PTEN expression and its association with glucose control and calorie supplementation in critically ill patients.

BACKGROUND & AIM: Phosphatase and tensin homologue (PTEN) reduces insulin sensitivity. Since critically ill patients present insulin resistance, we aimed at assessing the role of PTEN expression on glucose homeostasis and clinical outcome in patients admitted to an intensive care unit (ICU) and receiving artificial nutrition. METHODS: Observational, single-center study conducted in one ICU in Rome, Italy on adult patients hospitalized for trauma. Plasma glucose levels and its variability were recorded in patients receiving artificial nutrition. PTEN expression was measured by western blotting analysis and the associations between PTEN, plasma glucose levels and variability, and calories administered were investigated. Parametric and non-parametric tests were used, as appropriate. RESULTS: Twenty consecutive patients (13 men and 7 women, mean age of 37.3 ± 12.7 years) were studied. No correlation between plasma glucose and PTEN was documented (r = -0.15, P = 0.55), neither between glycemic variability and PTEN expression (r = -0.00, P = 0.99). However, total kcal/day administered and PTEN expression significantly correlated (r = 0.56, P = 0.01). Also, patients with PTEN levels below the median received less kcal/day than those with PTEN above the median (P = 0.048). This association was more pronounced when normalized per body weight (P = 0.03) and after adjusting for the average of insulin daily administered (P = 0.02). CONCLUSIONS: PTEN expression might significantly contribute to glucose homeostasis and disposal in critically ill patients receiving artificial nutrition. Larger samples are necessary to confirm our observation. CLINICAL TRIAL REGISTRY NUMBER: NCT01796847 (www.clinicaltrials.gov) submitted on February 11, 2013.

Metabotropic glutamate receptors in stem/progenitor cells.

Functional mGlu receptor subtypes are found in stem/progenitor cells, and regulate proliferation, differentiation, and survival of these cells. Activation of mGlu5 receptors supports self-renewal of embryonic stem cells, which are pluripotent cells isolated from the blastocyst capable of generating all the body's cell lineages, including germ cells. Differentiation of embryonic stem cells into embryoid bodies is associated with the induction of mGlu4 receptors, the activation of which drives cell differentiation towards the mesoderm and endoderm lineages. Different mGlu receptor subtypes, mGlu3 and mGlu5 receptors in particular, are found in neural stem cells (stem cells resident in the CNS that give rise to neurons, astrocytes or oligodendrocytes) isolated from the developing brain or from regions of persistent neurogenesis of the adult brain (e.g. the subventricular zone lining the wall of the lateral ventricles). The evidence that activation of mGlu3 and mGlu5 receptors stimulates proliferation of these cells is particularly interesting because of the similarities between neural stem cells and putative cancer stem cells that support the growth of malignant gliomas. A link among mGlu receptors, stem cells and cancer is supported by the finding that mGlu4 receptors are expressed by cerebellar granule cell neuroprogenitors, which are the putative cells of origin of medulloblastomas. The study of mGlu receptors in stem/progenitor cells has potential applications in the optimisation of protocols of cell expansion and differentiation aimed at cell replacement strategies, and may gain new insights into the pathophysiology of neurodevelopmental disorders and brain tumours.