Quantitative indexes of β-cell function during graded up&down glucose infusion from C-peptide minimal models

2001 ◽  
Vol 280 (1) ◽  
pp. E2-E10 ◽  
Author(s):  
Gianna Toffolo ◽  
Elena Breda ◽  
Melissa K. Cavaghan ◽  
David A. Ehrmann ◽  
Kenneth S. Polonsky ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Minimal Model ◽  
Cell Function ◽  
Glucose Infusion ◽  
Β Cell ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Β Cell Function ◽  
Quantitative Indexes ◽  
Infusion Protocol

Availability of quantitative indexes of insulin secretion is important for definition of the alterations in β-cell responsivity to glucose associated with different physiopathological states. This is presently possible by using the intravenous glucose tolerance test (IVGTT) in conjunction with the C-peptide minimal model. However, the secretory response to a more physiological slowly increasing/decreasing glucose stimulus may uncover novel features of β-cell function. Therefore, plasma C-peptide and glucose data from a graded glucose infusion protocol (seven 40-min periods of 0, 4, 8, 16, 8, 4, and 0 mg · kg−1 · min−1) in eight normal subjects were analyzed by use of a new model of insulin secretion and kinetics. The model assumes a two-compartment description of C-peptide kinetics and describes the stimulatory effect on insulin secretion of both glucose concentration and the rate at which glucose increases. It provides in each individual the insulin secretion profile and three indexes of pancreatic sensitivity to glucose: Φs, Φd, and Φb, related, respectively, to the control of insulin secretion by the glucose level (static control), the rate at which glucose increases (dynamic control), and basal glucose. Indexes (means ± SE) were Φs = 18.8 ± 1.8 (109min−1), Φd = 222 ± 30 (109), and Φb = 5.2 ± 0.4 (109 min−1). The model also allows one to quantify the β-cell times of response to increasing and decreasing glucose stimulus, equal to 5.7 ± 2.2 (min) and 17.8 ± 2.0 (min), respectively. In conclusion, the graded glucose infusion protocol, interpreted with a minimal model of C-peptide secretion and kinetics, provides a quantitative assessment of pancreatic function in an individual. Its application to various physiopathological states should provide novel insights into the role of insulin secretion in the development of glucose intolerance.

Minimal modeling of insulin secretion in the perfused rat pancreas: a drug effect case study

2014 ◽  
Vol 306 (6) ◽  
pp. E627-E634 ◽  
Author(s):  
Michela Riz ◽  
Morten Gram Pedersen ◽  
Gianna Maria Toffolo ◽  
Guido Haschke ◽  
Hans-Christoph Schneider ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Minimal Model ◽  
Cell Function ◽  
Fold Increase ◽  
Second Phase ◽  
Good Precision ◽  
Β Cell ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Β Cell Function

The experimental protocol of the perfused rat pancreas is commonly used to evaluate β-cell function. In this context, mathematical models become useful tools through the determination of indexes that allow the assessment of β-cell function in different experimental groups and the quantification of the effects of antidiabetic drugs, secretagogues, or treatments. However, a minimal model applicable to the isolated perfused rat pancreas has so far been unavailable. In this work, we adapt the C-peptide minimal model applied previously to the intravenous glucose tolerance test to obtain a specific model for the experimental settings of the perfused pancreas. Using the model, it is possible to estimate indexes describing β-cell responsivity for first (ΦD) and second phase (ΦS, T) of insulin secretion. The model was initially applied to untreated pancreata and afterward used for the assessment of pharmacologically relevant agents (the gut hormone GLP-1, the potent GLP-1 receptor agonist lixisenatide, and a GPR40/FFAR1 agonist, SAR1) to quantify and differentiate their effect on insulin secretion. Model fit was satisfactory, and parameters were estimated with good precision for both untreated and treated pancreata. Model application showed that lixisenatide reaches improvement of β-cell function similarly to GLP-1 (11.7- vs. 13.1-fold increase in ΦD and 2.3- vs. 2.8-fold increase in ΦS) and demonstrated that SAR1 leads to an additional improvement of β-cell function in the presence of postprandial GLP-1 levels.

Effect of sham-feeding on glucose tolerance and insulin secretion

1987 ◽  
Vol 115 (1) ◽  
pp. 84-86 ◽  
Author(s):  
M. Lorentzen ◽  
S. Madsbad ◽  
H. Kehlet ◽  
B. Tronier
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Sham Feeding ◽  
C Peptide ◽  
Β Cell Function ◽  
Vagal Reflex ◽  
Normal Males

Abstract. Glucose, 25 g, was infused iv with or without sham-feeding in seven normal males. Sham-feeding improved glucose tolerance, incremental area of blood glucose being 63% (P < 0.05) of that during iv glucose without sham-feeding. The actual insulin secretion evaluated from the total area under the C-peptide and insulin curves did not differ during iv glucose with or without sham-feeding. These results suggest that the cephalic-vagal reflex improves glucose tolerance during iv glucose, independent of changes in β-cell function.

β- Cell function in a sample of Iraqi Patients with type 2 diabetes mellitus

2018 ◽  
pp. 68-72
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Function ◽  
Newly Diagnosed ◽  
Β Cell ◽  
C Peptide ◽  
Peptide Level ◽  
Β Cell Function ◽  
High Level

Back ground: Type 2 diabetes is mostly due to impaired β-cell mass and dysfunction which expressed by Insulin secretion, sensitivity and resistance. Aim of study: to evaluate β- cell function in newly diagnosed and ongoing diabetics. Method: Eighty-eight subjects enrolled in this study with age range (30-59) years, (20) healthy individuals as controls group with mean age (42.95±9.80) years. (68) Diabetic Patients was divided into two groups, (26) newly diagnosed diabetic, mean age (45.81±8.16) years and (42) ongoing diabetics, mean age (49.33±6.64) year. "Fasting glucose", "lipid profile", "glycosylated hemoglobin", "C-peptide levels" were evaluated. Insulin secretion, sensitivity and resistance "HOMA B %", "HOMA S %"and "HOMA IR" respectively were estimated by "Homeostasis Model Assessment" "HOMA2 calculator program". Results: "Insulin secretion" and "sensitivity" were found to be lower (P 0.001) in both groups of diabetes than that controls, while a high level of insulin resistance in both diabetic groups than controls (P>0.0001)."C-peptide" level is higher in "newly diagnosed" diabetics than" ongoing diabetics" and controls (p˂0.0001). Conclusion: Patients with low c- peptide level has poor insulin reserve and may need insulin while patients with high level of c- peptide have good insulin reserve and not need insulin to control his blood glucose.

scholarly journals Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice

2015 ◽  
Vol 228 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Linda Ahlkvist ◽  
Bilal Omar ◽  
Anders Valeur ◽  
Keld Fosgerau ◽  
Bo Ahrén
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Function ◽  
Receptor Activation ◽  
Oral Glucose ◽  
Β Cell ◽  
Glucagon Receptor ◽  
Intravenous Glucose ◽  
Β Cell Function

Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes.

scholarly journals FRI0322 INSULIN RESISTANCE IN NON-DIABETES PATIENTS WITH SPONDYLOARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 752.2-753
Author(s):  
J. C. Quevedo-Abeledo ◽  
F. Genre ◽  
J. Rueda-Gotor ◽  
A. Corrales ◽  
V. Hernández-Hernández ◽  
...  
Keyword(s):  
Cell Function ◽  
Inflammatory Diseases ◽  
Univariate Analysis ◽  
Serum Levels ◽  
Β Cell ◽  
Related Factors ◽  
C Peptide ◽  
Related Data ◽  
Β Cell Function ◽  
Beta Coefficient

Background:Insulin resistance (IR) is a state in which a given concentration of insulin is associated with a subnormal glucose response. IR constitutes a major underlying abnormality driving cardiovascular disease in the general population and has been linked to inflammatory diseases. In this sense, several reports have confirmed that inflammation worsens IR and impairs pancreatic β-cell function in inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.Objectives:In this study we aimed to determine the prevalence of IR in patients with spondyloarthritis (SpA) compared to controls, and whether IR can be explained by disease-related features in SpA patients.Methods:Study of 577 subjects, 306 patients diagnosed with SpA according to ASAS criteria and 271 controls. Insulin and C-peptide serum levels, IR and β-cell function (%B) indexes by homeostatic model assessment (HOMA2), and lipid profiles were assessed in patients and controls. A multivariate regression analysis was performed to evaluate the differences in IR indexes between patients and controls and to determine how IR is associated with disease-related characteristics.Results:SpA patients showed higher serum levels of insulin (8.7 [4.8-15.9] vs. 8.0 [5.7-11.2] uU/ml, p=0.001) and C peptide (1.4 [0.7-2.5] vs. 1.2 [0.7-1.7] ng/ml, p=0.000) than controls in the univariate analysis. Similarly, HOMA2-B% and IR were all significantly higher in SpA patients. These differences were still evident when the comparisons were made after the multivariate analysis had been adjusted for traditional IR-related factors (sex, age, BMI, hypertension, dyslipidemia, smoking and, cholesterol), glucocorticoids intake, insulin and C-peptide. Moreover, HOMA2-B% and HOMA2-IR scores, both calculated with insulin or C-peptide, yielded statistically higher significant values in SpA patients than controls.Classic IR-related factors (age, BMI, waist circumference, hypertension, obesity, dyslipidemia, atherogenic index, and triglycerides), as well as CRP serum levels, were all related, to a greater or lesser degree, with IR and β-cell function. Regarding disease-related data, ASDAS-CRP, BASFI and BASMI scores were positively associated with IR; and BASMI and BASDAI scores were positively related to HOMA2-%B-C peptide. Moreover, the use of NSAID and prednisone were, respectively, positive and negatively related to β-cell function. However, only some of the associations of the univariate analysis were maintained after adjusting for confounders. In this sense, disease duration (beta coefficient 2 [95% CI 1-3], p=0.001) and positivity for HLA-B27 (beta coefficient 30 [95% CI 12-49], p=0.002) were associated with higher β-cell functionality after the multivariate analysis.Conclusion:Patients with SpA have an increased IR compared to controls. SpA disease-related data like disease duration and HLA-B27 are independently associated with β-cell dysfunction.Disclosure of Interests:Juan Carlos Quevedo-Abeledo Speakers bureau: Abbvie, Fernanda Genre: None declared, Javier Rueda-Gotor: None declared, Alfonso Corrales Speakers bureau: Abbvie, Vanessa Hernández-Hernández Speakers bureau: Pfizer, Abbvie, MSD, Natalia Fañanas-Rodríguez: None declared, Bernardo Lavín-Gómez: None declared, delgado frias esmeralda Speakers bureau: Pfizer, Abbvie, MSD, Antonia de Vera-González: None declared, Alejandra Delgado-González: None declared, Laura de Armas-Rillo: None declared, Maria Teresa García-Unzueta: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Iván Ferraz-Amaro Grant/research support from: Pfizer, Abbvie, Speakers bureau: Pfizer, Abbvie, MSD.

Differential Loss of β-cell Function in Youth vs. Adults Following Treatment Withdrawal in the Restoring Insulin Secretion (RISE) Study

2021 ◽  
pp. 108948
Author(s):  
Kristina M. Utzschneider ◽  
Mark T. Tripputi ◽  
Alexandra Kozedub ◽  
Elena Barengolts ◽  
Sonia Caprio ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Treatment Withdrawal ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Functional Role of Serotonin in Insulin Secretion in a Diet-Induced Insulin-Resistant State

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 444-452 ◽  
Author(s):  
Kyuho Kim ◽  
Chang-Myung Oh ◽  
Mica Ohara-Imaizumi ◽  
Sangkyu Park ◽  
Jun Namkung ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Cell Function ◽  
Β Cell ◽  
Pancreas Perfusion ◽  
Insulin Resistant ◽  
Β Cell Function ◽  
Resistant State ◽  
Insulin Resistant State

The physiological role of serotonin, or 5-hydroxytryptamine (5-HT), in pancreatic β-cell function was previously elucidated using a pregnant mouse model. During pregnancy, 5-HT increases β-cell proliferation and glucose-stimulated insulin secretion (GSIS) through the Gαq-coupled 5-HT2b receptor (Htr2b) and the 5-HT3 receptor (Htr3), a ligand-gated cation channel, respectively. However, the role of 5-HT in β-cell function in an insulin-resistant state has yet to be elucidated. Here, we characterized the metabolic phenotypes of β-cell-specific Htr2b−/− (Htr2b βKO), Htr3a−/− (Htr3a knock-out [KO]), and β-cell-specific tryptophan hydroxylase 1 (Tph1)−/− (Tph1 βKO) mice on a high-fat diet (HFD). Htr2b βKO, Htr3a KO, and Tph1 βKO mice exhibited normal glucose tolerance on a standard chow diet. After 6 weeks on an HFD, beginning at 4 weeks of age, both Htr3a KO and Tph1 βKO mice developed glucose intolerance, but Htr2b βKO mice remained normoglycemic. Pancreas perfusion assays revealed defective first-phase insulin secretion in Htr3a KO mice. GSIS was impaired in islets isolated from HFD-fed Htr3a KO and Tph1 βKO mice, and 5-HT treatment improved insulin secretion from Tph1 βKO islets but not from Htr3a KO islets. Tph1 and Htr3a gene expression in pancreatic islets was not affected by an HFD, and immunostaining could not detect 5-HT in pancreatic islets from mice fed an HFD. Taken together, these results demonstrate that basal 5-HT levels in β-cells play a role in GSIS through Htr3, which becomes more evident in a diet-induced insulin-resistant state.

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.

Full The Relationship between Continuous Glucose Monitoring and OGTT in Youth and Young Adults with Cystic Fibrosis

2021 ◽  
Author(s):  
Christine L Chan ◽  
Laura Pyle ◽  
Tim Vigers ◽  
Philip S Zeitler ◽  
Kristen J Nadeau
Keyword(s):  
Cystic Fibrosis ◽  
Continuous Glucose Monitoring ◽  
Cell Function ◽  
Glucose Monitoring ◽  
Oral Glucose ◽  
Β Cell ◽  
Oral Glucose Tolerance Testing ◽  
C Peptide ◽  
Β Cell Function ◽  
The Relationship

Abstract Context Early glucose abnormalities in people with CF (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized. Objective(s) 1) To determine the relationship between CGM and common OGTT-derived estimates of β-cell function, including C-peptide index and oral disposition index (oDI) and 2) to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis related diabetes (CFRD). Study Design/Methods PwCF not on insulin and healthy controls ages 6-25 yrs were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently-sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson’s correlation coefficient was used to test the association between select CGM and fsOGTT measures. ROC analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD. Results A total of 120 participants (controls=35, CF=85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r=-0.45, p&lt;0.001) and oDIcpeptide (C-peptide index)(1/cpep0) (r=-0.48, p&lt;0.0001). In PwCF, CGM variables had ROC-AUCs ranging from 0.43-0.57 for prediabetes and 0.47-0.6 for CFRD. Conclusions Greater glycemic variability on CGM correlated with reduced β-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically-relevant non-glycemic outcomes in PwCF.

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