Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin

Objective Chondrocytes respond to insulin, but the presence and role of the specific high affinity insulin receptor (InsR) has never been demonstrated. This study determined whether human chondrocytes express the InsR and compared its abundance and function in normal and osteoarthritis (OA) human chondrocytes. Design Cartilage sections were immunostained for detection of the InsR. Non-proliferating chondrocyte cultures from normal and OA human cartilage were treated with 1 nM or 10 nM insulin for various periods. InsR, insulin-like growth factor receptor (IGFR), aggrecan and collagen II mRNA levels were assessed by real time RT-PCR. InsR, glucose transporter (GLUT)-1, phospho-InsRbeta and phospho-Akt were evaluated by western blot and immunofluorescence. Glucose transport was measured as the uptake of [3H]-2-Deoxy-d-Glucose (2-DG). Results Chondrocytes staining positively for the InsR were scattered throughout the articular cartilage. The mRNA and protein levels of the InsR in OA chondrocytes were approximately 33% and 45%, respectively, of those found in normal chondrocytes. Insulin induced the phosphorylation of the InsRbeta subunit. Akt phosphorylation and 2-DG uptake increased more intensely in normal than OA chondrocytes. Collagen II mRNA expression increased similarly in normal and OA chondrocytes while aggrecan expression remained unchanged. The Phosphoinositol-3 Kinase (PI3K)/Akt pathway was required for both basal and insulin-induced collagen II expression. Conclusions Human chondrocytes express functional InsR that respond to physiologic insulin concentrations. The InsR seems to be more abundant in normal than in OA chondrocytes, but these still respond to physiologic insulin concentrations, although some responses are impaired while others appear fully activated. Understanding the mechanisms that regulate the expression and function of the InsR in normal and OA chondrocytes can disclose new targets for the development of innovative therapies for OA

Amplitude, frequency and drivers of Caspian Sea lake-level variations during the Early Pleistocene and their impact on a protected wave-dominated coastline

The Caspian Sea, the largest isolated lake in the world, witnessed drastic lake-level variations during the Quaternary. This restricted basin appears very sensitive to lake-level variations, due to important variations in regional evaporation, precipitation and runoff. The amplitude, frequency and drivers of these lake-level changes are still poorly documented and understood. Studying geological records of the Caspian Sea might be the key to better comprehend the complexity of these oscillations. The Hajigabul section documents sediment deposited on the northern margin of the Kura Basin, a former embayment of the Caspian Sea. The 2035 m thick, well-exposed section was previously dated by magneto-biostratigraphic techniques and provides an excellent record of Early Pleistocene environmental, lake-level and climate changes. Within this succession, the 1050 m thick Apsheronian regional stage, between ca 2·1 Ma and 0·85 Ma, represents a particular time interval with 20 regressive sequences documented by sedimentary and palaeontological changes. Sequences are regressing from offshore to coastal, lagoonal or terrestrial settings and are bounded by abrupt flooding events. Sediment reveals a low energy, wave-dominated, reflective beach system. Wave baselines delimiting each facies association appear to be located at shallower bathymetries compared to the open ocean. Water depth estimations of the wave baselines allow reconstruction of a lake-level curve, recording oscillations of ca 40 m amplitude. Cyclostratigraphic analyses display lake-level frequency close to 41 kyr, pointing to allogenic forcing, dominated by obliquity cycles and suggesting a direct or indirect link with high-latitude climates and environments. This study provides a detailed lake-level curve for the Early Pleistocene Caspian Sea and constitutes a first step towards a better comprehension of the magnitude, occurrence and forcing mechanisms of Caspian Sea lake-level changes. Facies models developed in this study regarding sedimentary architectures of palaeocoastlines affected by repeated lake-level fluctuations may form good analogues for other (semi-)isolated basins worldwide

Nutrition. Y a-t-il une place pour la supplémentation en acides gras oméga-3, en acides linoléiques conjugués et en micronutriments pendant et après les traitements d’un cancer du sein ?

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