Obstructive Sleep Apnea, Glucose Tolerance, and β-Cell Function in Adults With Prediabetes or Untreated Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study

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.

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

10.2337/dc20-1234/suppl.11985918.v1 ◽

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

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.

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

Endocrinology ◽

10.1210/en.2013-1578 ◽

2013 ◽

Vol 154 (12) ◽

pp. 4512-4524 ◽

Cited By ~ 35

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.

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

10.2337/dc20-1234/suppl.11985918 ◽

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

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.

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Impact of Obstructive Sleep Apnea and Sleep Duration on Glucose Tolerance and Beta-Cell Function in Adults with Prediabetes or Untreated Type 2 Diabetes

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a7483 ◽

2019 ◽

Author(s):

B. Mokhlesi ◽

A.H. Tjaden ◽

K.A. Temple ◽

S.L. Edelstein ◽

S. Sam ◽

...

Keyword(s):

Type 2 Diabetes ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Glucose Tolerance ◽

Beta Cell ◽

Sleep Duration ◽

Beta Cell Function ◽

Cell Function ◽

Obstructive Sleep

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

10.2337/figshare.11985918 ◽

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

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.

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

10.2337/figshare.11985918.v1 ◽

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

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.

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

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1261-5282 ◽

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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Dual Mechanism for Type-2 Diabetes Resolution after Roux-en-Y Gastric Bypass

The American Surgeon ◽

10.1177/000313480907500608 ◽

2009 ◽

Vol 75 (6) ◽

pp. 498-503 ◽

Cited By ~ 10

Author(s):

Edward Lin ◽

S. Scott Davis ◽

Jahnavi Srinivasan ◽

John F. Sweeney ◽

Thomas R. Ziegler ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Gastric Bypass ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Peripheral Insulin Resistance

Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose-insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.

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