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Regulatory effects of insulin, somatostatin and cholecystokinin on amino acid transport in the isolated perfused rat pancreas have been studied using a rapid dual isotope dilution technique. Uni-directional L-serine transport (15 s) was quantified relative to an extracellular tracer D-mannitol over a wide range of substrate concentrations. In pancreata perfused with 2.5 mmol/l D-glucose, a weighted nonlinear regression analysis of overall transport indicated an apparent Km = 14.4 +/- 1.6 mmol/l and Vmax = 25.9 +/- 1.4 mumol.min-1.g-1 (n = 6). Although L-serine transport was stimulated during perfusion with 100 microU/ml bovine insulin, endogenous insulin (7-25 ng.min-1.g-1) released during continuous perfusion with either 8.8 mmol/l or 16.8 mmol/l D-glucose had no such effect. Exogenous somatostatin-14 (250 pg/ml) or cholecystokinin octapeptide (CCK-8, 3 x 10(-11) mol/l) appeared to increase only the Km for transport. Only CCK-8 evoked a notable protein output (2.9 +/- 0.3 mg.30 min-1.g-1) and juice flow (68 +/- 10 microliters.30 min-1.g-1, n = 3) from the exocrine pancreas. When pancreata were perfused with bovine insulin (100 microU/ml) and somatostatin-14 (250 pg/ml), the stimulatory action of exogenous insulin on L-serine transport was abolished. If endogenous insulin and somatostatin, released concurrently in response to 16.8 mmol/l D-glucose, were conveyed to the exocrine epithelium via an islet-acinar portal axis, it is conceivable that somatostatin modulates the stimulatory action of insulin on basolateral amino acid transport in the exocrine pancreas.

diabetologia

Paradoxical effects of endogenous and exogenous insulin on amino acid transport activity in the isolated rat pancreas: somatostatin-14 inhibits insulin action