Does Zn-Mediated Regulation of the Kynurenine Pathway Provide the Link Between Periodontal Disease and Diabetes?

It has long been known that there is a relationship between periodontal diseases and diabetes. The present study aimed to assess the effect of pancreatic zinc (Zn) levels on Kynurenin pathways (KP) and glucose homeostasis and the impact of Thymoquinone (TQ) in the periodontal disease animal model. Ten microliters of Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-Lps) (1 mg/ml) was injected at 48-h intervals into the palatal gingiva of rats, and TQ was given by oral gavage (10 mg/kg per day) for 2 weeks. Glucose homeostasis was assessed using the Homeostatic Model Assessment (HOMA-IR), and β-cell function (HOMA-β Levels). Kynurenine (KYN), Tryptophan (TRP), kynurenic acid (KYNA), quinolinic acid (QA), KYN 3-monooxygenase (KMO), kynureninase, interferon-γ (IFN-γ), insulin, ZIP10, and caspase-3 levels measured by the enzyme-linked immunosorbent assay (ELISA). Zinc levels in the pancreas tissue and plasma samples were measured using a colorimetric method. Morphological changes in the pancreas were identified by hematoxylin and eosin staining, and X-ray radiography determined bone resorption in the maxillary bone. In the LPS group, pancreas ZIP10 and Zn levels increased, the KP pathway was altered to favor KYNA, and impaired glucose homeostasis was observed. TQ administration decreased pancreatic Zn levels, changed KP to favor QA, and improved morphological changes in the pancreas. During the progression of periodontal diseases, KP may be altered by Zn levels through ZIP10 in the pancreas, thereby impairing pancreatic function. Regulation of Zn levels may be key to shared pathways between periodontal diseases and diabetes.