title: Separate and joint effects of arginine and glucose on ovine fetal insulin secretion.
abstract: To determine separate and joint effects of increases (delta) in fetal plasma concentrations of arginine (Af) and glucose (Gf) on fetal insulin (If) secretion (delta If), 15 late-gestation fetal sheep were given 5-min arginine bolus infusions (40, 86, 144, 201, and 402 mumol/kg estimated fetal wt) at 90 min of 120 min steady-state glucose clamps (basal Gf, basal + 0.6 mM Gf, and basal + 1.1 mM Gr), producing absolute and percent increases above basal Af of 25.8 +/- 1.3 microM (+33%), 50.9 +/- 6.3 microM (+66%), 83.8 +/- 7.1 microM (+108%), 122.1 +/- 9.4 microM (+156%), and 302.2 +/- 28.2 microM (+386%), respectively. Acute hyperglycemia alone produced an increase above basal If of 9 +/- I microU/ml (+80%) and 19 +/- 2 microU/ml (+170%) after basal + 0.6 mM Gf and basal + 1.1 mM Gf, respectively. Increasing values of delta Af showed separate but lesser effects on delta If, which were significant only at very high values of Af (> 100% above mean normal Af) unless marked hyperglycemia (1.5- to 2-fold normal) was also present, demonstrating joint effects of delta Af and delta Gf on delta If according to a best-fit inverse polynomial response surface. We conclude that physiological increases in Af at normal glucose concentrations are not a potent-stimulus to insulin secretion in fetal sheep.
authors.affiliation: Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gresores
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Hood
authors.forename: G O
authors.initials: GO
authors.lastname: Zerbe
authors.forename: W W
authors.initials: WW
authors.lastname: Hay
mesh_terms: D000818:Animals; D001120:Arginine / Q000097:blood* / Q000494:pharmacology; D001786:Blood Glucose / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005260:Female; D005312:Fetal Blood; D005333:Fetus / Q000378:metabolism*; D005502:Food; D015309:Glucose Clamp Technique; D006706:Homeostasis; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008954:Models, Biological; D011247:Pregnancy; D012756:Sheep / Q000196:embryology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D001120:Arginine