The presence of the 1068 G>A variant of P2X7 receptors is associated to an increase in IL-1Ra levels, insulin secretion and pancreatic β-cell function but not with glycemic control in type 2 diabetes patients

Gene ◽  
2018 ◽  
Vol 652 ◽  
pp. 1-6 ◽  
Author(s):  
Edith Elena Uresti-Rivera ◽  
Rocío Edith García-Jacobo ◽  
José Alfredo Méndez-Cabañas ◽  
Laura Elizabeth Gaytan-Medina ◽  
Nancy Cortez-Espinosa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glycemic Control ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
P2x7 Receptors ◽  
Β Cell Function ◽  
Diabetes Patients

Lipid-induced pancreatic β-cell dysfunction: focus on in vivo studies

2011 ◽  
Vol 300 (2) ◽  
pp. E255-E262 ◽  
Author(s):  
Adria Giacca ◽  
Changting Xiao ◽  
Andrei I. Oprescu ◽  
Andre C. Carpentier ◽  
Gary F. Lewis
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Β Cell Function

The phenomenon of lipid-induced pancreatic β-cell dysfunction (“lipotoxicity”) has been very well documented in numerous in vitro experimental systems and has become widely accepted. In vivo demonstration of β-cell lipotoxicity, on the other hand, has not been consistently demonstrated, and there remains a lack of consensus regarding the in vivo effects of chronically elevated free fatty acids (FFA) on β-cell function. Much of the disagreement relates to how insulin secretion is quantified in vivo and in particular whether insulin secretion is assessed in relation to whole body insulin sensitivity, which is clearly reduced by elevated FFA. By correcting for changes in in vivo insulin sensitivity, we and others have shown that prolonged elevation of FFA impairs β-cell secretory function. Prediabetic animal models and humans with a positive family history of type 2 diabetes are more susceptible to this impairment, whereas those with severe impairment of β-cell function (such as individuals with type 2 diabetes) demonstrate no additional impairment of β-cell function when FFA are experimentally raised. Glucolipotoxicity (i.e., the combined β-cell toxicity of elevated glucose and FFA) has been amply demonstrated in vitro and in some animal studies but not in humans, perhaps because there are limitations in experimentally raising plasma glucose to sufficiently high levels for prolonged periods of time. We and others have shown that therapies directed toward diminishing oxidative stress and ER stress have the potential to reduce lipid-induced β-cell dysfunction in animals and humans. In conclusion, lipid-induced pancreatic β-cell dysfunction is likely to be one contributor to the complex array of genetic and metabolic insults that result in the relentless decline in pancreatic β-cell function in those destined to develop type 2 diabetes, and mechanisms involved in this lipotoxicity are promising therapeutic targets.

scholarly journals Glutamate dehydrogenase, insulin secretion, and type 2 diabetes: a new means to protect the pancreatic β-cell?

2012 ◽  
Vol 212 (3) ◽  
pp. 239-242 ◽  
Author(s):  
Isabel Göhring ◽  
Hindrik Mulder
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Carboxylic Acid ◽  
Glutamate Dehydrogenase ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Novel Treatment ◽  
Β Cell Function

In this issue of Journal of Endocrinology, Dr Han and colleagues report a protective effect of the glutamate dehydrogenase activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) under diabetes-like conditions that impair β-cell function in both a pancreatic β-cell line and db/db mice. Based on these observations, the authors suggest that BCH could serve as a novel treatment modality in type 2 diabetes. The present commentary discusses the importance of the findings. Some additional questions are raised, which may be addressed in future investigations, as there is some concern regarding the BCH treatment of β-cell failure.

Nutrient regulation of pancreatic β-cell function in diabetes: problems and potential solutions

2006 ◽  
Vol 34 (5) ◽  
pp. 774-778 ◽  
Author(s):  
P.R. Flatt ◽  
B.D. Green
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Intestinal Hormones ◽  
Nutrient Regulation ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1

Increasing prevalence of obesity combined with longevity will produce an epidemic of Type 2 (non-insulin-dependent) diabetes in the next 20 years. This disease is associated with defects in insulin secretion, specifically abnormalities of insulin secretory kinetics and pancreatic β-cell glucose responsiveness. Mechanisms underlying β-cell dysfunction include glucose toxicity, lipotoxicity and β-cell hyperactivity. Defects at various sites in β-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent studies highlight diverse β-cell actions of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These intestinal hormones target the β-cell to stimulate glucose-dependent insulin secretion through activation of protein kinase A and associated pathways. Both increase gene expression and proinsulin biosynthesis, protect against apoptosis and stimulate replication/neogenesis of β-cells. Incretin hormones therefore represent an exciting future multi-action solution to correct β-cell defect in Type 2 diabetes.

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.

Circulating miR‐146a, miR‐34a and miR‐375 in type 2 diabetes patients, pre‐diabetic and normal‐glycaemic individuals in relation to β‐cell function, insulin resistance and metabolic parameters

2019 ◽  
Vol 46 (12) ◽  
pp. 1092-1100 ◽  
Author(s):  
Rocío E. García‐Jacobo ◽  
Edith E. Uresti‐Rivera ◽  
Diana P. Portales‐Pérez ◽  
Roberto González‐Amaro ◽  
Edgar E. Lara‐Ramírez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cell Function ◽  
Metabolic Parameters ◽  
Β Cell ◽  
Β Cell Function ◽  
Diabetes Patients
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