M19 Modulates Skeletal Muscle Differentiation and Insulin Secretion in Pancreatic β-Cells through Modulation of Respiratory Chain Activity

Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion

Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets

Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory process. That the latter could contribute to β-cell hyperactivity/proliferation and possibly lead to progressive β-cell failure in these animals, deserves further investigations

Paul Pouchol, le potier de Saint-Germain-des-Prés. Paris, 21 juillet 1904-1963

Lajoix Anne. Paul Pouchol, le potier de Saint-Germain-des-Prés. Paris, 21 juillet 1904-1963 . In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°13, 2004. p. 103

Alexandre Brongniart et la quête des moyens de reproduction en couleurs

Lajoix Anne. Alexandre Brongniart et la quête des moyens de reproduction en couleurs. In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°1, 1992. pp. 64-73

Colette Guéden (1905–2000). Primavera et la céramique

Lajoix Anne. Colette Guéden (1905–2000). Primavera et la céramique. In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°18, 2009. pp. 99-106

De la céramique chez un orfèvre, Christofle, 1942-1972

Lajoix Anne. De la céramique chez un orfèvre, Christofle, 1942-1972. In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°5, 1996. pp. 7-18

Auguste Rodin et les arts du feu

Lajoix Anne. Auguste Rodin et les arts du feu. In: Revue de l'Art, 1997, n°116. pp. 76-88

Antoine-Émile Bourdelle et les arts du feu. Les aléas de la polychromie

Lajoix Anne. Antoine-Émile Bourdelle et les arts du feu. Les aléas de la polychromie. In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°9, 2000. pp. 60-81

Alexandre Brongniart et la quête des moyens de reproduction en couleurs (II). (suite)

Lajoix Anne. Alexandre Brongniart et la quête des moyens de reproduction en couleurs (II). (suite). In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°2, 1993. pp. 76-78

L'Eau et le Feu

Lajoix Anne. L'Eau et le Feu. In: Sèvres. Revue de la Société des Amis du musée national de Céramique, n°25, 2016. pp. 162-173