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Property "Has-20abstract" (as page type) with input value "Aging-20is-20accompanied-20by-20impaired-20glucose-20homeostasis-20and-20an-20increased-20risk-20of-20type-202-20diabetes,-20culminating-20in-20the-20failure-20of-20insulin-20secretion-20from-20pancreatic-20β-20cells.-20To-20investigate-20the-20effects-20of-20age-20on-20β-20cell-20metabolism,-20we-20established-20a-20novel-20assay-20to-20directly-20image-20islet-20metabolism-20using-20NAD(P)H-20fluorescence-20lifetime-20imaging-20(FLIM).-20We-20determined-20that-20impaired-20mitochondrial-20activity-20underlies-20an-20age-2Ddependent-20loss-20of-20insulin-20secretion-20in-20human-20islets.-20NAD(P)H-20FLIM-20revealed-20a-20comparable-20decline-20in-20mitochondrial-20function-20in-20the-20pancreatic-20islets-20of-20aged-20mice-20(≥-2024-20months),-20resulting-20from-2052-25-20and-2057-25-20defects-20in-20flux-20through-20complex-20I-20and-20II-20of-20the-20electron-20transport-20chain.-20However,-20insulin-20secretion-20and-20glucose-20tolerance-20are-20preserved-20in-20aged-20mouse-20islets-20by-20the-20heightened-20metabolic-20sensitivity-20of-20the-20β-20cell-20triggering-20pathway,-20an-20adaptation-20clearly-20encoded-20in-20the-20metabolic-20and-20Ca-3Csub-3E2+-3C-2Fsub-3E-20oscillations-20that-20trigger-20insulin-20release-20(Ca-3Csub-3E2+-3C-2Fsub-3E-20plateau-20fraction:-20young,-200.211-20±-200.006-3B-20aged,-200.380-20±-200.007,-20P-20-3C-200.0001).-20This-20enhanced-20sensitivity-20is-20driven-20by-20a-20reduction-20in-20K-3Csub-3EATP-3C-2Fsub-3E-20channel-20conductance-20(diazoxide:-20young,-205.1-20±-200.2-20nS-3B-20aged,-203.5-20±-200.5-20nS,-20P-20-3C-200.01),-20resulting-20in-20a-20∼2.8-20mM-20left-20shift-20in-20the-20β-20cell-20glucose-20threshold.-20Our-20results-20demonstrate-20how-20mice,-20but-20not-20humans,-20are-20able-20to-20successfully-20compensate-20for-20age-2Dassociated-20metabolic-20dysfunction-20by-20adjusting-20their-20β-20cell-20glucose-20sensitivity,-20and-20highlight-20an-20essential-20mechanism-20for-20ensuring-20the-20maintenance-20of-20insulin-20secretion.-0A-0A©-202016-20by-20the-20American-20Diabetes-20Association.-20Readers-20may-20use-20this-20article-20as-20long-20as-20the-20work-20is-20properly-20cited,-20the-20use-20is-20educational-20and-20not-20for-20profit,-20and-20the-20work-20is-20not-20altered." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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