THE POTASSIUM CHANNEL KIR6.2/K-ATP PARTICIPATES IN LIPID AND CARBOHYDRATE METABOLISMS IN THE MOUSE

HEIT-BARBINI FJ; BAEZ ROSES, I; CANALE VAGLIENTE, F; COMANZO, CG; VERA, MC; LUCCI, A; LORENZETTI, F; CARRILLO, MC; CEBALLOS, MP; ALVAREZ, ML; QUIROGA, AD

Congreso; Sociedad Argentina de Investigaciones Clinicas; 2018

Obesity is characterized by excessive accumulation of fat. It is relatedto the metabolic syndrome and its associated pathologies such asdiabetes, hypertension, atherosclerosis, dyslipidemia and hyperuricemia.ATP-sensitive potassium channels (K-ATP) are composed of4 protein subunits Kir6.x (6.1 or 6.2) that form the pore, and 2 regulatorysubunits. Kir6.2/K-ATPs couple metabolism with cell membranepotential, and regulate several cellular activities acting as metabolicsensors, especially in response to situations of cellular metabolicstress such as hyper or hypoglycemia, ischemia and hypoxia. Basedon this, we asked: does Kir6.2/ATP play a role in lipid metabolism?If so, is it direct or indirect? We worked with male C57/B6, wild-type(WT) and Kir6.2-/- mice (n=7) subjected to a high fat diet (HFD)for 2 months. We measured several metabolic parameters beforeand after the HFD. Before HFD: Body weight (BW) was similarfor both groups (WT: 19.14±0.30g; Kir6.2-/-: 17.90±0.08g). Serummarkers of liver function (alanine and aspartate aminotransferasesand alkaline phosphatase) did not differ between genotypes. Basalblood glucose levels were considerable different: WT: 103,6±5.7g/L;Kir6.2-/-: 36.0±4.5g/L#). WT mice responded as expected to the oralglucose tolerance test (OGTT); however, Kir6.2-/- showed a markedbasal incapacity to lower plasma glucose levels. Plasma triacylglyceroland cholesterol levels were similar for both groups. UponHFD: Liver damage markers were slightly increased (still no significant)in Kir6.2-/- mice. BW was, as expected, increased in WT mice(31.90±0.74g); however Kir6.2-/- seemed resistant to HFD-inducebody weight increase (23.90±0.28g*). OGTT for WT mice showednow a clear incapacity to lower plasma glucose levels; no significantchanges were observed in Kir6.2-/- mice respect to the initial time.Plasma triacylglycerol and cholesterol levels for both groups wereincreased respect to initial time, but not different (*p