Fig. 5.

Hyperleptinemia increases plasma IGF-1 and IGF-1 action on skeletal muscle, while restoring linear growth in severely insulin-deficient rats. Comparisons of plasma IGF-1 (A) and liver IGF-1 mRNA (B) 30 days after treatment and phosphorylated IGF-1 receptor (P-IGF-1R) in skeletal muscle (C) 3 days after treatment (densitometric units) in untreated (□) (n = 4) and Adv-leptin-treated (■) (n = 4) double-dose-STZ-diabetic rats. (D) Appearance of a nondiabetic normal lean wild-type Zucker Diabetic Fatty (+/+) rat, a double-dose-STZ-diabetic littermate treated with Adv-leptin, and an untreated diabetic littermate. Note that, although both the leptinized and the untreated diabetic rats are slimmer than the nondiabetic wild-type control, the length of the leptinized rat is almost normal. Thus, the growth inhibition caused by insulin deficiency was corrected without insulin replacement.