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Autocrine regulation of glucose metabolism in pancreatic islets

Center of Experimental and Applied Endocrinology (Universidad Nacional de la Plata-Consejo Nacional de Investigaciones Cientificas y Tecnicas, Pan American Health Organization/World Health Organization Collaborating Center), National University of La Plata School of Medicine, 1900 La Plata, Argentina

Submitted 11 April 2003 ; accepted in final form 16 September 2003

We evaluated the possible autocrine modulatory effect of insulin on glucose metabolism and glucose-induced insulin secretion in islets isolated from normal hamsters. We measured ¹⁴CO₂ and ³H₂O production from D-[U-¹⁴C]glucose and D-[5-³H]glucose, respectively, in islets incubated with 0.6, 3.3, 8.3, and 16.7 mM glucose alone or with 5 or 15 mU/ml insulin, anti-insulin guinea pig serum (1:500), 25 µM nifedipine, or 150 nM wortmannin. Insulin release was measured (radioimmunoassay) in islets incubated with 3.3 or 16.7 mM glucose with or without 75, 150, and 300 nM wortmannin. Insulin significantly enhanced ¹⁴CO₂ and ³H₂O production with 3.3 mM glucose but not with 0.6, 8.3, or 16.7 mM glucose. Addition of anti-insulin serum to the medium with 8.3 and 16.7 mM glucose decreased ¹⁴CO₂ and ³H₂O production significantly. A similar decrease was obtained in islets incubated with 8.3 and 16.7 mM glucose and wortmannin or nifedipine. This latter effect was reversed by adding 15 mU/ml insulin to the medium. Glucose metabolism was almost abolished when islets were incubated in a Ca²⁺-deprived medium, but this effect was not reversed by insulin. No changes were found in ¹⁴CO₂ and ³H₂O production by islets incubated with 3.3 mM glucose and anti-insulin serum, wortmannin, or nifedipine in the media. Addition of wortmannin significantly decreased insulin release induced by 16.7 mM glucose in a dose-dependent manner. Our results suggest that insulin exerts a physiological autocrine stimulatory effect on glucose metabolism in intact islets as well as on glucose-induced insulin release. Such an effect, however, depends on the glucose concentration in the incubation medium.

insulin secretion; autocrine regulation; isolated islets

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