Leptin inhibits insulin binding in isolated rat adipocytes

Abstract

Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', 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 been shown to be related to insulin sensitivity independent of body fat content, suggesting that the hyperleptinemia found in obesity could contribute to the insulin resistance. We investigated the effects of leptin on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptake of 125I-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced total insulin binding in isolated adipocytes by 19% (P < 0.05). Analysis of displacement curve binding data suggested that leptin reduced maximal insulin binding in a dose-dependent manner, but had no significant effect on the affinity of insulin for its binding site. We conclude that leptin directly inhibited insulin binding by adipocytes, and the role of leptin in the development of insulin resistance in obese individuals requires further investigation.

Is there a relationship between leptin and insulin sensitivity independent of obesity?A population-based study in the Indian Ocean nation of Mauritius

“…Alternatively, leptin itself may have an important role in the determination of insulin resistance in the liver, 45 or through interactions with the insulin receptor. 46 Our ®ndings of a strong association between leptin and a marker for insulin sensitivity independent of obesity suggest an important role for leptin in human metabolism. Further studies on the dynamics of the relationship between leptin, insulin and adipose tissue are required to clarify the underlying importance of leptin.…”

“…In the Israeli Sand rat (Psammomys obesus), a model of Type 2 diabetes, leptin has been reported to inhibit insulin binding to adipocyte insulin receptors, offering another mechanism whereby hyperleptinaemia could contribute to insulin resistance in obesity. 46 At the genetic level, the leptin receptor and acute insulin response loci appear to be closely co-localised on chromosome 1, as demonstrated in Pima Indians. 47 It has been suggested therefore, that the leptin receptor gene could play a secondary role in regulation of the acute insulin response (AIR), with high leptin levels down-regulating the receptor gene and diminishing AIR, which may in turn have implications for insulinaemia and insulin sensitivity.…”

Early events involved in the development of insulin resistance in Zucker fatty rat

“…23 On the other hand, some contradictory reports demonstrated that leptin-impaired insulin action and led to insulin resistance. 5,24 A recent study reported that leptin has additive effects with insulin in inhibiting phosphorylase and stimulating glycogen storage in hepatocytes, indicating that the primary action of leptin in hepatocytes is to enhance glycogen storage. 25 In the present study, the wet weight and the glycogen content of liver had already increased in the ZFR group at 6 weeks of age.…”

Glucemia y concentraciones de insulina en sangre de ratas Wistar sometidas a dieta alta en grasa y a tratamiento con péptidos miméticos de leptina

“…Los estudios en ratones knock out para el gen de leptina demostraron una asociación entre leptina, obesidad y otras secuelas metabólicas, tales como hiperfagia e hiperglucemia (16,17); posteriormente, se realizaron diversos estudios que, además de asociarla con obesidad tanto en humanos como en ratas, la relacionan con cambios en las concentraciones y expresión de la insulina, lo cual podría explicar la fisiología y patología de la diabetes mellitus no insulino dependiente en la obesidad (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35); algunos de estos estudios sustentan sus conclusiones en lo siguiente: 1) Durante la pérdida de peso se observan disminuciones en la leptina con reducción en las concentraciones de insulina e independientemente de los cambios de adiposidad (21,26).…”

“…Los investigadores que indican un efecto de la insulina sobre la leptina proponen como soporte los siguientes aspectos: 1) se menciona que en la resistencia a la insulina las concentraciones de leptina son elevadas independientemente del grado de adiposidad (25); 2) en los estudios in vitro de adipocitos, la insulina estimula la expresión y secreción de la leptina; uno de los pasos para este estimulo parece ser la activación de la fosfodiesterasa III por la insulina, la norepinefrina y otras hormonas lipolíticas que competitivamente parecen coregular el efecto que ejerce la insulina sobre la leptina por activación del sistema adenilato-ciclasa (5,28,36).…”