Insulin resistance in experimental alcohol‐induced liver disease

Abstract

Chronic ethanol-induced liver injury causes insulin resistance with inhibition of insulin-responsive genes needed for metabolism, remodeling, and regeneration. In contrast, the IGF-I and IGF-II signaling mechanisms remain relatively preserved, suggesting that insulin-regulated hepatic functions may be selectively vulnerable to the toxic effects of ethanol.

Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice

“…However, in the present study, ethanol was not able to modify this effect despite being widely described that the chronic exposure to ethanol leads to an increase in hepatic lipid content (de la Monte et al, 2008;Pritchard and Nagy, 2005).…”

Metabolic syndrome, diabetes, and hyperuricemia

“…been associated with a lower risk of type 2 diabetes [51,52], and is associated with decreased insulin resistance independent of BMI [53]. By contrast, chronic alcohol-related liver disease was found to be associated with increased expression of insulin [54], and there is evidence that chronic high-level ethanol consumption inhibits DNA synthesis and regenerative and reparative capacities of the liver, which may be due to inhibition of insulin signaling [55]. Moderate alcohol consumption may thus be protective against insulin resistance and the development of type 2 diabetes, whereas high intake seems to increase the risk.…”

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

“…Epidemiological data show that nearly 80% of heavy drinkers with ALD also smoke tobacco [7,8,9,10]. Our interest in analyzing the contributions of tobacco smoke and related toxins to ALD stems from earlier studies showing that limited lowlevel exposures to nitrosamines such as streptozotocin and N-nitrosodiethylamine cause steatohepatitis with hepatic insulin resistance, oxidative and ER stress, and lipid dyshomeostasis [11,12], similar to the effects of alcohol [13,14]. In a recent study designed to assess differential adverse hepatic effects of alcohol and the tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), we demonstrated independent and additive effects of alcohol and NNK in relation to histopathological, ultrastructural, molecular, and signal transduction abnormalities associated with steatohepatitis [15].…”

“…Although ALD is driven by insulin resistance [13,16], inflammation [17], and oxidative and endoplasmic reticulum stress [16,18], each of these pathogenic mediators can be linked to dysregulated lipid metabolism [19,20]. In this regard, ALD and other forms of steatohepatitis are marked by altered lipid profiles, including those corresponding sphingolipids, particularly ceramides [14,16,19,20,21], and membrane phospholipids [22,23,24].…”