The protein nucleobindin-2 (NUCB2, also known as nesfatin) was recently implicated as a mediator of anorexia and catabolism in the central nervous system, and has been suggested to act as a cleaved and secreted messenger. Given the overlap of signalling molecules between the brain and pancreas, we have explored the presence of NUCB2 in the islets of Langerhans. We also performed an investigation of the dynamic regulation of pancreatic NUCB2 in different metabolic states. NUCB2-like immunoreactivity was detected by immunofluorescence in all human and rat islet b-cells (as detected by co-localization with insulin), but not in other islet cells or in the exocrine pancreas. Islet NUCB2 content, as measured by enzyme immunoassay, did not change significantly following an overnight fast, but was substantially lower in islets isolated from an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rats (48% of non-diabetic Wistar rat control). Serum levels, however, were not different between Wistar and GK rats. The release of NUCB2 from isolated rat islets was significantly elevated following glucose challenge (123%), but this effect was substantially lower than that observed for insulin (816%). In contrast, serum levels of NUCB2 showed a reversible decrease in an i.p. glucose tolerance test. These data suggest a role for NUCB2 in b-cell function and a potential involvement in diabetic pathology. However, our findings, together with previous reports, appear more compatible with intracellular actions rather than with endocrine/paracrine communication, and suggest that NUCB2 in serum derives primarily from non-islet sources.
The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI.
Epidemiological data imply a role of estrogen in the pathogenesis of urinary tract infections (UTIs), although the underlying mechanisms are not well understood. However, it is thought that estrogen supplementation after menopause decreases the risk of recurrent infections. We sought to investigate the influence of estrogen on host-pathogen interactions and the consequences for UTI pathogenesis. We analyzed urothelial cells from menstruating and postmenopausal women before and after a 2-week period of estrogen supplementation, and also studied the influence of estradiol during Escherichia coli UTI in a mouse infection model. Important findings were confirmed in two human urothelial cell lines. We identified two epithelial defense mechanisms modulated by estrogen. Estrogen induced the expression of antimicrobial peptides, thereby enhancing the antimicrobial capacity of the urothelium and restricting bacterial multiplication. In addition, estrogen promoted the expression and redistribution of cell-cell contact-associated proteins, thereby strengthening the epithelial integrity and preventing excessive loss of superficial cells during infection. These two effects together may prevent bacteria from reaching deeper layers of the urinary tract epithelium and developing reservoirs that can serve as a source for recurrent infections. Thus, this study presents some underlying mechanisms for the beneficial effect of estradiol after menopause and supports the application of estrogen in postmenopausal women suffering from recurrent UTI.
Material Supplementary 8.DC1http://www.jimmunol.org/content/suppl/2010/02/01/jimmunol.080435References
SummaryMajor long-term complications in patients with diabetes are related to oxidative stress, caused by the hyperglycaemia characteristic for diabetes mellitus. The anti-oxidant coenzyme Q10 (CoQ10) has therefore been proposed as a beneficial supplement to diabetes treatment. Apart from its anti-oxidative function, CoQ10 appears to modulate immune functions by largely unknown mechanisms. The aim of this study was therefore to investigate the effect of CoQ10 on antimicrobial peptides and natural killer (NK) cells, both innate immune components implicated in the pathogenesis of diabetes and diabetes-associated long-term complications such as cardiovascular disease. We determined serum levels of antimicrobial peptides and the phenotype of NK cells isolated from peripheral blood of patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and from healthy controls. In addition, the same parameters were determined in diabetic patients after a 12-week period of CoQ10 supplementation. Two antimicrobial peptides, the human cathelicidin antimicrobial peptide (CAMP) and the human beta defensin 1 (hBD1), were reduced in serum from patients with T1DM. This defect was not reversible by CoQ10 supplementation. In contrast, CoQ10 reduced the levels of circulating hBD2 in these patients and induced changes in subset distribution and activation markers in peripheral NK cells. The results of the present study open up novel approaches in the prevention of long-term complications associated to T1DM, although further investigations are needed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.