Nobiletin, an agonist of the core-clock proteins RORα/γ, boosted both circadian amplitude of T2DM islet clocks and insulin secretion by these islets [76]. Nobiletin increased islet circadian clock amplitude and augmented glucose-stimulated insulin secretion (GSIS) in isolated human islets in a Bmal1-dependent manner [77]. Here, INS is linked to type 2 diabetes mellitus.