Translationally controlled tumour protein (TCTP) is a novel glucose-regulated protein that is important for survival of pancreatic beta cells

• Published in: Diabetologia Vol. 54; no. 2; pp. 368 - 379
• Main Authors: Diraison, F, Hayward, K, Sanders, K. L, Brozzi, F, Lajus, S, Hancock, J, Francis, J. E, Ainscow, E, Bommer, U. A, Molnar, E, Avent, N. D, Varadi, A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-02-2011; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell growth; Cell Line; Cell Survival - drug effects; Cell Survival - genetics; Diabetes. Impaired glucose tolerance; Electrophoresis, Gel, Two-Dimensional; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acid palmitate; Glucose; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Human Physiology; Humans; In Situ Nick-End Labeling; Insects; insulin secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Internal Medicine; Investigations; Isoelectric Focusing; Kinases; Leukemia; Life sciences; Lymphoma; Medical sciences; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolic Diseases; Mice; Palmitic Acids - pharmacology; Proteins; Proteomics; Proteomics analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; TCTP; Translationally controlled tumour protein; Tumor Protein, Translationally-Controlled 1; United Kingdom > UK; Translationally controlled tumour protein; Proteomics analysis; TCTP; Fatty acid palmitate; Apoptosis; Insulin secretion; Endocrinopathy; Pancreatic hormone; Secretion; Diabetes mellitus; Langerhans islet; Lipids; Glucose; Fatty acids; Insulin; Survival; Protein; Cell death; Tumor; Fatty acid pahnitate; β Cell; Endocrine pancreas
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-010-1958-7

Aims/hypothesis This study used proteomics and biochemical approaches to identify novel glucose-regulated proteins and to unveil their role in pancreatic beta cell function. Translationally controlled tumour protein (TCTP) was identified to be one such protein, and further investigations into its function and regulation were carried out. Methods Global protein profiling of beta cell homogenates following glucose stimulation was performed using two-dimensional gel electrophoresis. Proteins were identified by mass spectroscopy analysis. Immunoblotting was used to investigate alterations in TCTP protein levels in response to glucose stimulation or cell stress induced by palmitate. To investigate the biological function of TCTP, immunolocalisation, gene knockdown and overexpression of Tctp (also known as Tpt1) were performed. Apoptosis was measured in Tctp knockdown or Tctp-overexpressing cells. Glucose-stimulated insulin secretion was carried out in Tctp knockdown cells. Results TCTP was identified as a novel glucose-regulated protein, the level of which is increased at stimulatory glucose concentration. Glucose also induced TCTP dephosphorylation and its partial translocation to the mitochondria and the nucleus. TCTP protein levels were downregulated in response to cell stress induced by palmitate or thapsigargin treatments. Gene knockdown by small interfering RNA led to increased apoptosis, whereas overproduction of TCTP prevented palmitate-induced cell death. Conclusions/interpretation Regulation of TCTP protein levels by glucose is likely to be an important cyto-protective mechanism for pancreatic beta cells against damage caused by hyperglycaemia. In contrast, high concentration of palmitate causes cell stress, reduction in TCTP levels and consequently reduced cell viability. Our results imply that TCTP levels influence the sensitivity of beta cells to apoptosis.