid infusion lowers sympathetic nervous activity and leads to increased β-cell responsiveness to glucose

“…This result suggests that the insulin stimulating β-adrenergic pathway is not involved in the β-cell hyperresponsiveness to glucose in our model. This is in keeping with the 100-fold lower number of β-adrenoreceptors compared with α-adrenoreceptors on β-cell surface (30,31) and is in agreement with the fact that α-adrenergic control of insulin secretion predominates over the β-adrenergic one in vivo (8).…”

Fatty Acid Signaling in the Hypothalamus and the Neural Control of Insulin Secretion

“…This result suggests that the insulin stimulating ␤-adrenergic pathway was not involved in the ␤-cell hyperresponsiveness to glucose in our model. This is in keeping with the 100-fold lower number of ␤-adrenoceptors compared with ␣-adrenoceptors on the ␤-cell surface (26,27) and is in agreement with the fact that ␣-adrenergic control of insulin secretion predominates over the ␤-adrenergic one in vivo (28). We have also demonstrated that these findings in rats are relevant to humans, where 48-h intravenous lipid infusion in healthy subjects also leads to glucose-induced insulin hypersecretion in association with a decrease in plasma norepinephrine concentration and urinary excretion, as an indirect measurement of sympathetic nervous system activity (29).…”

Pharmacological Agents That Directly Modulate Insulin Secretion

“…There is physiologic and pharmacologic evidence for the presence of inhibitory and stimulatory adrenoreceptors on the ␤-cell. The inhibitory ␣-adrenoreceptor has been characterized as being of the ␣ 2 -subtype (Cherksey et al, 1983) and the stimulatory ␤-adrenoreceptor as the ␤ 2 -subtype (Fyles et al, 1986). The ␣ 2 -subtype is coupled to G i /G o , and the ␤ 2 is coupled to the G s protein.…”