Nuclear factor-κB and advanced glycation end-products expression in lacrimal glands of aging rats

Advanced glycation end products (AGEs) increase with aging and induce signaling alterations that lead to inflammation and dysfunction in several tissues. Aging reduces function and insulin signaling in lacrimal glands (LGs). To evaluate whether AGE signaling and insulin secretion it] LGs are altered in aging, 24- and 2-month-old male Wistar rats were compared. Immunohistochemistry with confocal microscopy was used to evaluate AGE, AGE receptor (RAGE) and nuclear factor-kappa B (NF-kappa B) expression in LGs. Basal tear secretion volume, insulin, interleukin-1 beta (IL-1 beta) and minor necrosis factor-alpha. (TNF-alpha) levels in tears and LGs and peroxiclase activity in LG tissue were measured. Insulin secretion from isolated LGs and pancreatic P-cells was compared in the supernatant of aging and control rats in vitro by RIA after stimulation with 2 center dot 8-16 center dot 7 mM glucose, carbachol and KCl. AGE, RAGE and NF-kappa B expression was higher in LGs of aging compared with young rats. Basal tear secretion and peroxidase activity were significantly lower in the aging group (P = 0 center dot 016 for both assays). IL-1 beta and TNF-a levels were higher in tears of aging rats compared with young rats (P = 0 center dot 007 and 0 center dot 05 respectively); however, even though aging rats were insulin-resistant (as confirmed by the insulin-tolerance test), the insulin levels in the tear film of aging and control rats were similar in vivo and in vitro. The higher expression of AGEs, RAGE and NF-kappa B in LGs of aging rats is accompanied by systemic insulin resistance and may be involved in LG and tear film alterations but does not affect insulin secretion in the tear film. These observations indicate that metabolic events may be related to LG and tear film dysfunctions in aging.