REGIONAL BLOOD-FLOW DYNAMICS IN RESPONSE TO INSULIN AND IGF-1 IN DIABETIC ANIMALS

Vascular changes in diabetes characterized by increased contractile or decreased dilator responses have been demonstrated in isolated blood vessels as well as in vivo systems. Previous studies in our laboratory have demonstrated that insulin and insulin like growth factor-1 (IGF- 1) can decrease mean arterial pressure (MAP) and increase blood flow i n vascular beds. In this study we evaluated the regional hemodynamic r esponses to insulin and IGF-1 in normal and diabetic rats. Normal male rats were made diabetic with streptozotocin (55 mg/kg) i.v. and maint ained 60 to 70 days. On the day of the study the rats were anesthetize d with urethane/chloralose. the femoral artery and vein cannulated for blood pressure monitoring and blood sampling or infusion. respectivel y. Pulsed-Doppler now probes were placed around the iliac artery, rena l artery and superior mesenteric artery to monitor blood flow. insulin (16 nmol/kg) was infused as a bolus via the femoral vein and it decre ased the MAP approximately 17% in both normal and diabetic rats. Insul in enhanced vascular now (expressed as conductance) in the iliac and r enal vascular bed but not: the superior mesenteric vascular bed in nor mals. In diabetic rats the flow response to insulin compared to normal s was attenuated in the iliac and renal vascular beds and increased in the superior mesenteric vascular bed. A bolus infusion of IGF-1 (16 n mol/kg) also decreased the MAP in normals and diabetics. increased vas cular now in all three vascular beds in normals but in the diabetics t he response to IGF-1 was attenuated in the iliac, increased in the ren al vascular bed and suppressed in the superior mesenteric vasculature. From these studies we conclude that diabetes is associated with an at tenuated vascular response to insulin and IGF-1 in the iliac and renal vessels while insulin augments and IGF-1 decreases blood flow in the superior mesenteric vasculature.