CONJOINT IGF-I AND INSULIN INFUSION SHOWS DIVERSE INTERACTIVE EFFECTSIN DIABETIC RATS

Studies in diabetic rodents and humans provide evidence that IGF-I may alleviate the diabetic state and insulin resistance to some degree. T o assess the efficacy of IGFs as an adjunct treatment with insulin in diabetes, we infused IGF-I or des(1-3)IGF-I for 7 days at 0, 10.7, 26. 7, and 66.8 nmol/day to streptozotocin-induced diabetic rats in conjun ction with infusions of 0, 2.2, 5.6, or 14 nmol/day insulin, Both insu lin and des(1-3)IGF-I increased body weight gain by 7 g/day compared w ith controls (1.2 g/day), but there was no additive effect, However, f or nitrogen retention, the effects of des(1-3)IGF-I were additive with those of 2.2 nmol/day insulin. Des(1-3)IGF-I was two- to threefold mo re potent than IGF-I. At comparable rates of total nitrogen retention, carcass nitrogen retention was similar to 35% higher with insulin tha n with IGF treatment, indicating a differential tissue response. IGFs did not alter carcass fat content, Des(1-3)IGF-I increased Liver glyco gen additively with insulin but reduced glucosuria only when given wit h 5.6 nmol insulin per day, indicating the possibility of a facilitato ry effect, perhaps via increased insulin sensitivity. Insulin was 10- to 25-fold more potent in these glucoregulatory actions, Differential effects of the hormones were also observed for kidney, liver, and thym us weights. We conclude that IGFs and especially the more potent des(1 -3)IGF-I may have a role as an adjunct to insulin therapy in diabetic patients.