title: Effect of nicotinic acid-induced insulin resistance on pancreatic B cell function in normal and streptozocin-treated baboons.
abstract: To study the interaction between insulin secretion and insulin action in maintaining glucose homeostasis, we induced experimental insulin resistance in eight normal baboons, in six baboons treated with 40 mg/kg streptozocin (STZ-40), and in six baboons treated with 200 mg/kg streptozocin (STZ-200). Insulin resistance was induced by a 20-d continuous intravenous infusion of nicotinic acid (NA). Normal animals showed compensatory increases in several measures of insulin secretion (fasting insulin [FI], acute insulin response to arginine [AIRarg], acute insulin response to glucose [AIRgluc], and glucose potentiation slope [delta AIRarg/delta G]), with no net change in fasting plasma glucose (FPG) or glycosylated hemoglobin (HbAtc). STZ-40 animals showed compensatory increases in FI, AIRarg, and AIRgluc, but delta AIRarg/delta G failed to compensate. Although FPG remained normal in this group during NA infusion, HbA1c rose significantly. STZ-200 animals failed to show compensatory changes in both AIRgluc and delta AIRarg/delta G, with both HbA1c and FPG rising. These animals showed a paradoxical inhibition of insulin secretion in response to intravenous glucose during NA infusion, at a time when they were hyperglycemic. These data indicate that a significant degree of insulin resistance does not cause hyperglycemia in the presence of normal B cell function but, in animals with reduced B cell mass and superimposed insulin resistance, the degree of hyperglycemia is proportional to the degree of pancreatic B cell dysfunction.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98108.
authors.forename: D K
authors.initials: DK
authors.lastname: McCulloch
authors.forename: S E
authors.initials: SE
authors.lastname: Kahn
authors.forename: M W
authors.initials: MW
authors.lastname: Schwartz
authors.forename: D J
authors.initials: DJ
authors.lastname: Koerker
authors.forename: J P
authors.initials: JP
authors.lastname: Palmer
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D005215:Fasting; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D009525:Niacin / Q000494:pharmacology*; D010215:Papio; D013311:Streptozocin
chemical_list: D007328:Insulin; D009525:Niacin; D013311:Streptozocin; D001120:Arginine; D005947:Glucose