Effect of nicotinic acid-induced insulin resistance on pancreatic B cell function in normal and streptozocin-treated baboons.
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.
McCulloch
D K
DK
Department of Medicine, University of Washington, Seattle 98108.
Kahn
S E
SE
Schwartz
M W
MW
Koerker
D J
DJ
Palmer
J P
JP
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
D007328:Insulin; D009525:Niacin; D013311:Streptozocin; D001120:Arginine; D005947:Glucose