Dataset Information

Serum fatty acid-binding protein 4 levels and responses of pancreatic islet β-cells and α-cells in patients with type 2 diabetes.

ABSTRACT:

Background

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. So the present study was to investigate the serum FABP4 levels and responses of islet β-cells and α-cells in patients with T2D.

Methods

115 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 (ISI_M-cp) and ratio of the area under the C peptide curve to the glucose curve (AUC_cp/glu) during OGTT, respectively. Fasting glucagon (Gluca_0min) and postchallenge glucagon assessed by the area under the glucagon curve (AUC_gluca) 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.

Results

The 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 lnISI_M-cp (r = - 0.332, p < 0.001) and positively correlated with lnAUC_cp/glu (r = 0.324, p < 0.001), lnGluca_0min (r = 0.200, p = 0.040) and lnAUC_gluca (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 lnISI_M-cp (β = - 0.296, t = - 2.900, p = 0.005), lnAUC_cp/glu (β = 0.223, t = 2.038, p = 0.046), lnGluca_0min (β = 0.272, t = 2.330, p = 0.024) and lnAUC_gluca (β = 0.341, t = 3.065, p = 0.004), respectively.

Conclusion

Increased serum FABP4 levels were closely associated with blunted insulin sensitivity, increased insulin secretion, and elevated fasting and postchallenge glucagon levels in patients with T2D.

SUBMITTER: Wang H

PROVIDER: S-EPMC8234651 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveThe insulin-pancreatic acinar axis may play a major role in pancreatic function. Amylase is an exocrine enzyme that is produced by pancreatic acinar cells, and low serum amylase levels may be associated with endocrine diseases, such as metabolic syndrome and diabetes. We hypothesized that low serum amylase levels may be associated with impaired islet β cell function in type 2 diabetes. Therefore, we investigated the relationship between the serum amylase levels and islet β cell function in patients with early type 2 diabetes.MethodsThe cross-sectional study recruited 2327 patients with a mean of 1.71±1.62 years since their diagnosis of type 2 diabetes, and all participants were treated with lifestyle intervention alone. Serum amylase levels, the 75-g oral glucose tolerance test (OGTT) and metabolic risk factors were examined in all participants. The insulin sensitivity index (Matsuda index, ISIMatsuda) and insulin secretion index (ratio of total area-under-the-insulin-curve to glucose-curve, AUCins/glu) were derived from the OGTT. Integrated islet β cell function was assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2) (ISIMatsuda multiplied by AUCins/glu).ResultsSerum amylase levels in the normal range were significantly correlated with ISIMatsuda, AUCins/glu and ISSI-2 (r = 0.203, 0.246 and 0.413, respectively, p<0.001). The association of the serum amylase levels with ISSI-2 (adjusted r = 0.363, p<0.001) was closer than the association with ISIMatsuda (adjusted r = 0.191, p<0.001) and AUCins/glu (adjusted r = 0.174, p<0.001) after adjusting for the anthropometric indices, time since the diagnosis of diabetes, lipid profiles, uric acid levels, estimated glomerular filtration rate, HbA1c levels, smoking and drinking using the partial correlation test. After adjusting for these metabolic risk factors in the multivariate regression analysis with the amylase levels as the dependent variable, ISSI-2 was the major independent contributor to the serum amylase levels (β = 0.416, t = 21.72, p<0.001). Meanwhile, in a comparison of the groups with the highest and lowest quartiles of serum amylase levels, the mean difference in logISSI-2 was 0.902 (95% CI 0.823 to 0.982), and after adjusting for metabolic risk factors, the mean difference in logISSI-2 was 0.610 (0.537 to 0.683).ConclusionsSerum amylase levels in the normal range are positively associated with integrated islet β cell function in patients with early type 2 diabetes, as assessed by ISSI-2.

Project description:BackgroundAccompanying islet α- and β-cell dysregulation in type 2 diabetes (T2D) at the microscopic scale, alterations in body composition at the macroscopic scale may affect the pathogenesis of T2D. However, the connections between body composition and islet α-cell and β-cell functions in T2D have not been thoroughly explored.MethodsFor this cross-sectional study, we recruited a total of 729 Chinese Han patients with T2D in a consecutive manner. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition, which included total bone-free mass, total fat and lean mass, trunk fat and lean mass and limb fat and lean mass. Every patient underwent an oral glucose tolerance test to simultaneously detect glucose, C-peptide and glucagon. The indices of islet α-cell function included fasting glucagon levels and the area under the curve of glucagon after a challenge (AUCglucagon), while the indices of β-cell function included the insulin sensitivity index derived from C-peptide (ISIC-peptide) and the area under the curve of C-peptide after a challenge (AUCC-peptide).ResultsAmong all patients, fat mass, especially trunk fat mass, was significantly correlated with ISIC-peptide and AUCC-peptide levels (r = - 0.330 and 0.317, respectively, p < 0.001), while lean mass, especially limb lean mass, was significantly correlated with fasting glucagon and AUCglucagon levels (r = - 0.196 and - 0.214, respectively, p < 0.001). Moreover, after adjusting for other relevant variables via multivariate linear regression analysis, increased trunk fat mass was independently associated with decreased ISIC-peptide (β = - 0.247, t = - 3.628, p < 0.001, partial R2 = 10.9%) and increased AUCC-peptide (β = 0.229, t = 3.581, p < 0.001, partial R2 = 8.2%), while decreased limb lean mass was independently associated with increased fasting glucagon (β = - 0.226, t = - 2.127, p = 0.034, partial R2 = 3.8%) and increased AUCglucagon (β = - 0.218, t = - 2.050, p = 0.041, partial R2 = 2.3%). Additionally, when separate analyses were performed with the same concept for both sexes, we found that increased trunk fat mass was still independently associated with decreased ISIC-peptide and increased AUCC-peptide, while decreased limb lean mass was still independently associated with increased fasting glucagon and AUCglucagon.ConclusionsIncreased trunk fat mass may partly account for decreased insulin sensitivity and increased insulin secretion, while decreased limb lean mass may be connected to increased fasting glucagon and postprandial glucagon secretion.

Project description:C-X-C Motif Chemokine Ligand 10 (CXCL10) is a pro-inflammatory chemokine specifically recognized by the ligand receptor CXCR3 which is mostly expressed in T-lymphocytes. Although CXCL10 expression and secretion have been widely associated to pancreatic islets both in non-obese diabetic (NOD) mice and in human type 1 diabetic (T1D) donors, the specific expression pattern among pancreatic endocrine cell subtypes has not been clarified yet. Therefore, the purpose of this study was to shed light on the pancreatic islet expression of CXCL10 in NOD, in C57Bl/6J and in NOD-SCID mice as well as in human T1D pancreata from new-onset T1D patients (DiViD study) compared to non-diabetic multiorgan donors from the INNODIA European Network for Pancreatic Organ Donors with Diabetes (EUnPOD). CXCL10 was expressed in pancreatic islets of normoglycaemic and new-onset diabetic NOD mice but not in C57Bl/6J and NOD-SCID mice. CXCL10 expression was increased in pancreatic islets of new-onset diabetic NOD mice compared to normoglycaemic NOD mice. In NOD mice, CXCL10 colocalized both with insulin and glucagon. Interestingly, CXCL10-glucagon colocalization rate was significantly increased in diabetic vs. normoglycaemic NOD mouse islets, indicating an increased expression of CXCL10 also in alpha-cells. CXCL10 was expressed in pancreatic islets of T1D patients but not in non-diabetic donors. The analysis of the expression pattern of CXCL10 in human T1D pancreata from DiViD study, revealed an increased colocalization rate with glucagon compared to insulin. Of note, CXCL10 was also expressed in alpha-cells residing in insulin-deficient islets (IDI), suggesting that CXCL10 expression in alpha cells is not driven by residual beta-cells and therefore may represent an independent phenomenon. In conclusion, we show that in T1D CXCL10 is expressed by alpha-cells both in NOD mice and in T1D patients, thus pointing to an additional novel role for alpha-cells in T1D pathogenesis and progression.