PLASMA LEPTIN IN DIABETIC AND INSULIN-TREATED DIABETIC AND NORMAL RATS

Adipose tissue leptin mRNA levels are decreased by food deprivation or induction of insulin-deficient diabetes. To determine whether plasma leptin concentrations are similarly affected, whether treatment of dia betes with insulin restores plasma leptin, and whether this requires r estoration of body weight (lost as a result of diabetes) and/or normal ization of glycemia, we measured plasma leptin concentrations in contr ol, untreated streptozotocin (STZ)-diabetic, and insulin-treated STZ-d iabetic rats. Plasma leptin was markedly reduced in untreated STZ-diab etic rats. Insulin treatment for 4 to 17 days increased plasma leptin approximately twofold above control levels, However, despite the hyper leptinemia, insulin-treated diabetic rats gained weight at a rate equa l to that of sham-treated controls. Epididymal adipose tissue leptin m RNA levels in 17-day insulin-treated diabetic rats were equal to but d id not exceed sham-control levels, unlike plasma leptin. Plasma glucos e concentrations in insulin-treated STZ-diabetic rats were lower than in sham controls. Therefore, to determine whether hypoglycemia may be important in increasing plasma leptin, we measured plasma leptin level s in diabetic rats infused with insulin for 3 hours along with a varia ble-rate glucose infusion targeting glycemia to 200 or 40 mg/100 mt. P lasma leptin rapidly increased in these rats irrespective of target gl ycemia. Plasma leptin also increased rapidly in normal rats infused wi th insulin and glucose (target glycemia, 200 mg/100 mt). We conclude t hat plasma leptin concentrations are markedly reduced under conditions of insulin deficiency and rapidly increased by insulin treatment. The increase in plasma leptin does not require restoration of body weight and, under glucose clamp conditions, does not depend on target glycem ia. Hyperleptinemia in insulin-treated diabetic rats is not explained on the basis of steady-state leptin mRNA levels, at least as reflected in epididymal fat. Copyright (C) 1998 by W.B. Saunders Company.