INS and Hyperglycemia: The progression of β-cell dysfunction includes not only defective insulin secretion but also β-cell mass reduction, which results from β-cell apoptosis, the failure of existing β cells to proliferate, and β-cell dedifferentiation under metabolic stress such as hyperglycemia, hyperlipidemia and chronic inflammation (Sun and Han, 2020; Ying et al., 2020; Amo-Shiinoki et al., 2021).