Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in experimental chronic alcohol-induced steatohepatitis.
AuthorsRamirez T, Longato L, Dostalek M, Tong M, Wands JR, de la Monte SM,
JournalAlcohol Alcohol
PubMed ID22997409
'Chronic alcohol abuse causes steatohepatitis with insulin resistance, which impairs hepatocellular growth, survival and metabolism. However, growing evidence supports the concept that progressive alcohol-related liver injury may be mediated by concurrent mal-signaling through other networks that promote insulin resistance, e.g. pro-inflammatory, pro-ceramide and endoplasmic reticulum (ER) stress cascades. Using the ... More
Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice.
'Diabetes and obesity are metabolic disorders induced by an excessive dietary intake of fat, usually related to inflammation and oxidative stress. The aim of the study is to investigate the effect of the antioxidant coenzyme Q10 (CoQ10) on hepatic metabolic and inflammatory disorders associated with diet-induced obesity and glucose intolerance. ... More
Motor Function Deficits Following Chronic Prenatal Ethanol Exposure are Linked to Impairments in Insulin/IGF, Notch and Wnt Signaling in the Cerebellum.
AuthorsTong M, Ziplow J, Chen WC, Nguyen QG, Kim C, de la Monte SM,
Journal
PubMed ID25035811
Fetal alcohol spectrum disorder (FASD) is associated with deficits in cerebellar function that can persist through adolescence. Previous studies demonstrated striking inhibition of insulin and insulin-like growth factor (IGF) signaling in ethanol-exposed cerebella. We sought to determine if FASD-induced impairments in motor function were associated with deficits in insulin/IGF signaling ... More
Impaired insulin/IGF signaling in experimental alcohol-related myopathy.
AuthorsNguyen VA, Le T, Tong M, Silbermann E, Gundogan F, de la Monte SM,
JournalNutrients
PubMed ID23016132
Alcohol-related myopathy (Alc-M) is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in ... More
Ceramide-mediated insulin resistance and impairment of cognitive-motor functions.
Authorsde la Monte SM, Tong M, Nguyen V, Setshedi M, Longato L, Wands JR,
JournalJ Alzheimers Dis
PubMed ID20693650
Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis (NASH) are associated with cognitive impairment, brain insulin resistance, and neurodegeneration. Recent studies linked these effects to increased pro-ceramide gene expression in liver and increased ceramide levels in serum. Since ceramides are neurotoxic and cause insulin resistance, we directly examined the ... More
Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death.
AuthorsTejada T, Catanuto P, Ijaz A, Santos JV, Xia X, Sanchez P, Sanabria N, Lenz O, Elliot SJ, Fornoni A,
JournalKidney Int
PubMed ID18385666
Loss of podocytes by apoptosis characterizes the early stages of diabetic nephropathy. To examine its mechanism we studied glomeruli and podocytes isolated from db/db mice with early diabetic nephropathy and albuminuria. Phosphorylation of AKT (protein kinase B, a key survival protein) was found to be lower in the glomeruli of ... More
Imipramine blocks ethanol-induced ASMase activation, ceramide generation, and PP2A activation, and ameliorates hepatic steatosis in ethanol-fed mice.
AuthorsLiangpunsakul S, Rahmini Y, Ross RA, Zhao Z, Xu Y, Crabb DW
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID22194417
Our previous data showed the inhibitory effect of ethanol on AMP-activated protein kinase phosphorylation, which appears to be mediated, in part, through increased levels of hepatic ceramide and activation of protein phosphatase 2A (Liangpunsakul S, Sozio MS, Shin E, Zhao Z, Xu Y, Ross RA, Zeng Y, Crabb DW. Am ... More