Functional maturation of immature β cells: A roadblock for stem cell therapy for type 1 diabetes

Figure 2 Relationship between mTORC1 and AMPK in the process of β cell transformation from immature to mature. Immediately after birth, the nutritional substrates are mainly amino acids, which activate the nutritionally sensitive mTORC1 and promote cell proliferation. mTORC1 is inhibited by AMPK and upstream regulatory factors TSC1/TSC2. When the nutritional substrate changes from amino acids to glucose, AMPK activity is stimulated. AMPK is activated by the upstream factor LKB1 under the regulation of intracellular ratio of ATP vs AMP/ADP, inhibits β cell proliferation, and promotes maturation, resulting in the establishment of adult-type glucose stimulated insulin secretion.