Role of insulin on jejunal PepT1 expression and function regulation in diabetic male and female rats

Abstract

The aim of this study was to determine whether the jejunal oligopeptide transporter PepT1 is regulated by insulin and whether this regulation is sex-dependent in type 1 diabetic rats. PepT1 expression, real-time polymerase chain reaction, and Western blots were performed using jejunal segments from 4 groups of male and female rats: normal (nondiabetic), insulin-treated nondiabetic, streptozotocin (STZ)-induced diabetic (type 1 diabetes), and insulin-treated diabetic models. Furthermore, the same segments from all groups underwent perfusion to assess uptake of the dipeptide glycylsarcosine through PepT1. Our results showed that insulin treatment of nondiabetic female rats decreased blood glucose level but did not affect nondiabetic male rats. In both male and female diabetic rats, insulin did not completely decrease blood glucose level. Insulin treatment decreased PepT1 mRNA level in nondiabetic male rats and increased mRNA level in nondiabetic female rats without affecting the PepT1 protein level in either sex. Inducing diabetes with STZ increased PepT1 mRNA and protein levels in female rats; however, in diabetic male rats, the increase in mRNA level was accompanied by a decrease in PepT1 protein level. Treatment of diabetic male rats with insulin partially reversed the effect of diabetes on PepT1 mRNA and protein levels, whereas the same treatment completely restored both PepT1 mRNA and protein to control levels in insulin-treated diabetic female rats. In both nondiabetic male and female rats, insulin treatment had no effect on PepT1 influx rate, and STZ treatment decreased the transporter influx rate. Treatment of diabetic male and female rats with insulin significantly increased PepT1 influx rate; however, complete recovery was found only in diabetic female rats. These results clearly show that insulin and diabetes affected blood glucose level as well as PepT1 activity, expression, and protein levels in a sex-dependent manner. These results suggest that a factor, probably estrogen, could be responsible for the sex-dependent effects of diabetes and insulin in PepT1 level and activity.

The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells

“…Interestingly, two mRNAs enriched in MetS-EVs were also enriched in MetS-MSCs, as we observed in a recent study [ 25 ]. The nuclear receptor subfamily-5 group-A member-1 (NR5A1, or steroidogenic factor-1), which modulates the expression of insulin-like factor 3, relaxin-like factor [ 48 ], and the oligopeptide transporter PepT1 solute carrier family-15 member-1 (SLC15A1), which is highly regulated by insulin [ 49 ]. These observations suggest that MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSCs and their daughter EVs.…”

Immunogenetic control of the intestinal microbiota

“…Environmental factors including diet and infections probably modulate the abundance of specific taxa within the microbial ecosystem. Expression of the intestinal peptide transporter PEPT 1 is modified by oestrogen, so providing sex‐specific effects. The GPI ‐anchors are the major target of signalling via GPI ‐anchored proteins.…”

Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

“…Importantly, altered expression and function of intestinal PepT1 are also dependent on sex. For example, in Sprague-Dawley rats, it was reported that STZ-induced diabetes decreased the expression and function of intestinal PepT1 in male rats, but increased them in female rats [100]. Leptin and insulin deficiencies may contribute to the downregulation of intestinal PepT1 [101,102].…”