Adiponectin-induced ERK and Akt Phosphorylation Protects against Pancreatic Beta Cell Apoptosis and Increases Insulin Gene Expression and Secretion

Objective: This study aimed to reveal differences in levels of survivin and Raf-1 kinase in prediabetes, controlled Type 2 diabetes mellitus (T2DM), uncontrolled T2DM, and their relationship with hemoglobin A1c (HbA1c) levels and serum triglyceride levels.Methods: This study was an observational study with a cross-sectional design. The study involved 60 people with T2DM who visited the endocrine and metabolic clinic and 30 prediabetes patients. The variables were survivin levels and Raf-1 kinase enzymes that examined using enzyme-linked immunosorbent assay techniques. HbA1c values are measured by high-performance liquid chromatography and triglyceride levels measured by enzymatic method.Results: Average levels of Raf-1 kinase were significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (11.6±1.4 pg mL, 9.9±1.1 pg/mL, and 9.1±1.5 pg/mL). Survivin was significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (5.4±0.4 pg mL, 5.0±0.2 pg/mL, and 4.7±0.1 pg/mL). There was no correlation between HbA1c with Raf-1 kinase levels (R=−0.215, p=0.250), but there was a correlation between HbA1c with serum survivin levels (R=−0.6, *p<0.05). There was a correlation between the levels of triglycerides with survivin but not with Raf-1 kinase (R=−0.267, *p=0.039).Conclusion: Survivin and Raf-1 kinase levels are lower in uncontrolled T2DM. This explained the role of survivin and Raf-1 kinase against enhancement of pancreatic beta-cell apoptosis in patients with T2DM.

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miR-149-5p protects against high glucose-induced pancreatic beta cell apoptosis via targeting the BH3-only protein BIM

Experimental and Molecular Pathology ◽

10.1016/j.yexmp.2019.104279 ◽

2019 ◽

Vol 110 ◽

pp. 104279 ◽

Cited By ~ 5

Author(s):

Dongyun Ruan ◽

Yanfeng Liu ◽

Xiaoqing Wang ◽

Dahao Yang ◽

Yan Sun

Keyword(s):

Beta Cell ◽

High Glucose ◽

Cell Apoptosis ◽

Pancreatic Beta Cell ◽

Beta Cell Apoptosis

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530 BRCA1 is a Novel Molecular Target to Limit Pancreatic Beta Cell Apoptosis and Restore Beta Cell Function

Canadian Journal of Cardiology ◽

10.1016/j.cjca.2012.07.483 ◽

2012 ◽

Vol 28 (5) ◽

pp. S296

Author(s):

K.K. Singh ◽

F. Lovren ◽

A. Quan ◽

Y. Pan ◽

H. Teoh ◽

...

Keyword(s):

Beta Cell ◽

Cell Apoptosis ◽

Beta Cell Function ◽

Cell Function ◽

Pancreatic Beta Cell ◽

Molecular Target ◽

Beta Cell Apoptosis

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GLIS3, a Susceptibility Gene for Type 1 and Type 2 Diabetes, Modulates Pancreatic Beta Cell Apoptosis via Regulation of a Splice Variant of the BH3-Only Protein Bim

PLoS Genetics ◽

10.1371/journal.pgen.1003532 ◽

2013 ◽

Vol 9 (5) ◽

pp. e1003532 ◽

Cited By ~ 98

Author(s):

Tatiane C. Nogueira ◽

Flavia M. Paula ◽

Olatz Villate ◽

Maikel L. Colli ◽

Rodrigo F. Moura ◽

...

Keyword(s):

Type 2 Diabetes ◽

Beta Cell ◽

Cell Apoptosis ◽

Splice Variant ◽

Pancreatic Beta Cell ◽

Susceptibility Gene ◽

Beta Cell Apoptosis

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Mitochondrial and insulin gene expression in single cells shape pancreatic beta cells’ population divergence

10.1101/2020.07.21.213801 ◽

2020 ◽

Author(s):

H. Medini ◽

T. Cohen ◽

D. Mishmar

Keyword(s):

Gene Expression ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Single Cells ◽

Insulin Gene ◽

Population Divergence ◽

Cell Populations ◽

Alpha Cells ◽

Insulin Gene Expression

AbstractMitochondrial gene expression is pivotal to cell metabolism. Nevertheless, it is unknown whether it diverges within a given cell type. Here, we analysed single-cell RNA-seq experiments from ∼4600 human pancreatic alpha and beta cells, as well as ∼900 mouse beta cells. Cluster analysis revealed two distinct human beta cells populations, which diverged by mitochondrial (mtDNA) and nuclear DNA (nDNA)-encoded oxidative phosphorylation (OXPHOS) gene expression in healthy and diabetic individuals, and in newborn but not in adult mice. Insulin gene expression was elevated in beta cells with higher mtDNA gene expression in humans and in young mice. Such human beta cell populations also diverged in mt-RNA mutational repertoire, and in their selective signature, thus implying the existence of two previously overlooked distinct and conserved beta cell populations. While applying our approach to alpha cells, two sub-populations of cells were identified which diverged in mtDNA gene expression, yet these cellular populations did not consistently diverge in nDNA OXPHOS genes expression, nor did they correlate with the expression of glucagon, the hallmark of alpha cells. Thus, pancreatic beta cells within an individual are divided into distinct groups with unique metabolic-mitochondrial signature.

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The adaptor protein NumbL is involved in the control of glucolipotoxicity-induced pancreatic beta cell apoptosis

10.1101/2020.08.16.253286 ◽

2020 ◽

Author(s):

Halesha D. Basavarajappa ◽

Jose M. Irimia ◽

Patrick T. Fueger

Keyword(s):

Cell Death ◽

Beta Cell ◽

Beta Cells ◽

Cell Apoptosis ◽

Molecular Mechanisms ◽

Pancreatic Beta Cell ◽

Adaptor Protein ◽

Beta Cell Apoptosis ◽

Beta Cell Death ◽

Egf Signaling

AbstractAvoiding loss of functional beta cell mass is critical for preventing or treating diabetes. Currently, the molecular mechanisms underlying beta cell death are partially understood, and there is a need to identify new targets for developing novel therapeutics to treat diabetes. Previously, our group established that Mig6, an inhibitor of EGF signaling, mediates beta cell death under diabetogenic conditions. The objective of this study was to clarify the mechanisms linking diabetogenic stimuli to beta cell death by investigating Mig6-interacting proteins. Using co-immunoprecipitation and mass spectrometry, we evaluated the binding partners of Mig6 under both normal glucose (NG) and glucolipotoxic (GLT) conditions in beta cells. We identified that Mig6 interacts dynamically with NumbL; whereas Mig6 associates with NumbL under NG, this interaction is disrupted under GLT conditions. Further, we demonstrate that siRNA-mediated suppression of NumbL expression in beta cells prevented apoptosis under GLT conditions by blocking activation of NF-κB signaling. Using co-immunoprecipitation experiments we observed that NumbL’s interactions with TRAF6, a key component of NFκB signaling, are increased under GLT conditions. The interactions among Mig6, NumbL, and TRAF6 are dynamic and context-dependent. We propose a model wherein these interactions activate pro-apoptotic NF-κB signaling while blocking pro-survival EGF signaling under diabetogenic conditions, leading to beta cell apoptosis. These findings indicate that NumbL should be further investigated as a candidate anti-diabetic therapeutic target.

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