Paradoxical effects of endogenous and exogenous insulin on amino acid transport activity in the isolated rat pancreas: somatostatin-14 inhibits insulin action.
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.
Norman
P S
PS
Physiology, Biomedical Sciences Division, King's College London, UK.
Habara
Y
Y
Mann
G E
GE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology*
D007328:Insulin; D012694:Serine; D013004:Somatostatin; D005947:Glucose; D012844:Sincalide