INS and Hyperglycemia: Glucose-stimulated insulin secretion (GSIS) is compromised in diabetes, which, in part, leads to the long-term hyperglycemia condition first proposed by Unger et al. in the 1980s as “glucotoxicity” (Unger and Grundy, 1985; Ostenson and Efendic, 2007; Bensellam et al., 2012).