scholarly journals Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Hong-Xin Cui ◽  
Ya-Nan Hu ◽  
Jing-Wan Li ◽  
Ke Yuan

Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.

2018 ◽  
Author(s):  
Isaacson Adelani ◽  
Esther Bankole ◽  
Oluwakemi Rotimi ◽  
Solomon Rotimi

Redox Biology ◽  
2016 ◽  
Vol 8 ◽  
pp. 199-204 ◽  
Author(s):  
Derya Selcen Salmanoglu ◽  
Tugba Gurpinar ◽  
Kamil Vural ◽  
Nuran Ekerbicer ◽  
Ertan Darıverenli ◽  
...  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebekah Lambert ◽  
Sarah Srodulski ◽  
Xiaoli Peng ◽  
Kenneth B Margulies ◽  
Florin Despa ◽  
...  

Intracellular Na + concentration ([Na + ] i ) is a key regulator of cardiac Ca 2+ cycling, contractility and metabolism. [Na + ] i is elevated in myocytes from failing hearts, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na + ] i is also increased in type-2 diabetes (T2D) due to enhanced activity of the Na + -glucose cotransporter (SGLT). To test this hypothesis, we used myocardial tissue from humans with T2D and an animal model of late-onset T2D (HIP rats). We found increased SGLT expression in failing hearts from patients with T2D compared to non-diabetic individuals (by 55±16%) and in HIP rat hearts ( vs . age-matched wild-type, WT, littermates; by 59±17%). [Na + ] i , measured with the fluorescent indicator SBFI, is increased in myocytes from diabetic HIP rats, both at rest (14.7±0.9 mM compared to 11.4±0.7 mM in WT) and during electrical stimulation at 2 Hz (17.3±0.8 mM vs . 15.0±0.7 mM in WT). However, the Na + /K + -pump function (measured as the rate of pump-mediated [Na + ] i decline in intact myocytes) is not significantly altered in diabetic HIP rats. This result suggests that higher [Na + ] i is due to an increased Na + entry in HIP rat myocytes. Indeed, Na + influx, assessed as the rate of [Na + ] i rise upon Na + /K + -pump inhibition with 10 mM ouabain, was significantly larger in myocytes from diabetic HIP vs . WT rats (1.74±0.13 mM/min vs . 1.27±0.07 mM/min). SGLT inhibition with 250 μM phlorizin significantly reduced Na + influx in myocytes from diabetic HIP rats (to 1.08±0.20 mM/min), while it had no effect in the WT (1.14±0.21 mM/min). Phlorizin also significantly decreased glucose uptake in HIP rat myocytes (by 50±10 %) but not in WT, indicating an increased reliance on SGLT for glucose uptake in T2D hearts. In agreement with this result, the insulin-sensitive glucose uptake was greatly reduced in HIP rat myocytes vs . WT. These data suggest that SGLT is upregulated in diabetic hearts to compensate for reduced insulin-mediated glucose uptake. In summary, we found that [Na + ] i is elevated in myocytes from diabetic HIP rats due to an increased Na + entry via the Na + -glucose cotransporter. Higher [Na + ] i may contribute to arrhythmogenesis and oxidative stress in diabetic hearts.


PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68217 ◽  
Author(s):  
Emilie Vessières ◽  
Anne-Laure Guihot ◽  
Bertrand Toutain ◽  
Maud Maquigneau ◽  
Céline Fassot ◽  
...  

2011 ◽  
Vol 106 (5) ◽  
pp. 648-655 ◽  
Author(s):  
Jiejie Hao ◽  
Weili Shen ◽  
Lijuan Sun ◽  
Jiangang Long ◽  
Edward Sharman ◽  
...  

Treatment with a combination of four nutrients, i.e. R-α-lipoic acid, acetyl-l-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto–Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.


2020 ◽  
Vol 17 (6) ◽  
pp. 147916412096699
Author(s):  
Wenru Li ◽  
Chaonan Zhu ◽  
Tianheng Liu ◽  
Weifang Zhang ◽  
Xu Liu ◽  
...  

Aims: The objective of this study was to explore the effects of epigallocatechin-3-gallate (EGCG) on type 2 diabetes mellitus (T2DM). Main methods: Male Sprague–Dawley rats were allocated into six groups. The control group received a conventional diet. The diabetic group received a high-sucrose high-fat (HSHF) diet for 4 weeks and then was fasted and injected with streptozotocin (STZ); subsequently, the rats received a HSHF diet for another 4 weeks to develop diabetes. The four treatment groups were diabetic rats that received intragastric metformin (500 mg/kg/day) or EGCG (25, 50, and 100 mg/kg/day) for 10 weeks. All groups except the control group received a HSHF diet throughout the experiment. Several biochemical parameters such as fasting blood glucose (FBG), postprandial blood glucose (PBG), liver glycogen, muscle glycogen, fasting serum insulin (FSI), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess the effects of EGCG on glycemic control, insulin resistance, lipid profile, and oxidative stress. Furthermore, oxidative stress in pancreatic islet β cells was detected by dihydroethidium staining. Key findings: A HSHF diet and STZ injection induced T2DM, as indicated by changed blood glucose and body weight, which was accompanied by insulin resistance, an altered lipid profile, and oxidative stress. Interestingly, EGCG treatment dose-dependently recovered these indexes. Significance: EGCG successfully ameliorated glycemic control and insulin sensitivity while reducing the lipid profile and oxidative stress in a T2DM rat model.


2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.


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