THE EFFECT OF INSULIN-TREATMENT AND OF ISLET TRANSPLANTATION ON THE RESISTANCE ARTERY FUNCTION IN THE STZ-INDUCED DIABETIC RAT

1 This study was designed to investigate the influence of insulin trea tment and islet transplantation on the smooth muscle contractility and endothelium-dependent and independent relaxation of resistance arteri es in the chemically induced streptozotocin (STZ) diabetic rat after 6 -8 weeks, and 12-14 weeks of diabetes, compared to non-diabetic age-ma tched controls. 2 The morphology, and contractile responses to high po tassium physiological salt solution (KPSS), KPSS containing 10(-5) M n oradrenaline (NAK), and concentration-response curves to noradrenaline (NA) of mesenteric resistance arteries were recorded, along with the endothelium-dependent relaxation responses to acetylcholine (ACh) and bradykinin (BK), and endothelium-independent relaxation to sodium nitr oprusside (SNP). Concentration-response curves were then repeated in t he presence of a nitric oxide synthase inhibitor, N-G-nitro-L-arginine (L-NOARG). 3 Insulin-treated diabetic rats in the 12 week study demon strated enhanced vascular contractility to KPSS, NAK and NA, compared to age-matched non-diabetic controls. 4 Incubation with L-NOARG result ed in both a significant increase in maximum contractile response, and sensitivity (pD(2)) to NA in the untreated diabetic group (6 weeks). A significant shift in sensitivity was also seen in the insulin-treate d diabetic group. In the 12 week study, incubation with L-NOARG result ed in an increased maximum contractile response and sensitivity to NA in the insulin-treated diabetics. An increase in sensitivity was also observed in the untreated diabetic group. 5 Endothelium-dependent rela xation to ACh was significantly augmented in the untreated diabetics ( 6-weeks), compared to the control group. In the 12-week study, relaxat ion to both ACh and BK was not significantly different in any of the e xperimental groups when compared to the sham-operated nondiabetic cont rols. 6 Incubation with L-NOARG resulted in a significant attenuation of the maximum relaxation response to ACh and BK in all of the experim ental groups, in the 6- and the 12-week study. 7 There was no signific ant difference in the maximum relaxation response or sensitivity to so dium nitroprusside between the diabetic groups and their age-matched c ontrols in either the 6-week or the 12-week study. 8 The results of th is study suggest an enhanced release of nitric oxide in the early stag es of diabetes, which is more evident in the untreated diabetic rats t han the insulin treated, and appears to normalize as the duration of d iabetes progresses. This study also shows that the alteration in vascu lar reactivity of the resistance arteries can be restored to within no rmal limits by the transplantation of islets of Langerhans, and that i slet transplantation is an effective strategy in the correction of the metabolic abnormalities associated with insulin-dependent diabetes.