Autophagy in human type 2 diabetes pancreatic beta cells
| Autor: | Matilde Masini, Ugo Boggi, M. Bugliani, Lorella Marselli, S Del Guerra, R. Lupi, Piero Marchetti, Franco Filipponi, Pellegrino Masiello |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death Endocrinology Diabetes and Metabolism Type 2 diabetes Protein Serine-Threonine Kinases Biology Cathepsin D Cathepsin B Microscopy Electron Transmission Insulin-Secreting Cells Lysosomal-Associated Membrane Protein 2 Internal medicine Diabetes mellitus Organelle Autophagy Internal Medicine medicine Autophagy-Related Protein-1 Homolog Humans Aged Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins Lysosome-Associated Membrane Glycoproteins Membrane Proteins Middle Aged medicine.disease Metformin Endocrinology Diabetes Mellitus Type 2 Apoptosis Cancer research Beclin-1 Female Beta cell Apoptosis Regulatory Proteins medicine.drug |
| Zdroj: | Diabetologia. 52:1083-1086 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-009-1347-2 |
| Popis: | Beta cell loss contributes to type 2 diabetes, with increased apoptosis representing an underlying mechanism. Autophagy, i.e. the physiological degradation of damaged organelles and proteins, may, if altered, be associated with a distinct form of cell death. We studied several features of autophagy in beta cells from type 2 diabetic patients and assessed the role of metabolic perturbation and pharmacological intervention.Pancreatic samples were obtained from organ donors and isolated islets prepared both by collagenase digestion and density gradient centrifugation. Beta cell morphology and morphometry were studied by electron microscopy. Gene expression studies were performed by quantitative RT-PCR.Using electron microscopy, we observed more dead beta cells in diabetic (2.24 +/- 0.53%) than control (0.66 +/- 0.52%) samples (p0.01). Massive vacuole overload (suggesting altered autophagy) was associated with 1.18 +/- 0.54% dead beta cells in type 2 diabetic samples and with 0.36 +/- 0.26% in control samples (p0.05). Density volume of autophagic vacuoles and autophagosomes was significantly higher in diabetic beta cells. Unchanged gene expression of beclin-1 and ATG1 (also known as ULK1), and reduced transcription of LAMP2 and cathepsin B and D was observed in type 2 diabetic islets. Exposure of non-diabetic islets to increased NEFA concentration led to a marked increase of vacuole accumulation, together with enhanced beta cell death, which was associated with decreased LAMP2 expression. Metformin ameliorated autophagy alterations in diabetic beta cells and beta cells exposed to NEFA, a process associated with normalisation of LAMP2 expression.Beta cells in human type 2 diabetes have signs of altered autophagy, which may contribute to loss of beta cell mass. To preserve beta cell mass in diabetic patients, it may be necessary to target multiple cell-death pathways. |
| Databáze: | OpenAIRE |
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