A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets

Abstract

BackgroundGap junctions between β-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between β-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1–15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls.ResultsThe low-protein diet reduced the levels of connexin 36 and β-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser279/282]-connexin 43, and it decreased the levels of connexin 36, β-catenin and beta-actin mRNA as well as the levels of connexin 36 and β-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser279/282]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status.ConclusionShort-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion.

The role of adherens junction proteins in the regulation of insulin secretion

“…It is also interesting to note that the reductions in GSIS that are induced by treatment with the anti-depressant drug fluoxetine (Prozac) [ 61 ] are also associated with decreases in E-cadherin levels in β-cells [ 62 ]. It has also been observed that mice on a low protein diet have reductions in GSIS that correlate with reductions in β-catenin levels in islets [ 63 ]. We see rapid changes in β-catenin levels in β-cell models in response to acute changes in glucose levels [ 41 ], which could provide a mechanism that would allow glucose levels to regulate the maximum levels of GSIS over the time frame of minutes and hours.…”

Pregnancy‐induced changes in β‐cell function: what are the key players?

“…2005; Marçal‐Pessoa et al . 2015). The same diet during pregnancy also reduced maternal islet area in association with reduced PI3K signalling, but no change in insulin content was observed (Salvatierra et al .…”