The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats

Wang, Yan; Sun, Pei; Jin, Xia; Zhang, Chunxue; Pang, Shuguang

doi:10.1507/endocrj.ej16-0391

Cited by 15 publications

(14 citation statements)

References 29 publications

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“…However, in our study, the DM subjects were treated with insulin, insulin secretagogues and/or insulin sensitizers whose mechanisms of action are different. Wang et al revealed that FGF19 serum decreased in DM rats and was continuously reduced after metformin treatment via AMPK-FXR crosstalk [26]. However, Sonne et al showed no differences in FGF19 level in metformin-treated patients vs. patients treated with sulfonylureas and diet only [27].…”

Section: Discussionmentioning

confidence: 99%

Serum fibroblast growth factor 19 and endogenous islet beta cell function in type 2 diabetic patients

Tang

et al. 2019

Diabetol Metab Syndr

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Background Fibroblast growth factor 19 (FGF19) takes part in maintaining the balance of glycolipids and may be involved in regulating the secretory activity of islet beta cells in patients with type 2 diabetes. This study aimed to evaluate the relationship between the levels of serum FGF19 and endogenous islet beta cell function in type 2 diabetic patients. Methods Samples were obtained from 271 subjects: 85 drug-naïve type 2 diabetes participants exclusively on lifestyle intervention (N-DM group), 122 type 2 diabetes subjects previously used medications (DM group) and 64 normal controls (NC group). Serum FGF19 concentrations were measured by ELISA. The insulin sensitivity (MI), insulin secretion (AUCins/AUCglu) and insulin secretion-sensitivity index-2 (ISSI-2) were also measured in the N-DM and DM. Results Serum FGF19 levels decreased, in order, from the NC group [median (interquartile range), 245.03 (126.23–317.43) pg/mL] to the N-DM group [170.05 (89.01–244.70) pg/mL] and, finally, to the DM group [142.25 (55.55–187.58) pg/mL] (p for trend < 0.05). Among subjects in the DM group, there was a positive trend in the serum FGF19 concentration; plasma insulin levels at 60 min, 120 min (INS60, INS120, respectively); and area under the insulin curve (AUCins) at two points (r = 0.214, p = 0.025; r = 0.189, p = 0.048; r = 0.188, p = 0.049). However, the differences were no longer observed among the N-DM subjects. Simultaneously, the ISSI-2 was closely related to the serum FGF19 levels (r = 0.297, p = 0.002) among DM subjects. Furthermore, after adjusting for age, sex, duration, therapy and other clinical factors via multiple logistic regression analysis, ISSI-2 was a key independent factor in the levels of FGF19 (β = 0.281, t = 2.557, p = 0.013). Conclusions The serum FGF19 level has a close relation with endogenous beta cell function among DM subjects, as assessed by the ISSI-2. As ISSI-2 is higher in N-DM group, FGF19 may be a main protector in dysfunction of beta cell.

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Section: Discussionmentioning

confidence: 99%

Serum fibroblast growth factor 19 and endogenous islet beta cell function in type 2 diabetic patients

Tang

et al. 2019

Diabetol Metab Syndr

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“…In the research, we established a rat model with T2DM by HFD and small-dose STZ injection. It is reported that HFD causes insulin resistance, STZ is toxic to islet β cells, and injection of large doses of STZ can damage most islet β cells to induce T1DM, while our laboratory demonstrated that low-dose STZ can be used to prepare T2DM models [14, 15].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism may be that activation of FXR increases glycogen synthesis and reduces glycolysis. In addition, FXR protects islet beta cell activity and affects glucose regulation [15]. In the liver, FXR activation induces SHP and leads to a decrease in CYP7A1 activity.…”

Section: Discussionmentioning

confidence: 99%

A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

et al. 2019

International Journal of Endocrinology

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Background Type 2 diabetes has become one of the most common diseases worldwide, causing a serious social burden. As a first-line treatment for diabetes, metformin can effectively improve insulin resistance. It has been reported that 12α-hydroxylated BA (mainly CA) is associated with insulin resistance. The purpose of this study was to analyze the changes in CA and possible signaling mechanisms in diabetic rats after metformin intervention. Methods HepG2 cells were cultured after adding different concentrations of metformin. The cell viability was measured using CCK8 kit, and the expression of FXR, MAFG, and CYP8B1 in cells was detected by WB. The rat models of type 2 diabetes were induced by low-dose streptozotocin by feeding a high-fat diet, and the control rats (CON) were fed on normal food; the diabetic rats (DM) were given a high-fat diet without supplementation with metformin, while the metformin-treated diabetic rats (DM + MET) were given a high-fat diet and supplemented with metformin. Biochemical parameters were detected at the end of the test. Expression levels of FXR, CYP8B1, and MAFG were assessed by WB. Serum CA were measured using an enzyme-linked immunosorbent assay (ELISA). Results In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1. Metformin-treated DM rats showed improved glucose and bile acid metabolism. In addition, significantly increased FXR and MAFG and decreased CYP8B1 were observed in DM + MET rats. At the same time, the CA content of metformin-treated rats was lower than that of diabetic rats. Conclusion Changes in CA synthesis after metformin treatment may be associated with inhibition of CYP8B1. These results may play an important role in improving insulin sensitivity after metformin treatment.

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“…The levels of fasting blood glucose and body weight were monitored every week. Diabetes was regarded as successfully induced in rats with fasted blood glucose levels of >11 mmol/L that persisted for more than 4 weeks (Wang et al, 2017b ).…”

Section: Methodsmentioning

confidence: 99%

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

et al. 2017

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Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats.Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis.Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density.Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair.

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The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats

Cited by 15 publications

References 29 publications

Serum fibroblast growth factor 19 and endogenous islet beta cell function in type 2 diabetic patients

Serum fibroblast growth factor 19 and endogenous islet beta cell function in type 2 diabetic patients

A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

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