Mitochondrial malfunction mediates impaired cholinergic Ca < sup > 2+ < /sup > signalling and submandibular salivary gland dysfunction in diabetes

In this study, we show that diabetic animals exhibit severe xerostomia, evident by reduced saliva flow rate, diminished total protein content, and decreased amylase activity in the saliva secreted by submandibular glands. These impairments remained resistant to exogenous cholinergic stimulation. In submandibular acinar cells in diabetes, the intracellular Ca2+ signals evoked by cholinergic stimulation were reduced and delayed, caused by malfunctioning mitochondria. Upon initiation of cholinergic-evoked Ca2+ signals, mitochondria accumulate higher Ca2+ and fail to redistribute Ca2+ influx and facilitate the store-operated Ca2+ entry effectively. Structural damage to mitochondria was evident in the acinar cells in diabetes. These findings provide insights into the potential targeting of malfunctioning mitochondria for the treatment of diabetic xerostomia as an alternative strategy to the existing pharmacotherapeutic approaches.PMID:37972885 | DOI:10.1016/j.neuropharm.2023.109789
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Source Type: research