scholarly journals Isletβ-Cell Mass Preservation and Regeneration in Diabetes Mellitus: Four Factors with Potential Therapeutic Interest

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jose Manuel Mellado-Gil ◽  
Nadia Cobo-Vuilleumier ◽  
Benoit R. Gauthier
Keyword(s):  
Diabetes Mellitus ◽  
Islet Cells ◽  
Cell Mass ◽  
Cell Types ◽  
Diabetic Patients ◽  
Cell Protection ◽  
Pancreatic Cell ◽  
Cell Replacement ◽  
Alternative Sources ◽  
And Function

Isletβ-cell replacement and regeneration are two promising approaches for the treatment of Type 1 Diabetes Mellitus. Indeed, the success of islet transplantation in normalizing blood glucose in diabetic patients has provided the proof of principle that cell replacement can be employed as a safe and efficacious treatment. Nonetheless, shortage of organ donors has hampered expansion of this approach. Alternative sources of insulin-producing cells are mandatory to fill this gap. Although great advances have been achieved in generating surrogateβ-cells from stem cells, current protocols have yet to produce functionally mature insulin-secreting cells. Recently, the concept of islet regeneration in which newβ-cells are formed from either residualβ-cell proliferation or transdifferentiation of other endocrine islet cells has gained much interest as an attractive therapeutic alternative to restoreβ-cell mass. Complementary approaches to cell replacement and regeneration could aim at enhancingβ-cell survival and function. Herein, we discuss the value of Hepatocyte Growth Factor (HGF), Glucose-Dependent Insulinotropic Peptide (GIP), Paired box gene 4 (Pax4) and Liver Receptor Homolog-1 (LRH-1) as key players forβ-cell replacement and regeneration therapies. These factors conveyβ-cell protection and enhanced function as well as facilitating proliferation and transdifferentiation of other pancreatic cell types toβ-cells, under stressful conditions.

Cellular plasticity of the pancreas

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Luc Baeyens ◽  
Luc Bouwens
Keyword(s):  
Diabetes Mellitus ◽  
Cell Differentiation ◽  
Cell Types ◽  
Β Cells ◽  
Cell Replacement Therapy ◽  
Β Cell ◽  
Pancreatic Cell ◽  
Cell Replacement

Abstract Cell replacement therapy holds promises for treatment of patients suffering from diabetes mellitus. When determining the appropriate strategies to amplify the amount of transplantable β-cells, sufficient knowledge of the developmental programs regulating β-cell differentiation is crucial. Here, we describe the plasticity of the different pancreatic cell types in vivo and in vitro and their potential to serve as β-cell progenitor.

scholarly journals In Vivo Role of Focal Adhesion Kinase in Regulating Pancreatic  -Cell Mass and Function Through Insulin Signaling, Actin Dynamics, and Granule Trafficking

Diabetes ◽  
2012 ◽  
Vol 61 (7) ◽  
pp. 1708-1718 ◽  
Author(s):  
E. P. Cai ◽  
M. Casimir ◽  
S. A. Schroer ◽  
C. T. Luk ◽  
S. Y. Shi ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Insulin Signaling ◽  
Cell Mass ◽  
Actin Dynamics ◽  
Pancreatic Cell ◽  
And Function

Harnessing immune cells to enhance β-cell mass in type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Ercument Dirice ◽  
Rohit N Kulkarni
Keyword(s):  
Type 1 Diabetes ◽  
Mononuclear Cells ◽  
Islet Cells ◽  
Cell Mass ◽  
Cell Loss ◽  
Cell Types ◽  
Β Cells ◽  
Β Cell ◽  
Autoimmune Attack

Type 1 diabetes is characterized by early β-cell loss leading to insulin dependence in virtually all patients with the disease in order to maintain glucose homeostasis. Most studies over the past few decades have focused on limiting the autoimmune attack on the β cells. However, emerging data from patients with long-standing diabetes who continue to harbor functional insulin-producing cells in their diseased pancreas have prompted scientists to examine whether proliferation of existing β cells can be enhanced to promote better glycemic control. In support of this concept, several studies indicate that mononuclear cells that infiltrate the islets have the capacity to trigger proliferation of islet cells including β cells. These observations indicate the exciting possibility of identifying those mononuclear cell types and their soluble factors and harnessing their ability to promote β-cell growth concomitant with autoimmune therapy to prevent the onset and/or halt the progression of the disease.

scholarly journals Melatonin Ameliorates MI-Induced Cardiac Remodeling and Apoptosis through a JNK/p53-Dependent Mechanism in Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Linhe Lu ◽  
Jipeng Ma ◽  
Mingming Sun ◽  
Xiaowu Wang ◽  
Erhe Gao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Interstitial Fibrosis ◽  
Myocardial Dysfunction ◽  
Cardiac Injury ◽  
Diabetic Patients ◽  
High Fat ◽  
Adult Mice ◽  
Cardiac Geometry ◽  
And Function

Diabetes mellitus, a worldwide health threat, is considered an independent risk factor for cardiovascular diseases. The overall cardiovascular risk of diabetes is similar to the one having one myocardial infarction (MI) attack although the precise impact of diabetes on MI-induced myocardial anomalies remains elusive. Given that mortality following MI is much greater in diabetic patients compared to nondiabetic patients, this study was designed to examine the effect of melatonin on MI injury-induced myocardial dysfunction in diabetes. Adult mice were made diabetic using high-fat feeding and streptozotocin (100 mg/kg body weight) prior to MI and were treated with melatonin (50 mg/kg/d, p.o.) for 4 weeks prior to assessment of cardiac geometry and function. The MI procedure in diabetes displayed overt changes in cardiac geometry (chamber dilation and interstitial fibrosis) and functional anomalies (reduced fractional shortening and cardiomyocyte contractile capacity) in association with elevated c-Jun N-terminal kinase (JNK) phosphorylation and p53 level. Melatonin treatment markedly attenuated cardiac dysfunction and myocardial fibrosis in post-MI diabetic mice. Furthermore, melatonin decreased JNK phosphorylation, reduced p53 levels, and suppressed apoptosis in hearts from the post-MI diabetic group. In vitro findings revealed that melatonin effectively counteracted high-glucose/high fat-hypoxia-induced cardiomyocyte apoptosis and contractile dysfunction through a JNK-mediated mechanism, the effects of which were impaired by the JNK activator anisomycin. In summary, our study suggests that melatonin protects against myocardial injury in post-MI mice with diabetes, which offers a new therapeutic strategy for the management of MI-induced cardiac injury in diabetes.

scholarly journals β-Cell Generation: Can Rodent Studies Be Translated to Humans?

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Françoise Carlotti ◽  
Arnaud Zaldumbide ◽  
Johanne H. Ellenbroek ◽  
H. Siebe Spijker ◽  
Rob C. Hoeben ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Mass ◽  
Cell Types ◽  
Organ Donors ◽  
Cell Replacement Therapy ◽  
Β Cell ◽  
Cell Replacement ◽  
Therapeutic Alternatives

β-cell replacement by allogeneic islet transplantation is a promising approach for patients with type 1 diabetes, but the shortage of organ donors requires new sources ofβcells. Islet regenerationin vivoand generation ofβ-cellsex vivofollowed by transplantation represent attractive therapeutic alternatives to restore theβ-cell mass. In this paper, we discuss different postnatal cell types that have been envisaged as potential sources for futureβ-cell replacement therapy. The ultimate goal being translation to the clinic, a particular attention is given to the discrepancies between findings from studies performed in rodents (bothex vivoon primary cells andin vivoon animal models), when compared with clinical data and studies performed on human cells.

scholarly journals Development of islet organoids from human induced pluripotent stem cells in a cross-linked collagen scaffold

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shruti Sandilya ◽  
Shashi Singh
Keyword(s):  
Pluripotent Stem Cells ◽  
Islet Cells ◽  
Collagen Scaffold ◽  
Marker Genes ◽  
Cell Replacement Therapy ◽  
Glucose Stimulation ◽  
Cell Replacement ◽  
Pancreatic Progenitors ◽  
Induced Pluripotent ◽  
And Function

AbstractIslets organoids would have value in the cell replacement therapy for diabetes apart from usual personalized drug screening routes. Generation of a large number of Islets like clusters, with ability to respond to glucose stimulation appears to be an ideal choice. In this study we have generated islet organoids with the ability to respond to glucose stimulation by insulin release. The source of the cells was an iPSC cell line differentiated into the pancreatic progenitors. These cells were assembled in matrigel or cross-linked collagen scaffold and compared for their efficacy to release insulin upon stimulation with glucose. The assembled organoids were examined by immunohistochemistry and expression of the relevant marker genes. The organoids showed expression of islet like markers in both - matrigel and crosslinked collagen scaffold. The islet organoids in both the cases showed release of insulin upon stimulation with glucose. The crosslinked collagen scaffold is quite stable and supports islet cells growth and function.

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.

Microparticles as new markers of cardiovascular risk in diabetes and beyond

2016 ◽  
Vol 116 (08) ◽  
pp. 220-234 ◽  
Author(s):  
Francesca Santilli ◽  
Marco Marchisio ◽  
Paola Lanuti ◽  
Andrea Boccatonda ◽  
Sebastiano Miscia ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Risk ◽  
Atherosclerotic Plaque ◽  
Metabolic Diseases ◽  
Vascular Diseases ◽  
Cell Types ◽  
Diabetic Patients ◽  
Wide Range ◽  
Relevant Role ◽  
Polychromatic Flow Cytometry

SummaryThe term microparticle (MP) identifies a heterogeneous population of vesicles playing a relevant role in the pathogenesis of vascular diseases, cancer and metabolic diseases such as diabetes mellitus. MPs are released by virtually all cell types by shedding during cell growth, proliferation, activation, apoptosis or senescence processes. MPs, in particular platelet- and endothelial-derived MPs (PMPs and EMPs), are increased in a wide range of thrombotic disorders, with an interesting relationship between their levels and disease pathophysiology, activity or progression. EMP plasma levels have been associated with several cardiovascular diseases and risk factors. PMPs are also shown to be involved in the progressive formation of atherosclerotic plaque and development of arterial thrombosis, especially in diabetic patients. Indeed, diabetes is characterised by an increased procoagulant state and by a hyperreactive platelet phenotype, with enhanced adhesion, aggregation, and activation. Elevated MP levels, such as TF+ MPs, have been shown to be one of the procoagulant determinants in patients with type 2 diabetes mellitus. Atherosclerotic plaque constitutes an opulent source of sequestered MPs, called “plaque” MPs. Otherwise, circulating MPs represent a TF reservoir, named “blood-borne” TF, challenging the dogma that TF is a constitutive protein expressed in minute amounts. “Blood-borne” TF is mainly harboured by PMPs, and it can be trapped within the developing thrombus. MP detection and enumeration by polychromatic flow cytometry (PFC) have opened interesting perspectives in clinical settings, particularly for the evaluation of MP numbers and phenotypes as independent marker of cardiovascular risk, disease and outcome in diabetic patients.

Could lncRNAs contribute to β-cell identity and its loss in Type 2 diabetes?

2013 ◽  
Vol 41 (3) ◽  
pp. 797-801 ◽  
Author(s):  
Timothy J. Pullen ◽  
Guy A. Rutter
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Cell Types ◽  
Human Populations ◽  
Β Cell ◽  
Cell Identity ◽  
Genome Wide ◽  
And Function

The progression of Type 2 diabetes is accompanied by diminishing islet β-cell mass and function. It has been proposed that β-cells are lost not only through apoptosis, but also by dedifferentiating into progenitor-like cells. There is therefore much interest in the mechanisms which define and maintain β-cell identity. The advent of genome-wide analyses of chromatin modifications has highlighted the role of epigenetic factors in determining cell identity. There is also evidence from both human populations and animal models for an epigenetic component in susceptibility to Type 2 diabetes. The mechanisms responsible for defining the epigenetic landscape in individual cell types are poorly understood, but there is growing evidence of a role for lncRNAs (long non-coding RNAs) in this process. In the present paper, we discuss some of the mechanisms through which lncRNAs may contribute to β-cell identity and Type 2 diabetes risk.

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