Possible modulatory effect of endogenous islet catecholamines on insulin secretion.
BACKGROUND: The possible participation of endogenous islet catecholamines (CAs) in the control of insulin secretion was tested. METHODS: Glucose-induced insulin secretion was measured in the presence of 3-Iodo-L-Tyrosine (MIT), a specific inhibitor of tyrosine-hydroxylase activity, in fresh and precultured islets isolated from normal rats. Incubated islets were also used to measure CAs release in the presence of low and high glucose, and the effect of alpha2-(yohimbine [Y] and idazoxan [I]) and alpha1-adrenergic antagonists (prazosin [P] and terazosin [T]) upon insulin secretion elicited by high glucose. RESULTS: Fresh islets incubated with 16.7 mM glucose released significantly more insulin in the presence of 1 &mgr;M MIT (6.66 +/- 0.39 vs 5.01 +/- 0.43 ng/islet/h, p < 0.02), but did not affect significantly the insulin response to low glucose. A similar enhancing effect of MIT upon insulin secretion was obtained using precultured islets devoid of neural cells, but absolute values were lower than those from fresh islets, suggesting that MIT inhibits islet rather than neural tyrosine hydroxylase. CAs concentration in the incubation media of fresh isolated islets was significantly higher in the presence of 16.7 than 3.3 mM glucose: dopamine 1.67 +/- 0.13 vs 0.69 +/- 0.13 pg/islet/h, p < 0.001, and noradrenaline 1.25 +/- 0.17 vs 0.49 +/- 0.04 pg/islet/h, p < 0.02. Y and I enhanced the release of insulin elicited by 16.7 mM glucose while P and T decreased such secretion. CONCLUSION: Our results suggest that islet-originated CAs directly modulate insulin release in a paracrine manner.
Borelli
Maria I
MI
CENEXA - Center of Experimental and Applied Endocrinology (National University of La Plata-National Research Council, PAHO/WHO Collaborating Center), School of Medical Sciences, 60 y 120, 1900 La Plata, Argentina. gagliardino@infovia.com.ar
Gagliardino
Juan J
JJ