Association of Bactericidal Dysfunction of Paneth Cells in Streptozocin-Induced Diabetic Mice with Insulin Deficiency
Tao Yu, Hong-Sheng Yang, Xi-Ji Lu, Zhong-Sheng Xia, Hui Ouyang, Ti-Dong Shan, Can-Ze Huang, Qi-Kui Chen
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland)
Med Sci Monit 2016; 22:3062-3072
Type 1 diabetes mellitus (T1DM) is associated with increased risks of enteric infection. Paneth cells constitute the first line of the gut defense. Little is known about the impact of T1DM on the bactericidal function of intestinal Paneth cells.
MATERIAL AND METHODS: A T1DM mouse model was induced by intraperitoneal injection of streptozocin. The analysis of intestinal microbiota and the mucosal bactericidal assay were conducted to evaluate intestinal innate defense. Numbers of Paneth cells and their expression of related antimicrobial peptides were analyzed. Expression of total insulin receptor (IR) mRNA and relative levels of IR-A/IR-B were analyzed. The primary mouse small intestinal crypt culture was used to analyze the effect of insulin and glucose on the expression of related antimicrobial peptides of Paneth cells.
RESULTS: In T1DM mice, bacterial loads were increased and there was an alteration in the composition of the intestinal microflora. Exogenous bacteria had better survival in the small bowel of the T1DM mice. The expression of Paneth cell-derived antimicrobial peptides was significantly decreased in the T1DM mice, although the number of Paneth cells was increased. Relative levels of IR-A/IR-B in Paneth cells of diabetic mice were elevated, but the total IR mRNA did not change. Insulin treatment restored the expression of antimicrobial peptides and normalized the microbiota in the gut of T1DM mice. Subsequently, in vitro culture assay demonstrated that insulin rather than glucose was essential for the optimal expression of Paneth cell-derived antimicrobial peptides.
CONCLUSIONS: The bactericidal function of intestinal Paneth cells was impaired in STZ-induced diabetic mice, resulting in the altered intestinal flora, and insulin was essential for the optimal expression of Paneth cell-derived antimicrobial peptides.
Keywords: Antimicrobial Cationic Peptides - immunology, Animals, Diabetes Mellitus, Experimental - microbiology, Diabetes Mellitus, Type 1 - microbiology, Immunity, Innate, Insulin - deficiency, Intestinal Mucosa - microbiology, Intestine, Small - microbiology, Mice, Mice, Inbred C57BL, microbiota, Paneth Cells - microbiology, Random Allocation, Receptor, Insulin - metabolism