INCREMENT OF COMPLEXIN-2 IN INSULIN RESISTANCE-LIKE STATES. POSSIBLE INVOLVEMENT IN DEFICIENT GLUT4-TRANSLOCATION

ZANNI RUIZ EMILIA.; LARITO SERGIO; MAYORGA LUIS S.; PAVAROTTI MARTÍN A

Mendoza

Congreso; LVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research (SAIB); 2023

SAIB

Introduction: Insulin-induced glucose uptake in muscle and adipose tissue is mediated by the glucose transporter GLUT4. In theresting state, GLUT4 is stored in intracellular compartments (recycling compartment and vesicles GSVs -GLUT4 store vesiclesandIRVs -insulin-responsive vesicles-). The insulin increase promotes the trafficking and fusion of GSV/IRV with the plasmamembrane (MP), therefore increasing the levels of GLUT4 on the cell surface (GLUT4 exocytosis). As with many exocyticprocesses, in GLUT4 exocytosis the SNAREs and accessory proteins play a major role in regulating GSV/IRV fusion with MP.Our group has recently shown, for the first time, the existence of complexin2 both in muscle tissue and in myoblastic cells, which,upon insulin stimulus, migrates towards MP. We also show that the lack and excess of complexin2 decrease GLUT4 exocytosis,these observations being consistent with the role of complexin2 in the stabilization of the trans-SNARE complex. On the otherhand, there is evidence that the sustained insulin stimulus, (given by a high yeast diet), induces an increase in complexin levels,compromising motor neurotransmission in Drosophila. Objective: To evaluate the expression level of complexin2 in myoblasticcells maintained under conditions of high insulin concentration for prolonged periods (insulin resistance conditions). Materials andMethods: L6 myoblast cells were incubated with 100nM insulin for 2, 4, and 7 days. The level of protein expression and mRNAwere evaluated by Western blot and RT-PCR, respectively. Results: So far, the results show a gradual increase in both the proteinand the mRNA of complexin2. Conclusions: The increase in mRNA and protein would indicate an increase in the transcription andtranslation of complexin2 by insulin action. Based on the mechanism of action of complexin on the SNARE complex in otherworking models, and based on our results in L6 cells, we believe that the increase in complexin2 observed by high concentrationsof insulin could slow down or decrease GLUT4 exocytosis, contributing, at least partially with to the decrease of GLUT4 over thecell surface observed in states of insulin resistance.