Different Effect of Handle Region Peptide on β-Cell Function in Different Sexes of Rats Neonatally Treated with Sodium L-Glutamate

Abstract

BackgroundThe (pro)renin receptor ((P)RR) was reported to be expressed in various tissues including the pancreas, and handle region peptide (HRP) is believed to block the function of (P)RR. This study aimed to investigate the effect of HRP on the glucose tolerance status and β-cell function of female rats, neonatally treated with sodium L-glutamate (MSG) and to compare with the previously reported HRP effect on male rats.Material/MethodsFemale MSG rats aged 8 weeks were divided into MSG control group and HRP treated group and the normal SD rats served as control. The MSG rats were treated with HRP by osmotic minipumps with dose of 1 mg/kg per day for total 28 days. Glucose tolerance status was evaluated at the end of the study. Islets α-cell and β-cell were marked with insulin antibody and glucagon antibody respectively. The proliferation of islet cells and expression of subunit of NADPH oxidase P22phox were marked by PCNA and P22phox antibody. Picrosirius red staining was performed for evaluating fibrosis of islets.ResultsHRP improved the glucose status tolerance with decreasing α-cell mass, islets PCNA-positive cells, expression of P22phox and picrosirius red stained areas, and increasing β-cell mass in female MSG rats. The indexes with obviously interacted effect of sexes and HRP for the MSG rats were the AUC of blood glucose concentration (P<0.01), α-cell mass (P<0.05), proliferation of islet cells (P<0.01) and area of picrosirius red staining (P<0.01).ConclusionsHRP improved the glucose tolerance status in the females although it was previously reported to worsen the glucose tolerance in male MSG rats. Different levels of sex hormones may partly account for the disparate effects observed for HRP in different sexes.

A New Way for Beta Cell Neogenesis: Transdifferentiation from Alpha Cells Induced by Glucagon-Like Peptide 1

“…The number of PCNA-positive cells in each islet section was counted under a microscope. Three islets were randomly selected for analysis in each rat [ 17 ].…”

Immunohistochemistry for (Pro)renin Receptor in Humans

“…Low levels of (P)RR mRNA expression are observed in the human pancreas [ 1 ]. In rats, the (P)RR participates in the pathogenesis of glucose intolerance, at least in part through RAS-dependent mechanisms [ 26 , 27 ]. In addition, the a3 isoform of the V-ATPase has been shown to be expressed in the islets of Langerhans and to have a pivotal role in the regulation of insulin exocytosis from pancreatic β -cells in mice [ 28 ].…”