FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice

2022 ◽  
Author(s):  
Somayeh Aslani ◽  
Saman Bahrambeigi ◽  
Davoud Sanajou

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.

2021 ◽  
Author(s):  
nannan liu ◽  
Xuefeng Chen ◽  
Juanna Song ◽  
Mengyin Chen ◽  
Pin Gong ◽  
...  

This study evaluated the hypoglycemic effect of Auricularia auricula polysaccharides (AAPs) on streptozotocin-induced type 2 diabetes mellitus (T2DM) male mice (C57BL/6J) using a metabolomic approach based on ultrahigh-performance liquid chromatography–Q...


Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 159 ◽  
Author(s):  
Kyung-Ah Park ◽  
Zhen Jin ◽  
Jong Youl Lee ◽  
Hyeong Seok An ◽  
Eun Bee Choi ◽  
...  

Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.


Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 670 ◽  
Author(s):  
Lihua Han ◽  
Tiange Li ◽  
Min Du ◽  
Rui Chang ◽  
Biyuan Zhan ◽  
...  

Potentilla discolor Bunge (PDB), a perennial herb, has been used as a traditional Chinese medicine in the therapy of many diseases. The aim of the current study was to investigate the effect of PDB water extract on systemic inflammation and gut microbiota in type 2 diabetic (T2D) mice induced by high-fat diet (HFD) and streptozotocin (STZ) injection. C57BL/6J mice were randomly divided into a normal diet (ND) group, T2D group, and PDB group (diabetic mice treated with PDB water extract at a dose of 400 mg/kg body weight). Results showed that PDB significantly decreased the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines in serum. Further investigation showed that PDB significantly reduced the ratio of Firmicutes/Bacteroidetes and the relative abundance of Proteobacteria in fecal samples of diabetic mice. In addition, PDB notably alleviated intestinal inflammation as evidenced by decreased expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB), and inflammatory cytokines. PDB also reversed the decreased expression of intestinal mucosal tight junction proteins including Claudin3, ZO-1, and Occludin. Meanwhile, the levels of fecal acetic acid and butyric acid and their specific receptors including G-protein-coupled receptor (GPR) 41 and 43 expression in the colon were also increased after PDB treatment. Our results indicated that PDB might serve as a potential functional ingredient against diabetes and related inflammation.


Author(s):  
Christina T Saed ◽  
Amanda A Greenwell ◽  
Seyed Amirhossein Tabatabaei Dakhili ◽  
Keshav Gopal ◽  
Farah Eaton ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess fat in the liver in the absence of alcohol and increases one’s risk for both diabetes and cardiovascular disease (e.g. angina). We have shown that the second-line anti-anginal therapy, ranolazine, mitigates obesity-induced NAFLD, and our aim was to determine whether these actions of ranolazine also extend to NAFLD associated with type 2 diabetes (T2D). 8-week-old male C57BL/6J mice were fed either a low-fat diet or a high-fat diet for 15-weeks, with a single dose of streptozotocin (STZ; 75 mg/kg) administered in the high-fat diet fed mice at 4-weeks to induce experimental T2D. Mice were treated with either vehicle control or ranolazine during the final 7-weeks (50 mg/kg once daily). We assessed glycemia via monitoring glucose tolerance, insulin tolerance, and pyruvate tolerance, whereas hepatic steatosis was assessed via quantifying triacylglycerol content. We observed that ranolazine did not improve glycemia in mice with experimental T2D, while also having no impact on hepatic triacylglycerol content. Therefore, the salutary actions of ranolazine against NAFLD may be limited to obese individuals but not those who are obese with T2D.


2016 ◽  
Vol 4 (2) ◽  
pp. 13 ◽  
Author(s):  
Lucy Mohapatra ◽  
Subrat Kumar Bhattamishra ◽  
Ramachandra Panigrahy ◽  
Sambit Parida ◽  
Premalata Pati

2020 ◽  
Vol 11 (12) ◽  
pp. 10617-10634
Author(s):  
Dan Jin ◽  
Baiyu Zhang ◽  
Qiaoling Li ◽  
Jingjing Tu ◽  
Benhong Zhou

Type 2 diabetes has a series of metabolic aberrations accompanied by chronic hyperglycemia, along with various comorbidities.


2020 ◽  
Vol 21 (5) ◽  
pp. 1870
Author(s):  
Do Yeon Kim ◽  
Sang Ryong Kim ◽  
Un Ju Jung

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.


Biochimie ◽  
2020 ◽  
Vol 168 ◽  
pp. 41-52 ◽  
Author(s):  
Mayank Choubey ◽  
Ashutosh Ranjan ◽  
Puran S. Bora ◽  
Amitabh Krishna

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