Handle Region Peptide Ameliorating Insulin Resistance but NotβCell Functions in Male Rats Neonatally Treated with Sodium L-Glutamate

Abstract

Handle region peptide (HRP), which was recognized as a blocker of (pro)renin receptor ((P)RR), may block the function of (P)RR. The aim of this study was to investigate the effect of HRP with a large dose of 1 mg/kg/d on glucose status in the rats treated neonatally with monosodium L-glutamate (MSG). At the age of 8 weeks, the MSG rats were randomly divided into MSG control group, HRP treated group with minipump (MSG-HRP group), losartan treated group (MSG-L group), and HRP and losartan cotreated group (MSG-HRP-L group) and fed with high-fat diet for 4 weeks. Losartan but not HRP increased the levels of insulin releasing and ameliorate glucose status although both losartan and HRP improved insulin sensitivity. On the one hand, both losartan and HRP decreased levels of pancreatic local Ang-II and NADPH oxidase activity as well as its subunits P22phox. On the other hand, losartan but not HRP decreased α-cell mass and number of PCNA-positive cells located periphery of the islets and decreased picrosirius red stained area in islets. HRP ameliorating insulin resistance but not β-cell functions leads to hyperglycemia in the end in male MSG rats, and the dual characters of HRP may partly account for the phenomenon.

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

“…Two-way ANOVA analysis was performed to make sense of the interacted effect of sexes and HRP for the MSG rats (the results of the male rats have been published before [ 12 ]). 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).…”

“…Neonatal female rats were injected subcutaneously with either 4 mg/g of MSG (Sigma Aldrich, Mo, USA) or NaCl(1.87% solutions) as control (Con group) at age of 2, 4, 6, 8, and 10 days. The experiments about the male rats were conducted at the same time and the results were published before [ 12 ]. All of the animals were weaned at age of 3 weeks.…”

“…The neuronal loss impairs insulin and leptin signaling and impacts the energy balance [ 7 – 11 ]. We previously reported that functions and structures of islets in MSG rats are abnormal, and that losartan improves the islet function [ 12 ].…”

“…Recent clinical data also showed that prevalence of type 2 diabetes is lower in premenopausal women, especially diabetic syndromes with insulin deficiency, suggesting that the female hormone 17β-estradiol protects pancreatic β-cell function and may constitute an important regulator of glucose metabolism and homeostasis [ 13 – 16 ]. We previously reported that HRP improved insulin sensitivity but not β-cell function and lead to hyperglycemia in male rats neonatally treated with MSG [ 12 ]. This study aimed to report the effect and mechanisms of HRP on the glucose tolerance status in female rats neonatally treated with MSG and to compare these effects to previously published data obtained for HRP in male MSG rats.…”

Monosodium glutamate affects cognitive functions in male albino rats

“…The administration of MSG to newborn rats results in distinctive lesions in hypothalamic arcuate nucleus neurons. The neuronal loss impairs insulin and leptin signaling and impacts energy balance as well as pituitary and adrenal activity (Yin et al, 2013).These effects are mostly attributed to immaturity of blood brain barrier in those young animals (Boonnate et al, 2015).…”