scholarly journals Circulating Retinol-Binding Protein 4 Is Inversely Associated With Pancreatic β-Cell Function Across the Spectrum of Glycemia

Diabetes Care ◽  
2020 ◽  
Vol 43 (6) ◽  
pp. 1258-1265
Author(s):  
Rong Huang ◽  
Songping Yin ◽  
Yongxin Ye ◽  
Nixuan Chen ◽  
Shiyun Luo ◽  
...  
Keyword(s):  
Cell Function ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Β Cell Function

scholarly journals Retinol-Binding Protein 4 Activates STRA6 Provoking Pancreatic β Cell Dysfunction in Type 2 Diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Rong Huang ◽  
Xinxiu Bai ◽  
Xueyan Li ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Cell Dysfunction ◽  
Β Cell Function

Pancreatic β cell dysfunction plays a decisive role in progression of type 2 diabetes. Retinol binding protein 4 (RBP4) is a prominent adipokine in type 2 diabetes while its effect on β cell function remains elusive and the underlying mechanisms are unknown. Here, we found that elevated circulating RBP4 levels were inversely correlated with pancreatic β cell function in db/db mice across different glycemic stages. RBP4 directly suppressed glucose stimulated insulin secretion (GSIS) in primary isolated islets and INS-1E cells in a dose- and time-dependent manner. RBP4-transgenic overexpressing mice (RBP4-Tg) showed a dynamic decrease of GSIS which appeared as early as 8-week-old preceding the impairment of insulin sensitivity and glucose tolerance. Islets isolated from RBP4-Tg mice showed a significant decrease of GSIS. Mechanistically, we demonstrated that the stimulated by retinoic acid 6(STRA6), RBP4’s only known specific membrane receptor, is expressed in β cells and mediates the inhibitory effect of RBP4 on insulin synthesis via JAK2/STAT1/ISL-1 pathway. Moreover, decreasing circulating RBP4 level could effectively restore β cell dysfunction and ameliorate hyperglycemia in db/db mice. These observations revealed a role of RBP4 in pancreatic β cell dysfunction which provided new insight into the diabetogenic effect of RBP4.

scholarly journals Retinol-Binding Protein 4 Activates STRA6 Provoking Pancreatic β Cell Dysfunction in Type 2 Diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Rong Huang ◽  
Xinxiu Bai ◽  
Xueyan Li ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Cell Dysfunction ◽  
Β Cell Function

Pancreatic β cell dysfunction plays a decisive role in progression of type 2 diabetes. Retinol binding protein 4 (RBP4) is a prominent adipokine in type 2 diabetes while its effect on β cell function remains elusive and the underlying mechanisms are unknown. Here, we found that elevated circulating RBP4 levels were inversely correlated with pancreatic β cell function in db/db mice across different glycemic stages. RBP4 directly suppressed glucose stimulated insulin secretion (GSIS) in primary isolated islets and INS-1E cells in a dose- and time-dependent manner. RBP4-transgenic overexpressing mice (RBP4-Tg) showed a dynamic decrease of GSIS which appeared as early as 8-week-old preceding the impairment of insulin sensitivity and glucose tolerance. Islets isolated from RBP4-Tg mice showed a significant decrease of GSIS. Mechanistically, we demonstrated that the stimulated by retinoic acid 6(STRA6), RBP4’s only known specific membrane receptor, is expressed in β cells and mediates the inhibitory effect of RBP4 on insulin synthesis via JAK2/STAT1/ISL-1 pathway. Moreover, decreasing circulating RBP4 level could effectively restore β cell dysfunction and ameliorate hyperglycemia in db/db mice. These observations revealed a role of RBP4 in pancreatic β cell dysfunction which provided new insight into the diabetogenic effect of RBP4.

Retinol-binding Protein 4 in Rheumatoid Arthritis-related Insulin Resistance and β-cell Function

2014 ◽  
Vol 41 (4) ◽  
pp. 658-665 ◽  
Author(s):  
Iván Ferraz-Amaro ◽  
Miguel A. González-Gay ◽  
Federico Diaz-González
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Cell Function ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Β Cell ◽  
C Peptide ◽  
Retinol Binding Protein 4 ◽  
Significant Difference ◽  
Β Cell Function

Objective.Retinol-binding protein 4 (RBP4), an adipokine related to impaired glucose tolerance, has been associated with insulin resistance (IR) and β-cell function in subjects with obesity or diabetes. In our study we assessed RBP4 levels in patients with rheumatoid arthritis (RA). We also determined whether any correlation exists between RBP4 levels and the presence of IR in these patients.Methods.Plasma RBP4, insulin, C-peptide concentrations, and homeostasis model assessment (HOMA)-IR were measured in 101 patients with RA and 115 sex-matched and age-matched controls. A multivariable analysis adjusted for IR classic cardiovascular risk factors and body mass index was performed to establish the correlation between RBP4 plasma concentrations and features of IR in RA. Data were adjusted for glucocorticoid intake in patients with RA.Results.Patients had higher levels of insulin, C-peptide levels, HOMA-percentage of β-cell secretion (%B) index, and HOMA-IR index than controls. RBP4 levels were significantly lower in the whole group of patients than in controls [13.99 (9.78–19.88) vs 21.50 (10.28–32.59) μg/ml, p < 0.01]. However, only those who were glucocorticoid-naive showed significant difference in RBP4 plasma concentration when compared to controls [11.88 (7.93–17.96) vs 21.50 (10.28–32.59) μg/ml, p < 0.01]. The HOMA-%B [log β coefficient 0.00 (0.00–0.01), p < 0.01] showed positive relationships regarding RBP4 in controls. That was not the case in patients with RA [log β coefficient 0.00 (−0.0–0.00), p = 0.93 for HOMA-%B].Conclusion.RBP4 does not correlate with the presence of IR and β-cell function in patients with RA. The mechanisms leading to IR in RA may be different from those occurring in obesity or diabetes.

scholarly journals Circulating Retinol Binding Protein 4 is Inversely Associated with Pancreatic β Cell Function across the Spectrum of Glycemia

2020 ◽  
Author(s):  
Rong Huang ◽  
Songping Yin ◽  
Yongxin Ye ◽  
Nixuan Chen ◽  
Shiyun Luo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Retinol Binding Protein ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Β Cell Function ◽  
Oral Minimal Model

<p>OBJECTIVE: The aim of this study was to examine the association of circulating retinol binding protein 4 (RBP4) levels with β cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 291 subjects aged 35-60 with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT) and type 2 diabetes were screened by standard 2-h oral glucose tolerance test (2-h OGTT) with the use of traditional measures to evaluate β cell function. 74 subjects from these participants were recruited in oral minimal model test and assessed β cell function with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. RESULTS: Circulating RBP4 levels were significantly and inversely correlated with β cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indexes, but not with HOMA-β, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion (DI-PhiT). CONCLUSION: Circulating RBP4 levels are inversely and independently correlated with β cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.</p>

scholarly journals Circulating Retinol Binding Protein 4 is Inversely Associated with Pancreatic β Cell Function across the Spectrum of Glycemia

2020 ◽  
Author(s):  
Rong Huang ◽  
Songping Yin ◽  
Yongxin Ye ◽  
Nixuan Chen ◽  
Shiyun Luo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Retinol Binding Protein ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Β Cell Function ◽  
Oral Minimal Model

<p>OBJECTIVE: The aim of this study was to examine the association of circulating retinol binding protein 4 (RBP4) levels with β cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 291 subjects aged 35-60 with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT) and type 2 diabetes were screened by standard 2-h oral glucose tolerance test (2-h OGTT) with the use of traditional measures to evaluate β cell function. 74 subjects from these participants were recruited in oral minimal model test and assessed β cell function with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. RESULTS: Circulating RBP4 levels were significantly and inversely correlated with β cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indexes, but not with HOMA-β, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion (DI-PhiT). CONCLUSION: Circulating RBP4 levels are inversely and independently correlated with β cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.</p>

scholarly journals Circulating Retinol Binding Protein 4 is Inversely Associated with Pancreatic β Cell Function across the Spectrum of Glycemia

2020 ◽  
Author(s):  
Rong Huang ◽  
Songping Yin ◽  
Yongxin Ye ◽  
Nixuan Chen ◽  
Shiyun Luo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Retinol Binding Protein ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Β Cell Function ◽  
Oral Minimal Model

<p><b>OBJECTIVE:</b> The aim of this study was to examine the association of circulating retinol binding protein 4 (RBP4) levels with β cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. </p><p><b>RESEARCH DESIGN AND METHODS:</b> A total of 291 subjects aged 35-60 with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT) and type 2 diabetes were screened by standard 2-h oral glucose tolerance test (2-h OGTT) with the use of traditional measures to evaluate β cell function. 74 subjects from these participants were recruited in oral minimal model test and assessed β cell function with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. </p><p><b>RESULTS:</b> Circulating RBP4 levels were significantly and inversely correlated with β cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indexes, but not with HOMA-β, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion (DI-PhiT). </p><p><b>CONCLUSION:</b> Circulating RBP4 levels are inversely and independently correlated with β cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.</p>

scholarly journals Circulating Retinol Binding Protein 4 is Inversely Associated with Pancreatic β Cell Function across the Spectrum of Glycemia

2020 ◽  
Author(s):  
Rong Huang ◽  
Songping Yin ◽  
Yongxin Ye ◽  
Nixuan Chen ◽  
Shiyun Luo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Retinol Binding Protein ◽  
Β Cell ◽  
Retinol Binding Protein 4 ◽  
Β Cell Function ◽  
Oral Minimal Model

<p><b>OBJECTIVE:</b> The aim of this study was to examine the association of circulating retinol binding protein 4 (RBP4) levels with β cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. </p><p><b>RESEARCH DESIGN AND METHODS:</b> A total of 291 subjects aged 35-60 with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT) and type 2 diabetes were screened by standard 2-h oral glucose tolerance test (2-h OGTT) with the use of traditional measures to evaluate β cell function. 74 subjects from these participants were recruited in oral minimal model test and assessed β cell function with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. </p><p><b>RESULTS:</b> Circulating RBP4 levels were significantly and inversely correlated with β cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indexes, but not with HOMA-β, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion (DI-PhiT). </p><p><b>CONCLUSION:</b> Circulating RBP4 levels are inversely and independently correlated with β cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.</p>

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

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