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 diabetes with insulin restores plasma leptin, and whether this requires restoration of body weight (lost as a result of diabetes) and/or normalization of glycemia, we measured plasma leptin concentrations in control, untreated streptozotocin (STZ)-diabetic, and insulin-treated STZ-diabetic rats. Plasma leptin was markedly reduced in untreated STZ-diabetic rats. Insulin treatment for 4 to 17 days increased plasma leptin approximately twofold above control levels. However, despite the hyperleptinemia, insulin-treated diabetic rats gained weight at a rate equal to that of sham-treated controls. Epididymal adipose tissue leptin mRNA levels in 17-day insulin-treated diabetic rats were equal to but did not exceed sham-control levels, unlike plasma leptin. Plasma glucose 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 levels in diabetic rats infused with insulin for 3 hours along with a variable-rate glucose infusion targeting glycemia to 200 or 40 mg/100 mL. Plasma leptin rapidly increased in these rats irrespective of target glycemia. Plasma leptin also increased rapidly in normal rats infused with insulin and glucose (target glycemia, 200 mg/100 mL). We conclude that 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 glycemia. 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.