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>

Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Glucose Effectiveness ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

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 Exendin-4 Improves β-Cell Function in Autophagy-Deficient β-Cells

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4512-4524 ◽  
Author(s):  
Hiroko Abe ◽  
Toyoyoshi Uchida ◽  
Akemi Hara ◽  
Hiroki Mizukami ◽  
Koji Komiya ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Death ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Apoptotic Cell ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

Autophagy is cellular machinery for maintenance of β-cell function and mass. The implication of autophagy failure in β-cells on the pathophysiology of type 2 diabetes and its relation to the effect of treatment of diabetes remains elusive. Here, we found increased expression of p62 in islets of db/db mice and patients with type 2 diabetes mellitus. Treatment with exendin-4, a glucagon like peptide-1 receptor agonist, improved glucose tolerance in db/db mice without significant changes in p62 expression in β-cells. Also in β-cell-specific Atg7-deficient mice, exendin-4 efficiently improved blood glucose level and glucose tolerance mainly by enhanced insulin secretion. In addition, we found that exendin-4 reduced apoptotic cell death and increased proliferating cells in the Atg7-deficient islets, and that exendin-4 counteracted thapsigargin-induced cell death of isolated islets augmented by autophagy deficiency. Our results suggest the potential involvement of reduced autophagy in β-cell dysfunction in type 2 diabetes. Without altering the autophagic state in β-cells, exendin-4 improves glucose tolerance associated with autophagy deficiency in β-cells. This is mainly achieved through augmentation of insulin secretion. In addition, exendin-4 prevents apoptosis and increases the proliferation of β-cells associated with autophagy deficiency, also without altering the autophagic machinery in β-cells.

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.

Let7b-5p is Upregulated in the Serum of Emirati Patients with Type 2 Diabetes and Regulates Insulin Secretion in INS-1 Cells

2020 ◽  
Author(s):  
Hayat Aljaibeji ◽  
Noha Mousaad Elemam ◽  
Abdul Khader Mohammed ◽  
Hind Hasswan ◽  
Mahammad Al Thahyabat ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Viability ◽  
Cell Function ◽  
Serum Levels ◽  
Insulin Content ◽  
Β Cell ◽  
Control Subjects ◽  
Β Cell Function

Abstract Let7b-5p is a member of the Let-7 miRNA family and one of the top expressed miRNAs in human islets that implicated in glucose homeostasis. The levels of Let7b-5p in type 2 diabetes (T2DM) patients or its role in β-cell function is still unclear. In the current study, we measured the serum levels of let7b-5p in Emirati patients with T2DM (with/without complications) and control subjects. Overexpression or silencing of let7b-5p in INS-1 (832/13) cells was performed to investigate the impact on insulin secretion, content, cell viability, apoptosis, and key functional genes. We found that serum levels of let7b-5p are significantly (p<0.05) higher in T2DM-patients or T2DM with complications compared to control subjects. Overexpression of let7b-5p increased insulin content and decreased glucose-stimulated insulin secretion, whereas silencing of let7b-5p reduced insulin content and secretion. Modulation of the expression levels of let7b-5p did not influence cell viability nor apoptosis. Analysis of mRNA and protein expression of hallmark genes in let7b-5p transfected cells revealed a marked dysregulation of Insulin, Pancreatic And Duodenal Homeobox 1 (PDX1), glucokinase (GCK), glucose transporter 2 (GLUT2), and INSR. In conclusion, an appropriate level of let7b-5p is essential to maintain β-cell function and may be regarded as a biomarker for T2DM.

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