Impact of interleukin-6 on the glucose metabolic capacity in rat liver

Abstract

The actute phase reaction mediated by the proinXammatory cytokine IL6 initiates a number of metabolic changes in the liver, which may contribute to the pathogenesis of the septic shock during prolonged exposition. Here, the impact of IL6 on the hepatic glucose providing capacity was studied by monitoring glycogen degradation and the expression of the gluconeogenic phosphoenolpyruvate carboxykinase (PCK1) in rat livers during the daily feeding rhythm. Eight hours after i.p. injection of IL6, mRNA levels of 2-macroglobulin, a prominent acute phase reactant in rat liver, were elevated as shown by Northern blot analysis and in situ hybridization (ISH). PCK1 mRNA levels were decreased by IL6 to 50% of levels in untreated animals due to the reduction of PCK1 mRNA in the periportal zone of the liver as shown by ISH. PCK1 enzyme activity was not aVected by IL6. Glycogen degradation was accelerated by IL6, which led to nearly complete depletion of glycogen pools in periportal areas 8 h after IL6 injection. This was very likely due to inhibition of glycogen pool replenishment. Thus, the depletion of glycogen stores in the liver might contribute to the impairment of hepatic glucose production during prolonged acute phase challenge.

The Effects of Interleukin-6 and Cytokine-Induced Neutrophil Chemoattractant-1 on .ALPHA.2-Macroglobulin Production in Rats

“…IL-6 and IL-8 are known to regulate the synthesis of acute phase proteins in humans [2-9, 19, 24, 28, 29]. Specifically, it was reported that expression of the α2M gene was regulated by IL-6 [10,14,20]. IL-8 has not been isolated from rats, and CINC-1 is considered to be the rat counterpart of human IL-8 [25,26].…”

“…Procedure of ELISA: Rabbit anti-rat α2M antibody was adsorbed to microtiter wells by incubating 100 µl of antibody in 0.05 M sodium bicarbonate buffer (pH 9.6) per well at room temperature for 1 h. After blocking with 200 µl/well of 1% bovine serum albumin in sodium bicarbonate buffer (pH 9.6), ELISA plates were incubated at 37°C for 1 h and rinsed with phosphate-buffered saline (PBS, pH 7.2) containing 0.1% polyoxyethylene (20) sorbitan monolaurate (Wako Pure Chemical Industries, Ltd.). Standard sera with a known α2M concentration or sample sera were then added at 100 µl/well.…”

IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise

“…Studies using cultured rat hepatocytes showed that incubation with IL-6 attenuated glucagon-induced Pepck (also known as Pck1) expression [4] or inhibited dexamethasone/cAMP-induced Pepck and G6pase (also known as G6pc) expression [5]. Intraperitoneal application of IL-6 inhibited the increase in Pepck mRNA during the initial phase of fasting in rats [6]. Mice secreting IL-6 from injected tumours had decreased G6Pase activity and mRNA levels in the liver, while the activity of PEPCK was not affected [7].…”

Macroglobulin signaling system

“…УЧАСТИЕ ССМ В ЛИПИДНОМ ОБМЕНЕ. Введение ИЛ-6 крысам активирует в гепатоцитах биосинтез МГ при одновременном блокировании гена фосфоенолпируваткарбоксикиназы [40]. МГ регулирует дифференцировку преадипоцитов в зрелые адипоциты.…”