Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 Diabetic db/db Mice

Kim, Young-Je; Jung, Un Ju

doi:10.3390/ijms20092303

Cited by 19 publications

(10 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, under the condition of long-term exposure to high blood glucose levels, the HbAlc level significantly increases, which leads to vascular endothelial injury and vascular dysfunction, and is the basis of diabetic vascular complications. Therefore, HbA1c is a simple and reliable marker for testing insulin sensitivity in diabetic patients, and the optimum level of HbA1c is 5.6–7% in patients with T2DM ( Kim and Jung, 2019 ). In diabetic db/db mice, AOS improves hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells

et al. 2021

View full text Add to dashboard Cite

We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In contrast, consistent with previous reports 29 , we found that Pg-treatment further reduced glycogen storage in the liver of db/db mice indicating that glucose incorporation into glycogen was further decreased by the PG-treatment in the diabetic mice. However, it should be noted that such changes in hepatic glucose metabolites could also be induced by hepatic enzyme activities due to increased plasma insulin-counter regulatory hormone levels 30,31 , which were not extensively measured in the present study.…”

Section: Discussionmentioning

confidence: 74%

Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

Kashiwagi

Aburaya

Sugiyama

et al. 2021

Preprint

View full text Add to dashboard Cite

Periodontal infection is thought to generate systemic inflammation, thus aggravating diabetes. Furthermore, orally administered periodontal pathogens may directly alter the gut microbiota. To elucidate this, using an obese db/db diabetes mice, orally treated with Porphyromonas gingivalis (Pg), we screened for Pg-specific peptides in intestinal fecal specimens and examined whether Pg localization affected the intestinal microbiota profile altering gut metabolite levels. Finally, we screened whether deterioration of fasting hyperglycemia was related to changes in intrahepatic glucose metabolism, using proteome and metabolome analyses. As results; (1) Oral Pg treatment aggravated both fasting and postprandial hyperglycemia (P < 0.05) with a significant (P < 0.01) increase in dental alveolar bone resorption. (2) Pg-specific peptides were identified in fecal specimens after oral Pg treatment and intestinal Pg profoundly altered gut microbiome profiles at the phylum, family, and genus levels. Prevotella showed the largest increase in abundance. Furthermore, Pg-treatment significantly altered intestinal metabolite levels. (3) Fasting hyperglycemia was associated with increases in gluconeogenesis-related enzyme and metabolite levels without changes in proinflammatory cytokine expressions and insulin resistance. This work reveals that oral Pg administration induced gut microbiota changes, leading to entero-hepatic metabolic derangements, thereby aggravating hyperglycemia in an obese type 2 diabetes mouse model.

show abstract

“…T2DM patients have an abnormal blood lipid profile. Increased serum AST and ALT levels are associated with IR [51,52]. In addition, plasma levels of TG, TC, and LDL were significantly higher than those of normal subjects [53].…”

Section: Discussionmentioning

confidence: 91%

Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 Ameliorates Insulin Resistance in Palmitic Acid-Induced HepG2 Cells and High Fat Diet-Induced Mice

et al. 2021

View full text Add to dashboard Cite

The purpose of this study was to evaluate the capacity of Lactiplantibacillus plantarum MG4296 (MG4296) and Lacticaseibacillus paracasei MG5012 (MG5012) on insulin resistance (IR) and diabetes-related metabolic changes in palmitic acid (PA)-induced HepG2 cells and high-fat diet-induced mice. In vitro, cell-free extracts of MG4296 and MG5012 alleviated IR by increasing glucose uptake and glycogen content in PA-induced insulin-resistant HepG2 cells. In vivo, MG4296 and MG5012 supplementation markedly decreased body weight and glucose tolerance. Administration of both strains also improved serum glucose, glycated hemoglobin, insulin, triglyceride, LDL/HDL ratio, and homeostatic model assessment of IR (HOMA-IR). Histopathological analysis of liver tissue demonstrated a significant reduction in lipid accumulation and glycogen content. Moreover, MG4296 and MG5012 treatment enhanced phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt) expression in the liver. Overall, MG4296 and MG5012 could prevent HFD-induced glucose tolerance and hyperglycemia by improving IR. Therefore, L. plantarum MG4296 and L. paracasei MG5012 could be useful as new probiotics candidates to improve T2DM.

show abstract

Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 Diabetic db/db Mice

Cited by 19 publications

References 66 publications

Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells

Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells

Porphyromonas gingivalis induces entero-hepatic metabolic derangements with alteration of gut microbiota in a type 2 diabetes mouse model

Lactiplantibacillus plantarum MG4296 and Lacticaseibacillus paracasei MG5012 Ameliorates Insulin Resistance in Palmitic Acid-Induced HepG2 Cells and High Fat Diet-Induced Mice

Contact Info

Product

Resources

About