scholarly journals Optimization of miR-22 expression cassette for rAAV delivery on diabetes

2022 ◽  
Vol 3 (1) ◽  
Author(s):  
Li Yang ◽  
Wenya Du ◽  
Zhaoyue Zheng ◽  
Li Wang ◽  
Lin Xiao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Rna Polymerase Iii ◽  
The Other ◽  
Diabetic Mice ◽  
High Fat ◽  
Egfp Gene ◽  
Adeno Associated Virus ◽  
Powerful Approach

AbstractMicroRNA-22 (miR-22) was suggested to be important for type 2 diabetes but its functions for this disease remained unclear. Recombinant adeno-associated virus (rAAV)-mediated miR delivery is a powerful approach to study miR functions in vivo, however, the overexpression of miR-22 by rAAV remains challenging because it is one of the most abundant miRs in the liver. In this study, a series of expression cassettes were designed and compared. It was shown that different lengths of primary miR-22 were overexpressed in HEK293 and HeLa cells but the longer ones were more efficiently expressed. miR-22 may be placed in either introns or the 3′ UTR of a transgene for efficient overexpression. RNA polymerase III or II promoters were successfully utilized for miR expression but the latter showed higher expression levels in cell lines. Specifically, miR-22 was expressed efficiently together with an EGFP gene. After screening, a liver-specific TTR promoter was chosen to overexpress miR-22 in diabetic mice fed a high-fat diet. It was shown that miR-22 was overexpressed 2-3 folds which improved the insulin sensitivity significantly. The approach utilized in this study to optimize miR overexpression is a powerful tool for the creation of efficient rAAV vectors for the other miRs.

Hypoglycemic effects of Auricularia auricula polysaccharides on high fat diet and streptozotocin-induced diabetic mice using metabolomics analysis

2021 ◽  
Author(s):  
nannan liu ◽  
Xuefeng Chen ◽  
Juanna Song ◽  
Mengyin Chen ◽  
Pin Gong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
Male Mice ◽  
High Fat ◽  
Auricularia Auricula ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Metabolomic Approach ◽  
Metabolomics Analysis

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...

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

2022 ◽  
Author(s):  
Somayeh Aslani ◽  
Saman Bahrambeigi ◽  
Davoud Sanajou
Keyword(s):  
Liver Injury ◽  
High Fat Diet ◽  
Lifestyle Modification ◽  
Serum Levels ◽  
Diabetic Mice ◽  
High Fat ◽  
Lifestyle Modifications ◽  
Gamma Glutamyl Transpeptidase ◽  
Alcoholic Fatty Liver

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.

scholarly journals Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 159 ◽  
Author(s):  
Kyung-Ah Park ◽  
Zhen Jin ◽  
Jong Youl Lee ◽  
Hyeong Seok An ◽  
Eun Bee Choi ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Fusion Protein ◽  
High Fat Diet ◽  
Memory Deficits ◽  
Receptor Expression ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

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.

scholarly journals Beneficial Effects of Potentilla discolor Bunge Water Extract on Inflammatory Cytokines Release and Gut Microbiota in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 670 ◽  
Author(s):  
Lihua Han ◽  
Tiange Li ◽  
Min Du ◽  
Rui Chang ◽  
Biyuan Zhan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Intestinal Inflammation ◽  
Water Extract ◽  
Perennial Herb ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

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.

scholarly journals In vivo antidiabetic activities of green and black tea polysaccharides using streptozotocin- induced diabetic mice fed with a high-fat diet

2019 ◽  
Vol 8 ◽  
Author(s):  
Kübra Akalın ◽  
Arzu Taş Ekiz ◽  
Fatih Karakaya ◽  
Ayse Karadag ◽  
Ebru Pelvan ◽  
...  
Keyword(s):  
Body Weight ◽  
Treatment Period ◽  
High Fat Diet ◽  
Black Tea ◽  
High Energy ◽  
Diabetic Mice ◽  
High Fat ◽  
Tea Polysaccharides ◽  
Green And Black Tea

Type-2 diabetes (T2D) is the most common type of chronic disease in adults and accounts for around 90% of all cases of diabetes. Therefore, developing dietary supplements from natural sources, such as teas, is of great interest. Seven diet groups together with a parallel control group were used for three periods of 16 weeks in total [stabilization period (W-2-W0), model period (W0-W8), and treatment period (W8-W14)]. The primary aim of this study was to investigate the in vivo antidiabetic activities of green and black tea polysaccharides (GTPS and BTPS, respectively) using streptozotocin induced diabetic mice fed with either a high-fat diet (HFD) or normal diet (ND). Streptozotocin and HFD induced T2D in vivo model was developed during the model period (W0-W8) in C57BL/6J male mice. Both GTPS and BTPS groups were administrated for 6 weeks (daily 400 mg/kg body weight) by oral gavage throughout the treatment period (W8-W14). The results showed that BTPS group significantly (P < 0.05) decreased the fasting blood glucose level in diabetic mice even fed with a HFD and improved the insulin resistance. Similar effect was not obtained when GTPS group fed with a HFD. In addition, BTPS group fed with a HFD effectively suppressed the body weight gain despite high energy intake and was more successful than its GTPS counterpart group in healing pathologies of liver and affected plasma blood lipid levels due to streptozotocin and HFD-induced diabetes. The present work suggests that BTPS can be used as an antidiabetic dietary supplement without posing any potential health risk.

Antidiabetic Effect of Sargassum wightii and Ulva fasciata in High Fat Diet and Multi Low Dose Streptozotocin Induced Type 2 Diabetic Mice

2016 ◽  
Vol 4 (2) ◽  
pp. 13 ◽  
Author(s):  
Lucy Mohapatra ◽  
Subrat Kumar Bhattamishra ◽  
Ramachandra Panigrahy ◽  
Sambit Parida ◽  
Premalata Pati
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Mice ◽  
High Fat ◽  
Antidiabetic Effect ◽  
Ulva Fasciata ◽  
Sargassum Wightii ◽  
Type 2 Diabetic

scholarly journals TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet fed mouse

2018 ◽  
Vol 132 (1) ◽  
pp. 69-83 ◽  
Author(s):  
Stella Bernardi ◽  
Barbara Toffoli ◽  
Veronica Tisato ◽  
Fleur Bossi ◽  
Stefania Biffi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
High Fat Diet ◽  
Disease Onset ◽  
High Fat ◽  
Primary Hepatocytes

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. The present study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD). After 4 weeks of HFD, mice were further randomized to receive either placebo or TRAIL, which was delivered weekly for 8 weeks. Body weight, food intake, fasting glucose, and insulin were measured at baseline and every 4 weeks. Tolerance tests were performed before drug randomization and at the end of the study. Tissues were collected for further analyses. Parallel in vitro studies were conducted on HepG2 cells and mouse primary hepatocytes. TRAIL significantly reduced body weight, adipocyte hypertrophy, free fatty acid levels, and inflammation. Moreover, it significantly improved impaired glucose tolerance, and ameliorated non-alcoholic fatty liver disease (NAFLD). TRAIL treatment reduced liver fat content by 47% in vivo as well as by 45% in HepG2 cells and by 39% in primary hepatocytes. This was associated with a significant increase in liver peroxisome proliferator-activated receptor (PPAR) γ (PPARγ) co-activator-1 α (PGC-1α) expression both in vivo and in vitro, pointing to a direct protective effect of TRAIL on the liver. The present study confirms the ability of TRAIL to significantly attenuate diet-induced metabolic abnormalities, and it shows for the first time that TRAIL is effective also when administered after disease onset. In addition, our data shed light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD.

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