scholarly journals The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes

2015 ◽  
Vol 21 (6) ◽  
pp. 619-627 ◽  
Author(s):  
Bengt-Frederik Belgardt ◽  
Kashan Ahmed ◽  
Martina Spranger ◽  
Mathieu Latreille ◽  
Remy Denzler ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Survival ◽  
Pancreatic Beta Cell

scholarly journals The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Marta Letizia Hribal ◽  
Elettra Mancuso ◽  
Gaetano Paride Arcidiacono ◽  
Annalisa Greco ◽  
Donatella Musca ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Survival ◽  
High Glucose ◽  
Chronic Exposure ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Pleckstrin Homology Domain ◽  
Causative Role

Currently available antidiabetic treatments fail to halt, and may even exacerbate, pancreatic β-cell exhaustion, a key feature of type 2 diabetes pathogenesis; thus, strategies to prevent, or reverse, β-cell failure should be actively sought. The serine threonine kinase Akt has a key role in the regulation of β-cell homeostasis; among Akt modulators, a central role is played by pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) family. Here, taking advantage of an in vitro model of chronic exposure to high glucose, we demonstrated that PHLPPs, particularly the second family member called PHLPP2, are implicated in the ability of pancreatic β cells to deal with glucose toxicity. We observed that INS-1 rat pancreatic β cell line maintained for 12–15 passages at high (30 mM) glucose concentrations (INS-1 HG) showed increased expression of PHLPP2 and PHLPP1 both at mRNA and protein level as compared to INS-1 maintained for the same number of passages in the presence of normal glucose levels (INS-1 NG). These changes were paralleled by decreased phosphorylation of Akt and by increased expression of apoptotic and autophagic markers. To investigate if PHLPPs had a casual role in the alteration of INS-1 homeostasis observed upon chronic exposure to high glucose concentrations, we took advantage of shRNA technology to specifically knock-down PHLPPs. We obtained proof-of-concept evidence that modulating PHLPPs expression may help to restore a healthy β cell mass, as the reduced expression of PHLPP2/1 was accompanied by a recovered balance between pro- and antiapoptotic factor levels. In conclusion, our data provide initial support for future studies aimed to identify pharmacological PHLPPs modulator to treat beta-cell survival impairment. They also contribute to shed some light on β-cell dysfunction, a complex and unsatisfactorily characterized phenomenon that has a central causative role in the pathogenesis of type 2 diabetes.

scholarly journals A Common Functional Regulatory Variant at a Type 2 Diabetes Locus Upregulates ARAP1 Expression in the Pancreatic Beta Cell

2014 ◽  
Vol 94 (2) ◽  
pp. 186-197 ◽  
Author(s):  
Jennifer R. Kulzer ◽  
Michael L. Stitzel ◽  
Mario A. Morken ◽  
Jeroen R. Huyghe ◽  
Christian Fuchsberger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Regulatory Variant

scholarly journals A role for pancreatic beta-cell secretory hyperresponsiveness in catch-up growth hyperinsulinemia: Relevance to thrifty catch-up fat phenotype and risks for type 2 diabetes

2011 ◽  
Vol 8 (1) ◽  
pp. 2 ◽  
Author(s):  
Marina Casimir ◽  
Paula B de Andrade ◽  
Asllan Gjinovci ◽  
Jean-Pierre Montani ◽  
Pierre Maechler ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Catch Up

scholarly journals THE ROLE OF SURVIVIN AND RAF-1 KINASE AGAINST ENHANCEMENT OF PANCREATIC BETA-CELL APOPTOSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

2018 ◽  
Vol 11 (11) ◽  
pp. 344
Author(s):  
Eva Decroli ◽  
Asman Manaf ◽  
Syafril Syahbuddin ◽  
Sarwono Waspadji ◽  
Dwisari Dillasamola
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Beta Cell Apoptosis

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.

scholarly journals Autophagy and the pancreatic beta-cell in human type 2 diabetes

Autophagy ◽  
2009 ◽  
Vol 5 (7) ◽  
pp. 1055-1056 ◽  
Author(s):  
Piero Marchetti ◽  
Matilde Masini
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
Human Type
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