Long-acting hypoglycemic effects of PEGylated FGF21 and insulin glargine in mice with type 1 diabetes

Xu, Pengfei; Ye, Xianlong; Zhang, Yingjie; Yuan, Qingyan; Liu, Mingyao; Wu, Qiang; Ren, Guangxin; Li, Deshan

doi:10.1016/j.jdiacomp.2014.10.001

Cited by 25 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study on heap 1-6 cells indicated that the treatment with 100nM insulin significantly down regulated the expression of G6Pase and PEPCK . However, Xu et al (2015) suggested that insulin glargine (a long-acting insulin analogue) had no effect on G6Pase or PEPCK. In extremely low birth weight infants receiving total parenteral nutrition, insulin is not able to regulate gluconeogenesis, indicating that insulin has no effect on PEPCK or G6Pase (Chacko et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

Xiong

Song

Han

et al. 2016

Rev. Bras. Cienc. Avic.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…Interestingly, Ziv et al (1996) showed that insulin failed to inhibit PEPCK and G6Pase activity even during the pre-diabetic (A) state. Recent data also suggest that insulin glargine (a long-acting insulin analogue) has no effect on G6Pase or PEPCK (Xu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

Xiong

Song

Han

et al. 2016

Rev. Bras. Cienc. Avic.

View full text Add to dashboard Cite

“…Xu et al. also found that PEGylated FGF21 can alleviate hyperglycemia in T1DM by accelerating glycolysis and inhibiting hepatic gluconeogenesis . Although PEGylation can extend the circulating half‐life of many pharmaceutical proteins, it carries the risk of vacuole formation; in which accumulation of vacuoles in renal tubular epithelium is a particular safety concern in diabetic patients with renal failure.…”

Section: Use Of Fgf21 Analogs In the Manipulation Of Diabetesmentioning

confidence: 99%

“…161 Xu et al also found that PEGylated FGF21 can alleviate hyperglycemia in T1DM by accelerating glycolysis and inhibiting hepatic gluconeogenesis. 162 Although PEGylation can extend the circulating halflife of many pharmaceutical proteins, it carries the risk of vacuole formation 163,164 ; in which accumulation of vacuoles in renal tubular epithelium is a particular safety concern in diabetic patients with renal failure. Therefore, Xu et al have explored a structure-based engineering approach to identify the optimized PEG attachment site and PEG configuration in order to minimize the vacuole formation.…”

Section: Pegylated Fgf21mentioning

confidence: 99%

Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus

Leung

2016

Medicinal Research Reviews

View full text Add to dashboard Cite

Fibroblast growth factor (FGF) 21 is a distinctive member of the FGF family that functions as an endocrine factor. It is expressed predominantly in the liver, but is also found in adipose tissue and the pancreas. Pharmacological studies have shown that FGF21 normalizes glucose and lipid homeostasis, thereby preventing the development of metabolic disorders, such as obesity and diabetes. Despite growing evidence for the therapeutic potential of FGF21, paradoxical increases of FGF21 in different disease conditions point to the existence of FGF21 resistance. In this review, we give a critical appraisal of recent advances in the understanding of the regulation of FGF21 production under various physiological conditions, its antidiabetic actions, and the clinical implications. We also discuss recent preclinical and clinical trials using engineered FGF21 analogs in the management of diabetes, as well as the potential side effects of FGF21 therapy.

show abstract

“…When the OD600 reach 0.4 to 0.6, FGF21 protein expressed at 25℃ for 6 hours (IPTG final concentration: 0.25mmol/L). The FGF21 was purified by AKTA Purifier (GE Healthcare) [22]. The activity assay of FGF21 in vitro performed by HepG2 cells cultured as a materials of glucose uptake in a 96-well plate and incubated at 37℃ in a 5% CO 2 humidified atmosphere.…”

Section: Preparation Of Fgf21mentioning

confidence: 99%

FGF21 Attenuates Neurodegeneration though Modulating Neuroinflammation and Oxidant-stress

Kang

Wang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background It is reported that FGF21 can repair nerve injury, but the specific mechanism is less studied. The present study was designed to investigate the effects of FGF21 on neurodegeneration and possible mechanisms of the aging and diabetic mice, which were susceptible to Alzheimer's disease (AD). Methods The diabetic mice and aging mice were used to study the effects of FGF21 on neurodegeneration and possible mechanisms. These mice were administrated with PBS, FGF21 or metformin once daily for 4 or 6 months. Then the mechanism was verified in SH-SY5Y cells. The relative gene expressions for neurodegeneration were assessed by Quantitative Real Time-PCR, Western blot and others. Results FGF21 inhibited the loss of nerve cells and intracellular edema around hippocampus in diabetic mice and aging mice. In vivo results revealed that administration of FGF21 led to suppress the aggregation of Tau and β-Amyloid 1-42 , which resulted in apoptosis in nerve cells. Meanwhile, FGF21 significantly reduced the expression of NF-κB, IL6 and IL8 (p<0.05) and enhanced anti-oxidant enzymes (p<0.05) in diabetic mice. In addition, the phosphorylation of AKT and AMPKα was increased by FGF21 treated in diabetic mice, which were considered as anti-inflammation and anti-oxidant stress pathway. The relative gene expressions of neurodegeneration were also demonstrated in aging mice, which showed similar trends with diabetic mice. In vitro experiment showed that the aggregation of Tau and β-Amyloid 1-42 was increased by LPS in SH-SY5Y cells, and FGF21 inhibited the aggregation. Conclusion As shown above, FGF21 attenuated neurodegeneration by reducing neuroinflammation and oxidant stress though regulating the NF-κB pathway and AMPKα/AKT pathway, which enhanced the protective effect on mitochondria in nerve cells. Key words : FGF21, diabetes, neurodegeneration, inflammation, oxidant stress.

show abstract

Long-acting hypoglycemic effects of PEGylated FGF21 and insulin glargine in mice with type 1 diabetes

Cited by 25 publications

References 27 publications

Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus

FGF21 Attenuates Neurodegeneration though Modulating Neuroinflammation and Oxidant-stress

Contact Info

Product

Resources

About