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

The phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways mediate ß 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 (p70S6K), 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.

Soybean diet alters the insulin-signaling pathway in the liver of rats recovering from early-life malnutrition.

OBJECTIVE: We investigated if alterations in the insulin-signaling pathway could contribute to reduced hepatic glycogen levels in adult rats subjected to a protein deficiency during intrauterine life and lactation and reared through to recovery on a soybean diet. METHODS: Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with a 17% casein diet (offspring born to and suckled by mothers fed a control diet and subsequently fed the same diet after weaning [CC group] and offspring born to and suckled by mothers fed a control diet and subsequently fed a soybean flour diet with 17% protein after weaning [CS group]), a soybean diet (offspring of mothers fed a low-protein diet and a control diet after weaning [LC group] and offspring of mothers fed a low-protein diet and fed a soybean flour diet containing 17% protein after weaning [LS group]), or a 6% casein diet (offspring of mothers fed a low-protein diet and subsequently fed the same diet after weaning [LL group]) from weaning until 90 d of life. RESULTS: A soybean diet did not modify basal serum glucose and glucagon concentrations, but raised basal serum insulin and consequently increased the serum insulin/glucose ratio. Insulin receptor and insulin receptor substrate-1 levels were lower in rats fed a soybean diet compared with those maintained with a casein diet. In the LS group, the p85 levels were higher than in the LC group, whereas in CS rats its expression was lower than in CC rats. The expression of p110 was lower in the CS group compared with the CC group and similar in the LS and LC groups. Insulin receptor substrate-1 phosphorylation was similar in the LS, LC, and CS groups and lower compared with the CC group. The insulin receptor substrate-1-p85/phosphatidylinositol 3-kinase association was lower in LS than in LC rats and in CS than in CC rats. Akt phosphorylation was lower in the CS and LS groups than in the CC and LC groups. CONCLUSION: Adult rats maintained with a soybean diet exhibited insulin resistance due, at least in part, to alterations in the early steps of the insulin signal transduction pathway.

Soybean diet modulates acetyl-coenzyme A carboxylase expression in livers of rats recovering from early-life malnutrition.

OBJECTIVE: The present study evaluated the effect of nutritional recovery with a soybean diet on the gene and protein expressions and protein phosphorylation of several enzymes and transcription factors involved in hepatic lipid metabolism. METHODS: Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with a 17% casein (CC and LC groups) or soybean (CS and LS groups) diet and with a 6% casein (LL group) diet until 90 d of life. RESULTS: The soybean diet enhanced serum insulin levels but decreased body and liver weights and hepatic lipid and glycogen concentrations. Liver peroxisome proliferator receptor-alpha mRNA abundance was higher in the LS and CS groups than in the LC and CC groups, but the protein content was similar in all groups. Hepatic acetyl-coenzyme A carboxylase (ACC)-alpha and ACCbeta mRNA expression was markedly lower in the LS and CS rats than in the LC and CC rats. ACC protein expression was lower in the CS group than in the CC, LC, and LS groups. Phospho-[Ser(79)]2-ACC content was similar in the CS, LC, and LS groups and lower than the CC group. In the CS rats this reduction paralleled the decrease in total ACC protein. Messenger RNA and protein expression of sterol regulatory element-binding protein 1c, adenosine monophosphate-activated protein kinase, and phospho-[Thr(172)]-adenosine monophosphate-activated protein kinase was not modified by the soybean diet. CONCLUSION: Thus, the soybean diet reduced the liver lipid concentration through downregulation of the ACC gene and protein expressions rather than by phosphorylation status, which possibly resulted in decreased lipogenesis and increased beta-oxidation.