scholarly journals Role of Ink4a/Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Elisabet Salas ◽  
Nabil Rabhi ◽  
Philippe Froguel ◽  
Jean-Sébastien Annicotte
Keyword(s):  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Primary Source ◽  
Tumour Suppressor Genes ◽  
General View ◽  
Diabetes Research ◽  
And Function ◽  
Cdkn2a Locus

The ARF/INK4A (Cdkn2a) locus includes the linked tumour suppressor genes p16INK4a and p14ARF (p19ARF in mice) that trigger the antiproliferative activities of both RB and p53. With beta cell self-replication being the primary source for new beta cell generation in adult animals, the network by which beta cell replication could be increased to enhance beta cell mass and function is one of the approaches in diabetes research. In this review, we show a general view of the regulation points at transcriptional and posttranslational levels of Cdkn2a locus. We describe the molecular pathways and functions of Cdkn2a in beta cell cycle regulation. Given that aging reveals increased p16Ink4a levels in the pancreas that inhibit the proliferation of beta cells and decrease their ability to respond to injury, we show the state of the art about the role of this locus in beta cell senescence and diabetes development. Additionally, we focus on two approaches in beta cell regeneration strategies that rely on Cdkn2a locus negative regulation: long noncoding RNAs and betatrophin.

scholarly journals Role of MicroRNAs in Islet Beta-Cell Compensation and Failure during Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Valérie Plaisance ◽  
Gérard Waeber ◽  
Romano Regazzi ◽  
Amar Abderrahmani
Keyword(s):  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Oxidized Ldl ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Proliferation ◽  
Beta Cell Compensation ◽  
And Function

Pancreatic beta-cell function and mass are markedly adaptive to compensate for the changes in insulin requirement observed during several situations such as pregnancy, obesity, glucocorticoids excess, or administration. This requires a beta-cell compensation which is achieved through a gain of beta-cell mass and function. Elucidating the physiological mechanisms that promote functional beta-cell mass expansion and that protect cells against death, is a key therapeutic target for diabetes. In this respect, several recent studies have emphasized the instrumental role of microRNAs in the control of beta-cell function. MicroRNAs are negative regulators of gene expression, and are pivotal for the control of beta-cell proliferation, function, and survival. On the one hand, changes in specific microRNA levels have been associated with beta-cell compensation and are triggered by hormones or bioactive peptides that promote beta-cell survival and function. Conversely, modifications in the expression of other specific microRNAs contribute to beta-cell dysfunction and death elicited by diabetogenic factors including, cytokines, chronic hyperlipidemia, hyperglycemia, and oxidized LDL. This review underlines the importance of targeting the microRNA network for future innovative therapies aiming at preventing the beta-cell decline in diabetes.

scholarly journals Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice

2016 ◽  
Vol 291 (28) ◽  
pp. 14695-14705 ◽  
Author(s):  
Yun-Zi Liu ◽  
Xiaoyun Cheng ◽  
Ting Zhang ◽  
Sojin Lee ◽  
Jun Yamauchi ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
And Function

scholarly journals Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 104
Author(s):  
Elisa Fernández-Millán ◽  
Carlos Guillén
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Biology ◽  
Pancreatic Beta Cells ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Short Chain Fatty Acids

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D. In this review, we provide an overview of secreted factors from diverse organs and tissues that have been shown to impact beta-cell biology. Specifically, we discuss experimental and clinical evidence in support for a role of gut to beta-cell crosstalk, paying particular attention to bacteria-derived factors including short-chain fatty acids, lipopolysaccharide, and factors contained within extracellular vesicles that influence the function and/or the survival of beta cells under normal or diabetogenic conditions.

Role of growth factors in control of pancreatic beta cell mass

2014 ◽  
Vol 26 (4) ◽  
pp. 475-479 ◽  
Author(s):  
Lynne L. Levitsky ◽  
Goli Ardestani ◽  
David B. Rhoads
Keyword(s):  
Growth Factors ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Pancreatic Beta Cell Mass

scholarly journals The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker

Diabetologia ◽  
2010 ◽  
Vol 53 (7) ◽  
pp. 1406-1414 ◽  
Author(s):  
J. Altirriba ◽  
R. Gasa ◽  
S. Casas ◽  
M. J. Ramírez-Bajo ◽  
S. Ros ◽  
...  
Keyword(s):  
Beta Cell ◽  
Transmembrane Protein ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Islet Physiology ◽  
Potential Use

scholarly journals Near Infrared Optical Projection Tomography for Assessments of β-cell Mass Distribution in Diabetes Research

10.3791/50238 ◽  
2013 ◽  
Author(s):  
Anna U Eriksson ◽  
Christoffer Svensson ◽  
Andreas Hörnblad ◽  
Abbas Cheddad ◽  
Elena Kostromina ◽  
...  
Keyword(s):  
Beta Cell ◽  
Mass Distribution ◽  
Near Infrared ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Diabetes Research ◽  
Optical Projection Tomography ◽  
Optical Projection

scholarly journals The Current State of Beta-Cell-Mass PET Imaging for Diabetes Research and Therapies

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1824
Author(s):  
Pierre Cheung ◽  
Olof Eriksson
Keyword(s):  
Positron Emission Tomography ◽  
Beta Cell ◽  
Disease Progression ◽  
Beta Cell Function ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Emission Tomography ◽  
Diabetes Research ◽  
Positron Emission

Diabetes is a chronic metabolic disease affecting over 400 million people worldwide and one of the leading causes of death, especially in developing nations. The disease is characterized by chronic hyperglycemia, caused by defects in the insulin secretion or action pathway. Current diagnostic methods measure metabolic byproducts of the disease such as glucose level, glycated hemoglobin (HbA1c), insulin or C-peptide levels, which are indicators of the beta-cell function. However, they inaccurately reflect the disease progression and provide poor longitudinal information. Beta-cell mass has been suggested as an alternative approach to study disease progression in correlation to beta-cell function, as it behaves differently in the diabetes physiopathology. Study of the beta-cell mass, however, requires highly invasive and potentially harmful procedures such as pancreatic biopsies, making diagnosis and monitoring of the disease tedious. Nuclear medical imaging techniques using radiation emitting tracers have been suggested as strong non-invasive tools for beta-cell mass. A highly sensitive and high-resolution technique, such as positron emission tomography, provides an ideal solution for the visualization of beta-cell mass, which is particularly essential for better characterization of a disease such as diabetes, and for estimating treatment effects towards regeneration of the beta-cell mass. Development of novel, validated biomarkers that are aimed at beta-cell mass imaging are thus highly necessary and would contribute to invaluable breakthroughs in the field of diabetes research and therapies. This review aims to describe the various biomarkers and radioactive probes currently available for positron emission tomography imaging of beta-cell mass, as well as highlight the need for precise quantification and visualization of the beta-cell mass for designing new therapy strategies and monitoring changes in the beta-cell mass during the progression of diabetes.

scholarly journals Verapamil can be used as a Type 2 Diabetes Mellitus Saviour and Stopping the need for Insulin in Uncontrolled Type 2 Diabetes Mellitus

2021 ◽  
pp. 1-8
Author(s):  
Mahmoud Younis ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Interacting Protein ◽  
Significant Difference ◽  
And Function

Introduction: Diabetes mellitus is not just a disease as it is already known, the matter is more complicated, and it is considered as an assembly of metabolic defects with end result of hyperglycemia.verapamil can decrease the expression of thioredoxin-interacting protein (TXNIP), which is recognized as an important factor in pancreatic beta cells.verapamil could enhance beta cell mass and function. Materials and Methods: 160 type 2 diabetes patients in 2 parallel groups. Results: show statistically significant difference in favour of verapamil in increasing c-peptide levels and decreasing hba1c levels. Conclusion: Verapamil could be used as a type 2 diabetes saviour by increasing beta cell mass and function.

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