Short-term low-protein diet during pregnancy alters islet area and protein content of phosphatidylinositol 3-kinase pathway in rats

Abstract

The phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways mediate β cell growth, proliferation, survival and death. We investigated whether protein restriction during pregnancy alters islet morphometry or the expression and phosphorylation of several proteins involved in the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways. As controls, adult pregnant and non-pregnant rats were fed a normal-protein diet (17%). Pregnant and non-pregnant rats in the experimental groups were fed a low-protein diet (6%) for 15 days. Low protein diet during pregnancy increased serum prolactin level, reduced serum corticosterone concentration and the expression of both protein kinase B/AKT1 (AKT1) and p70 ribosomal protein S6 kinase (p70 S6K ), as well as the islets area, but did not alter the insulin content of pancreatic islets. Pregnancy increased the expression of the Src homology/collagen (SHC) protein and the extracellular signal-regulated kinases 1/2 (ERK1/2) independent of diet. ERK1/2 phosphorylation (pERK1/2) was similar in islets from pregnant and non-pregnant rats fed a low-protein diet, and was higher in islets from pregnant rats than in islets from non-pregnant rats fed a normal-protein diet. Thus, a short-term, low-protein diet during pregnancy was sufficient to reduce the levels of proteins in the phosphatidylinositol 3-kinase pathway and affect islet morphometry.

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

“…In addition, a 6% low protein diet fed to rats during pregnancy does not impact maternal glucose tolerance but is linked to reduced pancreatic islet abundance of proteins important for intercellular communication and coupled release of insulin by β-cells, including connexin 36 and β-catenin (Milanski et al 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 2015). Interestingly, pregnant female mice exposed to chronic protein restriction show reduced body weight, glucose intolerance, impaired β-cell GSIS and attenuation of the phospholipase C-protein kinase C signalling pathway that is involved in the insulin secretory process (Ignácio-Souza et al 2013;Szlapinski et al 2019).…”

“…This has involved using diets that contain anywhere between 6% casein and 23% casein as control. In rodents, intake of low protein diets containing 6-9% casein during pregnancy does not change the weight of the pregnant dam (Rutland et al 2007;Salvatierra et al 2015). However, a more minor reduction of dietary protein content (18% casein) in pregnant mice is associated with an increase in maternal hysterectomized body weight in late gestation, although whether this reflects an expansion of select tissues, lean and/or fat mass is unknown (Coan et al 2011).…”

“…2007; Salvatierra et al . 2015). However, a more minor reduction of dietary protein content (18% casein) in pregnant mice is associated with an increase in maternal hysterectomized body weight in late gestation, although whether this reflects an expansion of select tissues, lean and/or fat mass is unknown (Coan et al .…”

“…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 . 2015). Interestingly, pregnant female mice exposed to chronic protein restriction show reduced body weight, glucose intolerance, impaired β‐cell GSIS and attenuation of the phospholipase C–protein kinase C signalling pathway that is involved in the insulin secretory process (Ignácio‐Souza et al .…”

Morphometric Study of Changes in GAD 65 Expressing Beta Cell Mass In The Islets Of Langerhans In Pregnant Mice

“…13,14 Feeding rats a low-protein diet during pregnancy reduces pancreatic islet area, decreases circulating corticosterone levels and consequently, cellular proliferation, growth, survival and death. 15 The purpose of the present study was to assess the changes that might occur in the size, number and shape of β-cells of the pancreatic islets of pregnant mice using anti GAD65 Ab as a β-cell marker.…”