Protein restriction in early life increases intracellular calcium and insulin secretion, but does not alter expression of SNARE proteins during pregnancy

New findings: What is the central question of this study? Does protein restriction in early life modify glucose-induced insulin secretion by altering [Ca²⁺ ]_i and the expression of SNARE proteins in pancreatic islets from pregnant rats? What is the main finding and its importance? Protein restriction in early life increased the first phase of glucose-induced insulin secretion and [Ca²⁺ ]_i without altering the expression of SNARE proteins during pregnancy. This finding contributes to our understanding of the mechanisms of altered insulin secretion and might provide new perspectives for the development of therapeutic tools for gestational diabetes.

Abstract: We investigated the kinetics of glucose-induced insulin secretion and their relationship with [Ca²⁺ ]_i and the expression of protein from exocytotic machinery in islets from recovered pregnant and long-term protein-deficient pregnant rats. Isolated islets were evaluated from control-fed pregnant (CP), protein-deficient pregnant (DP), control-fed non-pregnant (CNP) and protein-deficient non-pregnant (DNP) female adult rats, and from protein-deficient pregnant (RP) and non-pregnant (RNP) rats that were recovered after weaning. The insulin responses to glucose during the first phase of secretion were higher in RP than in CP groups, and both were higher than in the DP group. Islets from RP rats displayed a rapid increase in insulin release (first phase), followed by a plateau that was maintained thereafter. The [Ca²⁺ ]_i in islets from the protein-deficient groups was lower than in the control groups, and both were lower than in the RP and RNP groups. SNAP-25 was increased in islets from pregnant rats independently of their nutritional status, and the syntaxin-1A content was reduced in islets from the RP rats compared with the RNP rats. The VAMP2 content was similar among the groups. Thus, protein restriction during intrauterine life and lactation increased insulin secretion during pregnancy, attributable, in part, to increased [Ca²⁺ ]_i , and independent of an alteration of expression of SNARE proteins.