LEPTIN INHIBITS INSULIN BINDING IN ISOLATED RAT ADIPOCYTES

Leptin is secreted from adipose tissue, and is thought to act as a 'li postat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis. In addition, plasma leptin concentrations have bee n shown to be related to insulin sensitivity independent of body fat c ontent, suggesting that the hyperleptinemia found in obesity could con tribute to the insulin resistance. We investigated the effects of lept in on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptak e of I-125-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced to tal insulin binding in isolated adipocytes by 19% (P<0.05). Analysis o f displacement curve binding data suggested that leptin reduced maxima l insulin binding in a dose-dependent manner, but had no significant e ffect on the affinity of insulin for its binding site. We conclude tha t leptin directly inhibited insulin binding by adipocytes, and the rol e of leptin in the development of insulin resistance in obese individu als requires further investigation.