scholarly journals Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic β-cell area

2010 ◽  
Vol 163 (4) ◽  
pp. 551-558 ◽  
Author(s):  
Thomas G K Breuer ◽  
Bjoern A Menge ◽  
Matthias Banasch ◽  
Waldemar Uhl ◽  
Andrea Tannapfel ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Intrinsic Defect ◽  
Model Assessment ◽  
Inverse Association ◽  
Cell Area ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Secondary Diabetes ◽  
Β Cell Function

IntroductionHyperproinsulinaemia has been reported in patients with type 2 diabetes. It is unclear whether this is due to an intrinsic defect in β-cell function or secondary to the increased demand on the β-cells. We investigated whether hyperproinsulinaemia is also present in patients with secondary diabetes, and whether proinsulin levels are associated with impaired β-cell area or function.Patients and methodsThirty-three patients with and without diabetes secondary to pancreatic diseases were studied prior to pancreatic surgery. Intact and total proinsulin levels were compared with the pancreatic β-cell area and measures of insulin secretion and action.ResultsFasting concentrations of total and intact proinsulin were similar in patients with normal, impaired (including two cases of impaired fasting glucose) and diabetic glucose tolerance (P=0.58 andP=0.98 respectively). There were no differences in the total proinsulin/insulin or intact proinsulin/insulin ratio between the groups (P=0.23 andP=0.71 respectively). There was a weak inverse association between the total proinsulin/insulin ratio and pancreatic β-cell area (r2=0.14,P=0.032), whereas the intact proinsulin/insulin ratio and the intact and total proinsulin levels were unrelated to β-cell area. However, a strong inverse relationship between homeostasis model assessment index of β-cell function and both the total and the intact proinsulin/insulin ratio was found (r2=0.55 andr2=0.48 respectively). The association of insulin resistance (IR) with intact proinsulin was much weaker than the correlation with fasting insulin.ConclusionsHyperproinsulinaemia is associated with defects in insulin secretion rather than a reduction in β-cell area. The weak association between intact proinsulin and IR argues against the usefulness of this parameter in clinical practice.

scholarly journals Estimates of Insulin Secretory Function in Apparently Healthy Volunteers Vary as a Function of How the Relevant Variables Are Quantified

2011 ◽  
Vol 57 (4) ◽  
pp. 627-632 ◽  
Author(s):  
Barry R Johns ◽  
Fahim Abbasi ◽  
Gerald M Reaven
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Cell Function ◽  
Model Assessment ◽  
Pancreatic Β Cell ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Β Cell Function

BACKGROUND Several surrogate estimates have been used to define relationships between insulin action and pancreatic β-cell function in healthy individuals. Because it is unclear how conclusions about insulin secretory function depend on specific estimates used, we evaluated the effect of different approaches to measurement of insulin action and secretion on observations of pancreatic β-cell function in individuals whose fasting plasma glucose (FPG) was <7.0 mmol/L (126 mg/dL). METHODS We determined 2 indices of insulin secretion [homeostasis model assessment of β-cell function (HOMA-β) and daylong insulin response to mixed meals], insulin action [homeostasis model assessment of insulin resistance (HOMA-IR) and steady-state plasma glucose (SSPG) concentration during the insulin suppression test], and degree of glycemia [fasting plasma glucose (FPG) and daylong glucose response to mixed meals] in 285 individuals with FPG <7.0 mmol/L. We compared the relationship between the 2 measures of insulin secretion as a function of the measures of insulin action and degree of glycemia. RESULTS Assessment of insulin secretion varied dramatically as a function of which of the 2 methods was used and which measure of insulin resistance or glycemia served as the independent variable. For example, the correlation between insulin secretion (HOMA-β) and insulin resistance varied from an r value of 0.74 (when HOMA-IR was used) to 0.22 (when SSPG concentration was used). CONCLUSIONS Conclusions about β-cell function in nondiabetic individuals depend on the measurements used to assess insulin action and insulin secretion. Viewing estimates of insulin secretion in relationship to measures of insulin resistance and/or degree of glycemia does not mean that an unequivocal measure of pancreatic β-cell function has been obtained.

scholarly journals Impaired Pancreatic β-Cell Function in Critically Ill Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Shereen A. Mohamed ◽  
Nora E. Badawi ◽  
Hoiyda A. AbdelRasol ◽  
Hossam M. AbdelAziz ◽  
Nirvana A. Khalaf ◽  
...  
Keyword(s):  
Cell Function ◽  
Multivariate Logistic Regression Analysis ◽  
Pediatric Intensive Care ◽  
Glucose Production ◽  
Critically Ill Children ◽  
Model Assessment ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Β Cell Function

Critical illness hyperglycemia (CIH) is common in the pediatric intensive care unit (PICU). Increased glucose production, insulin resistance (IR), and pancreatic β-cell dysfunction are responsible mechanisms. We aimed to investigate β-cell function in the PICU and to uncover its relation to clinical and laboratory variables and ICU mortality. We prospectively recruited 91 children. Pancreatic β-cell function was assessed by using a homeostasis model assessment (HOMA)-β. Patients with β-cell function <40.0% had significantly higher Pediatric Risk of Mortality III (PRISM III) scores, higher rates of a positive C-reactive protein (CRP), lower IR, and a longer hospital stay. The patients with 40–80% β-cell function had the highest IR. Intermediate IR was found when the β-cell function was >80%. ICU survivors had better β-cell function than ICU non-survivors. A multivariate logistic regression analysis revealed that higher PRISM III score and HOMA-β <80.0% were significant predictors of mortality. In conclusion, β-cell dysfunction is prevalent among PICU patients and influences patient morbidity and mortality.

Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children

2019 ◽  
Vol 74 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Ting Chen ◽  
Fengyun Wang ◽  
Zhenyu Chu ◽  
Ling Sun ◽  
Haitao Lv ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Pancreatic Β Cell ◽  
Obese Children ◽  
Β Cell ◽  
Β Cell Function ◽  
Obese Subjects

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.

scholarly journals Bioactive Phytochemicals Isolated from Akebia quinata Enhances Glucose-Stimulated Insulin Secretion by Inducing PDX-1

Plants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1087
Author(s):  
Dahae Lee ◽  
Jin Su Lee ◽  
Jurdas Sezirahiga ◽  
Hak Cheol Kwon ◽  
Dae Sik Jang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Experimental Studies ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Etoh Extract ◽  
Chemical Structures ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion ◽  
Phosphoinositide 3 Kinase

Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-β-d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1–7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1–7 on insulin secretion using the INS-1 rat pancreatic β-cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic β-cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-β-d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic β-cell survival and function. Moreover, isolate 1 markedly induced the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), and Akt, which regulate the transcription of PDX-1. The results of our experimental studies indicated that stigmasterol-3-O-β-d-glucoside (1) isolated from the fruits of A. quinata can potentially enhance insulin secretion, and might alleviate the reduction in GSIS during the development of T2DM.

scholarly journals Transcellular Neuroligin-2 Interactions Enhance Insulin Secretion and Are Integral to Pancreatic β Cell Function

2012 ◽  
Vol 287 (24) ◽  
pp. 19816-19826 ◽  
Author(s):  
Arthur T. Suckow ◽  
Charles Zhang ◽  
Sonya Egodage ◽  
Davide Comoletti ◽  
Palmer Taylor ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Maturation of pancreatic β-cell function in the fetal horse during late gestation

2005 ◽  
Vol 186 (3) ◽  
pp. 467-473 ◽  
Author(s):  
A L Fowden ◽  
D S Gardner ◽  
J C Ousey ◽  
D A Giussani ◽  
A J Forhead
Keyword(s):  
Insulin Secretion ◽  
Cell Response ◽  
Endocrine Pancreas ◽  
Cell Function ◽  
Late Gestation ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Glucose Administration ◽  
Β Cell Function ◽  
Cortisol Levels

At birth, the endocrine pancreas becomes more directly involved in the control of glycaemia than in utero. However, compared with other tissues, relatively little is known about the maturational changes that occur in the fetal endocrine pancreas in preparation for extrauterine life. This study examined the pancreatic β-cell response to exogenous administration of glucose and arginine in fetal horses with respect to their gestational age and concentration of cortisol, the hormone responsible for prepartum maturation of other fetal tissues. Glucose administration had no effect on fetal insulin secretion between 175 and 230 days of gestation but evoked a rapid insulin response in fetuses closer to term (290–327 days). In late gestation, the β-cell response was more rapid and greater in magnitude in fetuses with basal cortisol levels higher than 15 ng/ml than in those with lower cortisol values at the time of glucose administration. The fetal β-cell response to arginine was unaffected by the rise in fetal plasma cortisol towards term. These findings show that there are maturational changes in pancreatic β-cell function in fetal horses as cortisol levels rise close to term. Primarily, these prepartum maturational changes were in the mechanisms of glucose-stimulated insulin secretion, which would enable the β cells to regulate glycaemia at the higher glucose levels observed postnatally.

scholarly journals Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity

2014 ◽  
Vol 223 (2) ◽  
pp. 107-117 ◽  
Author(s):  
Michael Rouse ◽  
Antoine Younès ◽  
Josephine M Egan
Keyword(s):  
Insulin Secretion ◽  
Cell Lines ◽  
Cell Function ◽  
Human Islets ◽  
Dependent Manner ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pde Inhibitors ◽  
Β Cell Function

Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against β-cell dysfunction, we studied their mechanism(s) of action in β-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic β-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic β-cells. In our current study, we found that both RES (0.1–10 μmol/l) and CUR (1–100 pmol/l)-regulated insulin secretion under glucose-stimulated conditions. Additionally, treating β-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in β-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic β-cell function.

scholarly journals Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixuan Liu ◽  
Tao Yuan ◽  
Shuoning Song ◽  
Shi Chen ◽  
Linjie Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Literature Review ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Klinefelter Syndrome ◽  
Oral Glucose ◽  
Model Assessment ◽  
Β Cell ◽  
Β Cell Function

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

scholarly journals Oxytocin signal contributes to the adaptative growth of islets during gestation

2021 ◽  
Author(s):  
Ping Gu ◽  
Yuege Lin ◽  
Qi Wan ◽  
Dongming Su ◽  
Qun Shu
Keyword(s):  
Insulin Secretion ◽  
Pregnant Women ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Cell Adaptation ◽  
Β Cell Function ◽  
Insulinoma Cells

Background: Increased insulin production and secretion by pancreatic β-cells are important for ensuring the high insulin demand during gestation. However, the underlying mechanism of β-cell adaptation during gestation or in gestational diabetes mellitus (GDM) remains unclear. Oxytocin is an important physiological hormone in gestation and delivery, and it also contributes to the maintenance of β-cell function. The aim of this study was to investigate the role of oxytocin in β-cell adaptation during pregnancy. Methods: The relationship between the blood oxytocin level and pancreatic β-cell function in patients with GDM and healthy pregnant women was investigated. Gestating and non-gestating mice were used to evaluate the in vivo effect of oxytocin signal on β-cells during pregnancy. In vitro experiments were performed on INS-1 insulinoma cells. Results: The blood oxytocin levels were lower in patients with GDM than in healthy pregnant women and were associated with impaired pancreatic β-cell function. Acute administration of oxytocin increased insulin secretion in both gestating and non-gestating mice. A three-week oxytocin treatment promoted the proliferation of pancreatic β-cells and increased the β-cell mass in gestating but not non-gestating mice. Antagonism of oxytocin receptors by atosiban impaired insulin secretion and induced GDM in gestating but not non-gestating mice. Oxytocin enhanced glucose-stimulated insulin secretion, activated the mitogen-activated protein kinase pathway, and promoted cell proliferation in INS-1 cells. Conclusions: These findings provide strong evidence that oxytocin is needed for β-cell adaptation during pregnancy to maintain β-cell function, and lack of oxytocin could be associated with the risk of GDM.

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