Mechanisms controlling postnatal maturation of pancreatic beta cells

The crucial metabolic hormone insulin, which is produced and secreted exclusively by pancreatic beta cells, serves different roles before and after birth: prenatally it acts primarily as a growth factor, whereas postnatally it is essential for maintaining carbohydrate and lipid homeostasis. Accordingly, at birth a dramatic switch occurs in beta cell nutrient sensitivity, converting them from an amino acid-responsive state to glucose-responsive. Previous results (Helman et al, 2020) demonstrated that this switch involves altered signaling of the mTORC1 pathway. In order to better understand the mechanisms underlying this transition, we determined responsiveness to nutrients in the immediate post-natal period (days P1-P5). Consistent with previous observations, we found that whereas neonatal P1 islets respond to elevated amino acids with increased phosphorylation of ribosomal protein S6 (p-S6) and insulin secretion, they showed little or no response to elevated glucose. With increasing age (P3 and P5) there is a gradual loss of responsiveness to amino acids, and gain of responsiveness to glucose. Interestingly, amino acid responsiveness seems to be lost before glucose responsiveness is acquired, suggesting that distinct molecular mechanisms may be involved. A better understanding of the mechanisms underlying this critical transition may help shed light on the underlying causes of diabetes and its complications.