Figure 2. Summary of the regulation of insulin secretion during the course of aging process. Thyroid hormone (T3) promotes β cell functional maturation via the induction of MafA expression along with p16Ink4a activation at the early stage of aging. During the progression of aging process, impaired mitochondria function causes KATP channel shutting down and Ca2+ influx at the same time, thereby enhancing insulin secretion in a short time frame. In contrast, during the advanced aging process, β cells manifest diminished expression of senescence marker protein-30 (SMP-30) along with deoxysphingolipid accumulation, thereby impeding insulin secretion through unknown mechanisms.