Effects of Oral Antidiabetic Drugs on Changes in the Liver-to-Spleen Ratio on Computed Tomography and Inflammatory Biomarkers in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Yabiku, Koichi; Mutoh, Akiko; Miyagi, Kazufumi; Takasu, Nobuyuki

doi:10.1016/j.clinthera.2017.01.015

Cited by 21 publications

(34 citation statements)

References 30 publications

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“…Metformin was previously used to treat liver injury induced by endotoxin in rats after partial hepatectomy (La Mura et al, 2013) and also treated NAFLD (Yabiku et al, 2017). These reports are in agreement with our results that showed effective protection of hepatocytes with metformin ( Figs.…”

Section: Discussionsupporting

confidence: 92%

Metformin Protects Against Thioacetamide Induced Liver injury in Rats

et al. 2018

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Potent heptatotoxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are used to evaluate hepatoprotective agents. Here we sought to investigate the potential protective effect of the antidiabetic and antioxidant drug, metformin against liver injury induced by TAA. Model group rats received several injections of TAA (200 mg/kg) before being sacrificed after 10 weeks and the protective group started the treatment two weeks prior to TAA injections and continued receiving both agents, metformin and TAA until the end of the experiment, week 10. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for oxidative and anti-oxidative stress markers that are known to be modulated in liver injury. Profound damage in the hepatic tissue of the model group such as liver fibrosis and destruction of hepatic architectures were revealed, which were protected by metformin comparable to the control group. TAA augmented the oxidative stress biomarker, malondialdehyde (MDA) and ameliorated the antioxidant superoxide dismutase (SOD), which were significantly (p<0.05) protected by metformin treatment. These results indicate that metformin effectively protects against TAA-induced hepatotoxicity in a rat model.

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Section: Discussionsupporting

confidence: 92%

Metformin Protects Against Thioacetamide Induced Liver injury in Rats

et al. 2018

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“…Others have failed to see any decrease in plasma aminotransferases or IHTG. 137,[166][167][168][169] Of note, in all 3 controlled studies treatment with sitagliptin resulted in negative findings. 137,167,168 Taken together, while a number of mechanisms have been proposed for DPP-IV inhibitors in animal models of NASH, 98,170 strong clinical evidence for their clinical use in NAFLD/NASH is still lacking.…”

Section: Lactate Amino Acidsmentioning

confidence: 99%

From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options

2019

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The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to have reached 25% or more in adults. NAFLD is prevalent in obese individuals, but may also affect nonobese insulin-resistant individuals. NAFLD is associated with a 2-to 3-fold increased risk of developing type 2 diabetes (T2D), which may be higher in patients with more severe liver diseasefibrosis increases this risk. In NAFLD, not only the close association with obesity, but also the impairment of many metabolic pathways, including decreased hepatic insulin sensitivity and insulin secretion, increase the risk of developing T2D and related comorbidities. Conversely, patients with diabetes have a higher prevalence of steatohepatitis, liver fibrosis and end-stage liver disease. Genetics and mechanisms involving dysfunctional adipose tissue, lipotoxicity and glucotoxicity appear to play a role. In this review, we discuss the altered pathophysiological mechanisms that underlie the development of T2D in NAFLD and vice versa. Although there is no approved therapy for the treatment of NASH, we discuss pharmacological agents currently available to treat T2D that could potentially be useful for the management of NASH.

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“…36 The role of metformin on the nonalcoholic fatty liver disease without glucose intolerance or diabetes is not accepted commonly by most researchers. 37…”

Section: Discussionmentioning

confidence: 99%