In vivo fluorescence microscopy of blood flow in mouse pancreatic islets: adrenergic effects in lean and obese-hyperglycemic mice.

The microcirculation in the islets of Langerhans was examined by fluorescence microscopy in living mice injected with fluorescent dextran. The islet capillary network was denser and more tortuously arranged in obese-hyperglycemic (ob/ob) mice than in lean controls. Injection of norepinephrine (0.5-4.0 micrograms/kg body wt) immediately led to a pronounced inhibition of islet blood flow in ob/ob mice. In experiments with lean mice less striking effects were seen. With as high a dose as 20 micrograms norepinephrine/kg body wt only a slight retardation and very brief stop of the flow occurred. The inhibition in ob/ob mice was blocked by phentolamine, indicating that the norepinephrine-induced inhibition was mediated by alpha-adrenoceptors. The alpha-2-adrenoceptor agonist, clonidine, had no effect on islet blood flow, suggesting that the effect of norepinephrine was due to alpha-1-adrenoceptor stimulation. It is concluded that in the living animal norepinephrine inhibits insulin secretion from the pancreas by a twofold mechanism involving inhibition of exocytosis (alpha-2-receptors on the beta-cells) as well as retardation of blood flow (alpha-1-receptors on blood vessels).