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Recent evidence has reignited the reconsideration of the established dogma that -cell dysfunction precedes hyperinsulinemia as some studies demonstrate hyperinsulinemia as an early, common event resulting from -cell dysfunction that leads to obesity and insulin resistance to initiate -cell exhaustion, ultimately leading to diabetes presentation (62)

Hofschroer V, Koch A, Ludwig F T, Friedl P, Oberleithner H, Stock C et al (2017) Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells