Fıbroblast growth factor 21 and ıts relatıonshıp wıth ınsulın sensıtıvıty ın fırst-degree relatıves of patıents wıth type 2 dıabetes mellıtus

Ors, Damla; Altınova, Alev Eroğlu; Yalcin, Mehmet Muhittin; Gülbahar, Özlem; Aktürk, Müjde; Arslan, Metin; Törüner, Füsun Baloş

doi:10.5603/ep.a2016.0016

Cited by 4 publications

(9 citation statements)

References 25 publications

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“…Type 2 diabetes mellitus (T2DM) is the predominant form of diabetes and is characterized by insulin resistance and pancreatic β‐cell failure, which lead to abnormally high blood glucose levels (hyperglycaemia) . Impaired function of β‐cells, which are responsible for the production and secretion of insulin, is a critical contributing factor for the progression from prediabetes to diabetes .…”

Section: Introductionmentioning

confidence: 99%

“…failure, which lead to abnormally high blood glucose levels (hyperglycaemia). 1,2 Impaired function of β-cells, which are responsible for the production and secretion of insulin, is a critical contributing factor for the progression from prediabetes to diabetes. 3,4 The loss of responding β-cells in pancreatic islets has been found in genetically diabetic (db/db) mice.…”

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confidence: 99%

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Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling‐dependent manner

Pan

Wang

Zheng

et al. 2018

J Cellular Molecular Medi

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Fibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down‐regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet β‐cell function. Importantly, FGF21 knockout exacerbated palmitate‐induced islet β‐cell failure and suppression of glucose‐stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced β‐cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3‐kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21‐induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21‐induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling‐dependent insulin expression and secretion.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling‐dependent manner

Pan

Wang

Zheng

et al. 2018

J Cellular Molecular Medi

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“…Nowadays, there are no data showing changes in FGF23 and Klotho concentrations in people with type 1 diabetes. The literature reports that protein concentrations from the fibroblast growth factor family are increased in first-degree relatives of DM2 patients with pre-diabetes and that there is a strong association between fibroblast growth factor 21 (FGF 21) and obesity and insulin sensitivity [55]. We know that Klotho levels among patients with type 1 diabetes mellitus might be affected by renal impairment, hyperglycaemia, and high insulin doses [56].…”

Section: Discussionmentioning

confidence: 99%

Klotho protein function among patients with type 1 diabetes

Flotyńska

Uruska

Araszkiewicz

et al. 2018

Endokrynologia Polska

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The fibroblast growth factor 23 (FGF23) and Klotho system play a very important role in the regulation of the human body metabolism. On the one hand, they promote longevity, and on the other hand they promote insulin resistance. Nowadays, accelerated aging in diabetes as the main consequence of chronic complications of the disease is postulated. Signalling pathways induced by insulin, insulin-like growth factor (IGF-1), and their homologues play an important role in controlling the aging process. Because FGF23/Klotho system affects glucose metabolism and gene expression of antioxidant enzymes, changes in its concentration may be a marker of chronic complications of diabetes or a treatment option. Despite huge improvements in the treatment of diabetes, its chronic complications remain an important clinical problem. An interesting issue is the relationship between the concentration of FGF23/Klotho and management of the disease, duration, insulin resistance, and development of complications in type 1 diabetes. (Endokrynol Pol 2018; 69 (6): 696-704)

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“…FGF‐2 is one of the most studied FGFs, involved in various endocrine signaling trails, serum phosphate regulation, angiogenesis, wound healing, and embryonic development; additionally, FGF‐2 plays a significant role in the morphogenesis, bone signaling, and cartilage metabolism . Among all these features, FGF‐2 was also shown to (1) influence cell proliferation and stimulate DNA synthesis; (2) mediate the metabolic function of tissues, leading to repair by its releasing from the extracellular matrix (ECM) and regeneration of lost tissues, being used against different cardiovascular disorders; and (3) augment ECM synthesis …”

Section: Introductionmentioning

confidence: 99%

“…FGF-2 is one of the most studied FGFs, [10][11][12][13][14] involved in various endocrine signaling trails, serum phosphate regulation, angiogenesis, wound healing, and embryonic development; [12][13][14][15][16][17] additionally, FGF-2 plays a significant role in the morphogenesis, bone signaling, and cartilage metabolism. [10][11][12][13][14][17][18][19][20][21][22] Among all these features, FGF-2 was also shown to (1) influence cell proliferation 23 and stimulate DNA synthesis; 24 (2) mediate the metabolic function of tissues, leading to repair by its releasing from the extracellular matrix (ECM) and regeneration of lost tissues, being used against different cardiovascular disorders; 25 and (3) augment ECM synthesis. 26 One of the FGF binding partners are GAGs-long-unbranched polysaccharides exhibiting a repeating disaccharide unit, being the major components of the ECM, responsible for a variety of biological activities of proteoglycans (PG).…”

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confidence: 99%

Chip‐based high resolution tandem mass spectrometric determination of fibroblast growth factor—chondroitin sulfate disaccharides noncovalent interaction

et al. 2018

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Fibroblast growth factor-2 (FGF-2) is involved in wound healing and embryonic development. Glycosaminoglycans (GAGs), the major components of the extracellular matrix (ECM), play fundamental roles at this level. FGF-GAG noncovalent interactions are in the focus of research, due to their influence upon cell proliferation and tissue regeneration. Lately, high resolution mass spectrometry (MS) coupled with chip-nanoelectrospray (nanoESI) contributed a significant progress in glycosaminoglycomics by discoveries related to novel species and their characterization. We have employed a fully automated chip-nanoESI coupled to a quadrupole time-of-flight (QTOF) MS for assessing FGF-GAG noncovalent complexes. For the first time, a CS disaccharide was involved in a binding assay with FGF-2. The experiments were conducted in 10 mM ammonium acetate/formic acid, pH 6.8, by incubating FGF-2 and CS in buffer. The detected complexes were characterized by top-down in tandem MS (MS/MS) using collision induced-dissociation (CID). CID MS/MS provided data showing for the first time that the binding process occurs via the sulfate group located at C4 in GalNAc. This study has demonstrated that chip-MS may generate reliable data upon the formation of GAG-protein complexes and their structure. Biologically, the findings are relevant for studies focused on the identification of the active domains in longer GAG chains.

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Fıbroblast growth factor 21 and ıts relatıonshıp wıth ınsulın sensıtıvıty ın fırst-degree relatıves of patıents wıth type 2 dıabetes mellıtus

Cited by 4 publications

References 25 publications

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling‐dependent manner

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling‐dependent manner

Klotho protein function among patients with type 1 diabetes

Chip‐based high resolution tandem mass spectrometric determination of fibroblast growth factor—chondroitin sulfate disaccharides noncovalent interaction

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