SEPARATE AND JOINT EFFECTS OF ARGININE AND GLUCOSE ON OVINE FETAL INSULIN-SECRETION

To determine separate and joint effects of increases (Delta) in fetal plasma concentrations of arginine (A(f)) and glucose (G(f)) on fetal i nsulin (I-f) secretion (Delta(f)), 15 late-gestation fetal sheep were given 5-min arginine bolus infusions (40, 86, 144, 201, and 402 mu mol /kg estimated fetal wt) at 90 min of 120 min steady-state glucose clam ps (basal G(f), basal + 0.6 mM G(f), and basal + 1.1 mM G(f)), produci ng absolute and percent increases above basal A(f) of 25.8 +/- 1.3 mu M (+33%), 50.9 +/- 6.3 mu M (+66%), 83.8 +/- 7.1 mu M (+108%), 122.1 /- 9.4 mu M (+156%), and 302.2 +/- 28.2 mu M (+386%), respectively. Ac ute hyperglycemia alone produced an increase above basal I-f of 9 +/- 1 mu U/ml (+80%) and 19 +/- 2 mu U/ml (+170%) after basal + 0.6 mM G(f ) and basal + 1.1 mM G(f), respectively. Increasing values of Delta A( f) showed separate but lesser effects on Delta I-f, which were signifi cant only at very high values of A(f) (>100% above mean normal A(f)) u nless marked hyperglycemia (1.5- to 2-fold normal) was also present, d emonstrating joint effects of Delta A(f) and Delta G(f) on Delta I-f a ccording to a best-fit inverse polynomial response surface. We conclud e that physiological increases in A(f) at normal glucose concentration s are not a potent stimulus to insulin secretion in fetal sheep.