Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects

Watanabe, Hiroshi; Miyahisa, Masako; Chikamatsu, Mayuko; Nishida, Kimiaki; Minayoshi, Yuki; Takano, Mei; Ichimizu, Shota; Kobashigawa, Yoshihiro; Morioka, Hiroshi; Maeda, Hitoshi; Maruyama, Toru

doi:10.1016/j.jconrel.2020.05.036

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…Fibroblast growth factor 21 (FGF21), an important endocrine factor regulating glucose and lipid metabolism (15)(16)(17), may be a potential factor associated with GDM prediction, as it was recently found that serum FGF21 increased after 24 gestational weeks in GDM patients (18)(19)(20). Studies showed that FGF21 reduces blood glucose and regulates blood lipids without causing hypoglycemia in obese or type 2 diabetes patients (21)(22)(23), and FGF21 increases insulin sensitivity and improves islet b cell secretion and proliferation (15,22,23). As a metabolic factor, FGF21 increases in type 2 diabetes and obesity patients (23,24), which might be a kind of compensation for insulin deficiency (25) and one study confirmed that serum FGF21 increased before type 2 diabetes was diagnosed in women (26).…”

Section: Introductionmentioning

confidence: 99%

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study

Wang

Yuan

et al. 2021

Front. Endocrinol.

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BackgroundAs an important endocrine hormone regulating glucose metabolism, fibroblast growth factor 21 (FGF21) is increased in individuals with gestational diabetes mellitus (GDM) after 24 gestational weeks. However, it is unknown whether the increase in FGF21 precedes the diagnosis of GDM.MethodsIn this nested case-control study, 133 pregnant women with GDM and 133 pregnant women with normal glucose tolerance (NGT) were identified through propensity score matching, and serum FGF21 levels were measured at 14 to 21 gestational weeks, before GDM is routinely identified. The differences in FGF21 levels were compared. The association between FGF21 and the occurrence of GDM was evaluated using logistic regression models with adjustment for confounders.ResultsThe serum FGF21 levels of the GDM group at 14 to 21 gestational weeks were significantly higher than those of the NGT group overall (P < 0.001), with similar results observed between the corresponding BMI subgroups (P < 0.05). The 2nd (OR 1.224, 95% CI 0.603–2.485), 3rd (OR 2.478, 1.229–5.000), and 4th (OR 3.419, 95% CI 1.626–7.188) FGF21 quartiles were associated with greater odds of GDM occurrence than the 1st quartile after multivariable adjustments.ConclusionsThe serum FGF21 levels in GDM groups increased in the early second trimester, regardless of whether participants were stratified according to BMI. After adjusting for confounding factors, the FGF21 levels in the highest quartile were associated with more than three times higher probability of the diagnosis of GDM in the pregnancy as compared to levels in the first quartile.

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Section: Introductionmentioning

confidence: 99%

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study

Wang

Yuan

et al. 2021

Front. Endocrinol.

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“…2012 ) and has been reported to be safe and effective in clinical studies ( Geng et al. 2020 ; Watanabe et al. 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 21 exerts a protective effect on diabetes-induced cognitive decline by remodeling cerebral glucose and neurotransmitter metabolism in mice

Zhang,

Zheng,

et al. 2024

Cerebral Cortex

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Diabetes mellitus (DM) causes damage to the central nervous system, resulting in cognitive impairment. Fibroblast growth factor 21 (FGF21) exhibits the potential to alleviate neurodegeneration. However, the therapeutic effect of intracerebroventricular (i.c.v) FGF21 infusion on diabetes-induced cognitive decline (DICD) and its potential mechanisms remain unclear. In this study, the impact of FGF21 on DICD was explored, and 1H nuclear magnetic resonance (NMR)-based metabolomics plus 13C NMR spectroscopy in combine with intravenous [1-13C]-glucose infusion were used to investigate the underlying metabolic mechanism. Results revealed that i.c.v FGF21 infusion effectively improved learning and memory performance of DICD mice; neuron loss and apoptosis in hippocampus and cortex were significantly blocked, suggesting a potential neuroprotective role of FGF21 in DICD. Metabolomics results revealed that FGF21 modulated DICD metabolic alterations related to glucose and neurotransmitter metabolism, which are characterized by distinct recovered enrichment of [3-13C]-lactate, [3-13C]-aspartate, [4-13C]-glutamine, [3-13C]-glutamine, [4-13C]-glutamate, and [4-13C]- γ-aminobutyric acid (GABA) from [1-13C]-glucose. Moreover, diabetes-induced neuron injury and metabolic dysfunctions might be mediated by PI3K/AKT/GSK-3β signaling pathway inactivation in the hippocampus and cortex, which were activated by i.c.v injection of FGF21. These findings indicate that i.c.v FGF21 infusion exerts its neuroprotective effect on DICD by remodeling cerebral glucose and neurotransmitter metabolism by activating the PI3K/AKT/GSK-3β signaling pathway.

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“…By constructing a stable mutant FGF21 (mFGF21) and then genetically fusing it with human albumin through a polypeptide to form HSA-mFGF21, whose half-life is 20 times higher than that of FGF21. It can enter the body to play a continuous inhibitory effect on blood glucose, which is expected to become a new biological therapy for metabolic disorders including diabetes (Watanabe et al, 2020). In addition, the FGF21 analog LY2405319 (LY) with the half-life improving exerts an inhibitory effect on blood sugar and lipids, which indicates that the FGF21 pathway may be an ideal candidate for the treatment of metabolic diseases (Adams et al, 2013).…”

Section: Fibroblast Growth Factor 21 As a Potential Therapeutic Targetmentioning

confidence: 99%

Regulation and Potential Biological Role of Fibroblast Growth Factor 21 in Chronic Kidney Disease

2021

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Chronic kidney disease (CKD) is an incurable progressive disease with the progressive impairment of kidney function, which can accelerate the progression of cardiovascular disease, increase the risk of infection, and lead to related complications such as anemia and bone disease. CKD is to a great extent preventable and treatable, and it is particularly important to improve the early diagnosis, strengthen the research underlying the mechanism of disease occurrence and development, and innovate new intervention measures. Fibroblast growth factor 21 (FGF21) belongs to one of members of endocrine FGF subfamily with evolutionarily conserved functions and performs a vital role in the regulation of energy balance and adipose metabolism. FGF21 needs to rely on β-Klotho protein to specifically bind to FGF receptor (FGFR), which activates the FGF21 signaling exerting the biological function. FGF21 is deemed as an important regulatory factor extensively modulating many cellular functions under physiologic and pathologic conditions. Although the metabolic effect of FGF21 has been extensively studied, its potential biological role in the kidney has not been generally investigated. In this review, we summarize the biological characteristics, regulation and biological function of FGF21 based on the current studies, and briefly discuss the potential relationship with chronic kidney disease.

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Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects

Cited by 12 publications

References 38 publications

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study

Fibroblast growth factor 21 exerts a protective effect on diabetes-induced cognitive decline by remodeling cerebral glucose and neurotransmitter metabolism in mice

Regulation and Potential Biological Role of Fibroblast Growth Factor 21 in Chronic Kidney Disease

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