scholarly journals Mitochondria as a Target for Future Diabetes Treatments

2015 ◽  
Vol 3 (1) ◽  
pp. 45-50
Author(s):  
Franziska Thimm ◽  
Marten Szibor
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Life Support ◽  
Diabetes Management ◽  
Glucagon Secretion ◽  
Treatment Method ◽  
Serial Killer ◽  
Diabetic Patients ◽  
Insulin Resistant ◽  
Islet Transplants

Diabetes mellitus is rapidly becoming the world’s most dangerous serial killer. Type 1 diabetes (T1D) is a currently incurable autoimmune disease marked by progressive, and eventually exhaustive, destruction of the insulin-producing pancreatic beta cells. Type 2 diabetes (T2D) describes the combination of insulin resistance in peripheral tissue, insufficient insulin secretion from the pancreatic beta cells, and excessive glucagon secretion from the pancreatic alpha cells. T1D as well as severe cases of T2D are treated with insulin replacement, which can merely be considered as life support for the acute phases of the disease. Islet replacement of insulin-producing pancreatic beta cells represents a potential treatment method for both insulin-depleted diabetes (T1D) and insulin-resistant diabetes (T2D) and may shift diabetes management from life saving measures to a cure. One of the key challenges in islet transplants is the generation of reactive oxygen species (ROS) and the associated oxidative stress, which restricts graft longevity. A major leak of ROS takes place during oxidative phosphorylation at mitochondrial electron transport chain (ETC). Additionally, hyperglycemia-induced superoxide (O2•-) production has been linked to the development and progression of diabetic complications, both macrovascular and microvascular. Decreasing ROS in diabetic patients may prevent the incidence of long term diabetes complications. This review provides an overview of the role of mitochondria in diabetes, introducing them as a possible target for future treatment of diabetes.

scholarly journals Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients

Diabetologia ◽  
2005 ◽  
Vol 48 (2) ◽  
pp. 282-289 ◽  
Author(s):  
M. Anello ◽  
R. Lupi ◽  
D. Spampinato ◽  
S. Piro ◽  
M. Masini ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Morphological Alterations ◽  
Type 2 Diabetic

scholarly journals Metabolic reprogramming of cytotoxic T lymphocytes by high glucose enhances pancreatic beta cell apoptosis via TRAIL

2021 ◽  
Author(s):  
Wenjuan Yang ◽  
Andreas Denger ◽  
Caroline Diener ◽  
Frederic Kueppers ◽  
Leticia Soriano-Baguet ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Lymphocytes ◽  
Beta Cells ◽  
Cytotoxic T Lymphocytes ◽  
High Glucose ◽  
Pancreatic Beta Cells ◽  
Metabolic Reprogramming ◽  
Diabetic Patients ◽  
Beta Cell Apoptosis ◽  
The Impact

Cytotoxic T lymphocytes (CTLs) are involved in development of diabetes. However, the impact of excessive glucose on CTL effector functions remains largely elusive. Here, we report that metabolic processes in CTLs are reprogrammed by high glucose (HG). TNF-related apoptosis inducing ligand (TRAIL) is substantially up-regulated in CTLs in environments with HG both in vitro and in vivo in a diabetic mouse model and in diabetic patients. The PI3K-Akt-NFκB axis and non-mitochondrial reactive oxygen species (ROS) are both involved in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of insulin-producing beta cells. Metformin and Vitamin D synergistically reduce HG-enhanced expression of TRAIL in CTLs and coherently protect beta cells from TRAIL-mediated apoptosis. Our work not only reveals a novel mechanism of CTL involvement in progression of diabetes, but also establishes CTLs as a target for combined metformin and vitamin D therapy to protect pancreatic beta cells of diabetic patients.

scholarly journals Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette–Guérin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity

2020 ◽  
Author(s):  
Bassam M. Ayoub ◽  
Eman Ramadan ◽  
Nermeen Ashoush ◽  
Mariam M. Tadros ◽  
Moataz S. Hendy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Study ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Aerobic Glycolysis ◽  
Bcg Vaccine ◽  
Diabetic Patients ◽  
Bcg Vaccination ◽  
Significant Difference

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose levels. Diabetic patient’s mortality rates with COVID-19 are higher than cardiovascular or cancer patients. Recently Bacillus Calmette–Guérin (BCG) has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to Beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from TB and leprosy and has been repositioned for treatment of bladder cancer, diabetes & multiple sclerosis. Recently, the COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 & diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide & PCPRI laboratory findings after BCG vaccination for a 9 years’ patient. The patient was re-vaccinated based on a negative tuberculin test & no scar at the site of injection of the 1st BCG vaccination at birth. Furthermore, the authors in the present article described a prospective BCG multi-dose clinical study in full details that they will apply in case of acceptance of their submitted grant & the ethical committee approval. The aim of the clinical study is to check if double dose BCG (4 weeks apart) will show a significant difference in the protection of health care professionals in Egypt. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions & exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.

Cerium and Yttrium Oxide Nanoparticles and Nano-selenium Produce Protective Effects Against H2O2-induced Oxidative Stress in Pancreatic Beta Cells by Modulating Mitochondrial Dysfunction

2020 ◽  
Vol 8 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Shima Tavoosi ◽  
Amir Hossein Baghsheikhi ◽  
Seyed Vahid Shetab-Boushehri ◽  
Mona Navaei-Nigjeh ◽  
Nazanin Namazi Sarvestani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Beta Cell ◽  
Mitochondrial Dysfunction ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucagon Secretion ◽  
Oxide Nanoparticles ◽  
Beta Cell Line ◽  
Yttrium Oxide Nanoparticles

Background: Type 1 diabetes mellitus is characterized by the destruction of insulin- producing Beta cells in the pancreas. Researchers hope that islet transplantation will help to patients with insulin-dependent diabetes mellitus (IDDM). Oxidative stress is the most important challenge that beta cells face to it after isolation, and mitochondrial dysfunction is a crucial mediator in beta cells death. Hence, therapeutic approaches can shift to antioxidants through the application of nanoparticles such as cerium and yttrium oxide nanoparticles (Cer and Ytt Ox NPs) and nano-selenium (Nan Se). Objectives: This study evaluates the effects of Cer and Ytt Ox NPs and Nan Se on H2O2- induced oxidative stress in pancreatic beta cells with focus on mitochondrial dysfunction pathway. Methods: CRI-D2 beta-cell line were pretreated with Cer Ox NPs (200 µM) + Ytt Ox NPs (0.5 µg/mL) for 3 days and/or Nan Se (0.01 µM) for 1 day. Then markers of oxidative stress, mitochondrial dysfunction, insulin and glucagon secretion were measured. Results: We reported a decrease in H2O2-induced reactive oxygen species (ROS) level and glucagon secretion, and an increase in H2O2-reduced ATP/ADP ratio, MMP, as well as UCP2 protein expression, and insulin secretion by pretreatment of CRI-D2 cells with Cer and Ytt Ox NPs and/or Nan Se. Conclusion: We found maximum protective effect with Cer and Ytt Ox NPs on CRI-D2 beta-cell line exposed by H2O2 for keeping beta cells alive until transplant whereas combination of Cer and Ytt Ox NPs and Nan Se had very little protective effect in this condition.

scholarly journals Structural and functional polarisation of human pancreatic beta cells in islets from organ donors with and without type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Louise Cottle ◽  
Wan Jun Gan ◽  
Ian Gilroy ◽  
Jaswinder S. Samra ◽  
Anthony J. Gill ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cultured Cells ◽  
Human Islets ◽  
Scaffold Proteins ◽  
Diabetic Patients ◽  
Human Pancreas ◽  
Insulin Granule

Abstract Aims/hypothesis We hypothesised that human beta cells are structurally and functional polarised with respect to the islet capillaries. We set out to test this using confocal microscopy to map the 3D spatial arrangement of key proteins and live-cell imaging to determine the distribution of insulin granule fusion around the cells. Methods Human pancreas samples were rapidly fixed and processed using the pancreatic slice technique, which maintains islet structure and architecture. Slices were stained using immunofluorescence for polarity markers (scribble, discs large [Dlg] and partitioning defective 3 homologue [Par3]) and presynaptic markers (liprin, Rab3-interacting protein [RIM2] and piccolo) and imaged using 3D confocal microscopy. Isolated human islets were dispersed and cultured on laminin-511-coated coverslips. Live 3D two-photon microscopy was used on cultured cells to image exocytic granule fusion events upon glucose stimulation. Results Assessment of the distribution of endocrine cells across human islets found that, despite distinct islet-to-islet complexity and variability, including multi-lobular islets, and intermixing of alpha and beta cells, there is still a striking enrichment of alpha cells at the islet mantle. Measures of cell position demonstrate that most beta cells contact islet capillaries. Subcellularly, beta cells consistently position polar determinants, such as Par3, Dlg and scribble, with a basal domain towards the capillaries and apical domain at the opposite face. The capillary interface/vascular face is enriched in presynaptic scaffold proteins, such as liprin, RIM2 and piccolo. Interestingly, enrichment of presynaptic scaffold proteins also occurs where the beta cells contact peri-islet capillaries, suggesting functional interactions. We also observed the same polarisation of synaptic scaffold proteins in islets from type 2 diabetic patients. Consistent with polarised function, isolated beta cells cultured onto laminin-coated coverslips target insulin granule fusion to the coverslip. Conclusions/interpretation Structural and functional polarisation is a defining feature of human pancreatic beta cells and plays an important role in the control of insulin secretion. Graphical abstract

Osteoprotegerin (OPG) protects pancreatic beta cells from Interleukin-1 induced cell death

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
J Schrader ◽  
U Niebergall ◽  
M Schoppet ◽  
D Hörsch ◽  
LC Hofbauer
Keyword(s):  
Cell Death ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Interleukin 1
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