OBJECTIVE— We studied how glucose and ATP-sensitive K + (K ATP ) channel modulators affect α-cell [Ca 2+ ] c . RESEARCH DESIGN AND METHODS— GYY mice (expressing enhanced yellow fluorescent protein in α-cells) and NMRI mice were used. [Ca 2+ ] c , the K ATP current (I KATP , perforated mode) and cell metabolism [NAD(P)H fluorescence] were monitored in single α-cells and, for comparison, in single β-cells. RESULTS— In 0.5 mmol/l glucose, [Ca 2+ ] c oscillated in some α-cells and was basal in the others. Increasing glucose to 15 mmol/l decreased [Ca 2+ ] c by ∼30% in oscillating cells and was ineffective in the others. α-Cell I KATP was inhibited by tolbutamide and activated by diazoxide or the mitochondrial poison azide, as in β-cells. Tolbutamide increased α-cell [Ca 2+ ] c , whereas diazoxide and azide abolished [Ca 2+ ] c oscillations. Increasing glucose from 0.5 to 15 mmol/l did not change I KATP and NAD(P)H fluorescence in α-cells in contrast to β-cells. The use of nimodipine showed that L-type Ca 2+ channels are the main conduits for Ca 2+ influx in α-cells. γ-Aminobutyric acid and zinc did not decrease α-cell [Ca 2+ ] c , and insulin, although lowering [Ca 2+ ] c very modestly, did not affect glucagon secretion. CONCLUSIONS— α-Cells display similarities with β-cells: K ATP channels control Ca 2+ influx mainly through L-type Ca 2+ channels. However, α-cells have distinct features from β-cells: Most K ATP channels are already closed at low glucose, glucose does not affect cell metabolism and I KATP , and it slightly decreases [Ca 2+ ] c . Hence, glucose and K ATP channel modulators exert distinct effects on α-cell [Ca 2+ ] c . The direct small glucose-induced drop in α-cell [Ca 2+ ] c contributes likely only partly to the strong glucose-induced inhibition of glucagon secretion in islets.

Low-density lipoprotein (LDL) oxidation is a key step in atherogenesis, promoting the formation of lipid-laden macrophages. Here, we compared the effects of copper-oxidized LDLs (OxLDLs) and of the more physiologically relevant myeloperoxidase-oxidized LDLs (MoxLDLs) in murine RAW264.7 macrophages and in human peripheral blood monocyte-derived macrophages. Both oxidized LDLs, contrary to native LDLs, induced foam cell formation and an intracellular accumulation of reactive oxygen species (ROS). This oxidative stress was responsible for the activation of the NF-E2-related factor 2 (Nrf2) transcription factor, and the subsequent Nrf2-dependent overexpression of the antioxidant genes, Gclm and HO-1, as evidenced by the invalidation of Nrf2 by RNAi. MoxLDLs always induced a stronger response than OxLDLs. These differences could be partly explained by specific ROS-producing mechanisms differing between OxLDLs and MoxLDLs. Whereas both types of oxidized LDLs caused ROS production partly by NADPH oxidase, only MoxLDLs-induced ROS production was dependent on cytosolic PLA2. This study highlights that OxLDLs and MoxLDLs induce an oxidative stress, through distinct ROS-producing mechanisms, which is responsible for the differential activation of the Nrf2 pathway. These data clearly suggest that results obtained until now with copper oxidized-LDLs should be carefully reevaluated, taking into consideration physiologically more relevant oxidized LDLs.

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At the end of 2008, a new left colon clinical pathway was implemented in our hospital and set up by a multidisciplinary team, monitored by a clinical pathway coordinator. Our aim was to evaluate the quality of left and sigmoid colectomy management, to simplify the clinical pathway and to assess its impact on the patient, the medical and nursing staffs.A sample of 290 patients with benign or malignant disease requiring a laparoscopic of laparotomy left colon resection (mainly sigmoid) was included in this clinical pathway during the years 2009-2017. Our analysis focused particularly on the compliance with the protocol, the pain felt, the suture leak rate, the hospital stay, the re-hospitalization rate and redo surgery within 30 days. Our work leads to the conclusion that the introduction of a clinical pathway, when it is well prepared and brings together all the implicated persons with the same goal, is feasible with convincing results. These are directly beneficial to the patient and to the quality of its management.