A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major complication linked with the metabolic syndrome associated with dyslipidemia, inflammation, and oxidative stress. Impact of type 2 diabetes with hyperlipidemia in NAFLD has to be established, as well as the utility of commonly prescribed anti-diabetic and lipid-lowering agents in improving liver injury markers. Genetic type 2 diabetic Goto-Kakizaki rats were fed with a high-fat diet to test hepatic effects of type 2 diabetes with hyperlipidemia and the effect of atorvastatin and insulin, individually and in combination, in systemic and hepatic inflammatory and oxidative stress markers. High-fat diet aggravated fasting glycemia, systemic and liver lipids, and inflammatory and oxidative stress markers. Individual treatments improved glycemic and lipid profiles, but failed to improve inflammatory markers, whereas insulin was able to reduce liver oxidative stress parameters. Combination of insulin and atorvastatin further improved glycemic and lipid profiles and decreased circulating C-reactive protein levels and liver inflammatory and oxidative stress markers. Insulin and atorvastatin combination leads to better glycaemic and lipid profiles and to better protection against liver inflammation and oxidative stress, giving a superior level of liver protection in type 2 diabetic with hyperlipidemia.

Diabetes and Nonalcoholic Fatty Liver Disease: A Pathogenic Duo

“…Therefore, these models are unable to facilitate systematic examination of the effect of timed onset of diabetes added to a high-fat diet or to a metabolic syndrome phenotype; however, interventions targeting hyperglycemia in diabetes, for example, can be trialled in them. To date, these interventions are relatively few and include hepatic antisteatotic and systemic antiinflammatory effects of a selective dipeptidyl peptidase-IV (DPP-IV) inhibitor in a murine diabetes model (126), statin therapy with either metformin (127) or insulin (128) in db/db fat-fed mice, and peroxisome proliferator-activated receptor (PPAR)-␣ agonist treatment in the foz/foz cholesterol-fed model (129). This limited series of studies is collated in Table 2 and collectively implicates dyslipidemia, insulin resistance, and possibly hyperglycemia in effects of type 2 diabetes on NAFLD and its progression.…”

Methylglyoxal causes structural and functional alterations in adipose tissue independently of obesity

“…For carbonyl determinations, extracts were prepared as stated before (Matafome et al, 2009(Matafome et al, , 2011.Samples were derivatized with 10 mM 2, 4-dinitrophenylhydrazine (DNPH) in 10% trifluoroacetic acid (TFA) and the reaction was stopped with trichloroacetic acid (TCA). After centrifugation (14000×g, 5 minutes, 4°C) pellets were washed twice in ethyl acetate: ethanol 1:1 (v/v).…”

“…We have previously demonstrated hepatic inflammatory infiltration in models of hyperglycaemia and hyperlipidemia (Matafome et al, 2009(Matafome et al, , 2011. Several studies demonstrated that similar events occur in adipose tissue in models of diet-induced obesity and in obese individuals (Cancello et al, 2005;Lumeng et al, 2007;Olefsky & Glass, 2010;Pang et al, 2008).…”

Alkannin Inhibited Hepatic Inflammation in Diabetic Db/Db Mice

“…Diabetes mellitus causes dysregulation in carbohydrate, fat and protein metabolism, which may lead to serious complication, including blindness, renal failure, liver injury, nerve damage, and atherosclerosis [3, 4]. Diabetes-induced liver injury has received much attention, which has been illustrated from inflammatory responses, liver fibrosis and lipid accumulation [5, 6]. Among these responses, liver inflammation is a critical mechanism, and several studies have reported that anti-inflammation agents showed efficacy in reducing blood glucose level, enhanced insulin activity and protected diabetes caused by liver injury, and it may be a potential therapeutic target for this disease [7].…”