Figure 5.

Loss of K_ATP channel conductance underlies a left shift in the glucose threshold of aged mouse β-cells. A: Recording of islet Ca²⁺ in response to increased glucose levels. B: Glucose dependence of plateau fraction calculated from simultaneous recordings of Ca²⁺ (Fura Red) and ATP/ADP (PercevalHR) oscillations using MATLAB. C: Ca²⁺ and ATP/ADP oscillations in young (6-month-old) and aged (24-month-old) C57BL/6J mouse islet β-cells in the presence of 10 mmol/L glucose (10G). D: The oscillatory plateau fraction, reflecting the plasma membrane glucose sensitivity, was calculated as the fraction of time spent in the active state of each oscillation. Young, 124 islets from four mice; aged, 210 islets from five mice. E and F: Representative current-voltage relation (I-V) curves showing slope conductance changes in islet β-cells during the silent phase (SP) of bursting (10G) and 5 min after treatment with 200 μmol/L diazoxide (DZ). Average K_ATP conductance as well as conductance difference (DZ – SP) were reduced in aged β-cells (eight cells from three mice) relative to young controls (19 cells from four mice). Data are mean ± SEM and were compared by two-way ANOVA with Sidak posttest. *P < 0.05; **P < 0.01; ****P < 0.0001.