Abstract
BackgroundSerum fatty acid-binding protein 4 (FABP4), as an intracellular lipid chaperone and adipokine, was reported to be related to the incidence of type 2 diabetes (T2D) and diabetic complications, but its association with pancreatic islet β-cell and α-cell functions has not been fully elucidated. So the present study was to investigate the serum FABP4 levels and responses of islet β-cells and α-cells in patients with T2D.Methods115 patients with T2D and 89 healthy controls (HC), who received serum FABP4 levels test, were recruited to participate in this study. Moreover, 75-g oral glucose tolerance test (OGTT) was performed in T2D patients to evaluate islet β-cell and α-cell functions. Systemic insulin sensitivity and overall insulin secretion of islet β-cell function were assessed by Matsuda index using C peptide (ISIM-cp) and ratio of the area under the C peptide curve to the glucose curve (AUCcp/glu) during OGTT, respectively. Fasting glucagon (Gluca0min) and postchallenge glucagon assessed by the area under the glucagon curve (AUCgluca) were determined during OGTT to evaluate islet α-cell function. And other various clinical variables were also measured in all participants. Skewed variables were natural log-transformed (ln), such as lnFABP4.ResultsThe serum FABP4 levels in T2D patients were significantly higher than those in HC (p < 0.05). And after partially adjusting for fasting plasma glucose, serum lnFABP4 levels were negatively correlated with lnISIM-cp (r = − 0.332, p < 0.001) and positively correlated with lnAUCcp/glu (r = 0.324, p < 0.001), lnGluca0min (r = 0.200, p = 0.040) and lnAUCgluca (r = 0.311, p < 0.001), respectively, in patients with T2D. Furthermore, when multiple linear regression analyses were applied to adjust for other various clinical variables, serum lnFABP4 levels were found to remain associated with lnISIM-cp (β = − 0.296, t = − 2.900, p = 0.005), lnAUCcp/glu (β = 0.223, t = 2.038, p = 0.046), lnGluca0min (β = 0.272, t = 2.330, p = 0.024) and lnAUCgluca (β = 0.341, t = 3.065, p = 0.004), respectively.ConclusionIncreased serum FABP4 levels were closely associated with blunted insulin sensitivity, increased insulin secretion, and elevated fasting and postchallenge glucagon levels in patients with T2D.
Highlights
Serum fatty acid-binding protein 4 (FABP4), as an intracellular lipid chaperone and adipokine, was reported to be related to the incidence of type 2 diabetes (T2D) and diabetic complications, but its association with pancreatic islet β-cell and α-cell functions has not been fully elucidated
There were no differences in age, diastolic blood pressure (DBP), TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), estimated glomerular filtration rate (eGFR) and serum uric acid (UA) between the healthy controls (HC) and patients with T2D
The main findings of our study were as follows: first, patients with T2D were presented with a higher levels of serum FABP4 when compared to healthy subjects; second, serum FABP4 levels were positively correlated with LDLC in healthy subjects and positively correlated with UA and fasting plasma glucose (FPG) in patients with T2D; third, correlations of serum FABP4 levels with Matsuda index using C peptide (ISIM-cp), AUCcp/glu, Gluca0min and AUCgluca became more evident when partially adjusted for FPG; fourth, after adjusting for other various clinical variables, serum FABP4 levels were found to remain associated with ISIM-cp, AUCcp/glu, Gluca0min and AUCgluca
Summary
Serum fatty acid-binding protein 4 (FABP4), as an intracellular lipid chaperone and adipokine, was reported to be related to the incidence of type 2 diabetes (T2D) and diabetic complications, but its association with pancreatic islet β-cell and α-cell functions has not been fully elucidated. The present study was to investigate the serum FABP4 levels and responses of islet β-cells and α-cells in patients with T2D. Circulating FABP4 mainly secreted from adipocytes and macrophages seems to function as lipid chaperone for the fatty acids transportation, storage and metabolism in target organs, and serves as a bioactive adipokine in several target cells, including adipocytes, macrophages, endothelial cells, etc [8]
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