The effects of ageing and streptozotocin (STZ) - induced diabetes mellitus on the rodent parotid gland

Mahay, Sukhbinder Kumar (2005) The effects of ageing and streptozotocin (STZ) - induced diabetes mellitus on the rodent parotid gland. Doctoral thesis, University of Central Lancashire.

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Xerostomia (dryness of the mouth) is a prevalent condition amongst elderly and diabetic populations which leads to marked alterations in oral health. The parotid glands play major roles in maintaining salivary secretions to assist in the lubrication
and protection of the oral cavity and in digestion. This study investigated the effects of ageing and streptozotocin (STZ)-induced diabetes on the structure and function of the rat parotid gland. Rats (2-6, 12, 16-18 and 22-24 months old) were obtained from a recommended Home Office supplier and diabetic rat models were achieved by employing STZ. The results showed that aged glands were disorganised and infiltrated with connective tissues, lipid droplets and mast cells compared to younger control glands. A significant (P<0.05) reduction in the mean acinar cell number was also observed in aged glands. Parotid glands taken from STZ-induced diabetic rats showed extensive infiltration of lipid droplets when compared to glands of agematched control rats. Acetylcholine (ACh), noradrenaline (NA) or isoprenaline (ISOP) elicited marked increases in amylase release from parotid acini of 2-6 month old (control) rats. However, this amylase release was significantly (Pc0.05) reduced in parotid acini of 12, 16-18 and 22-24 month old rats. In parotid segments of STZinduced diabetic rats, both ACh and NA (1xl0 5 M for both) evoked a significant (P<0.05) reduction in amylase secretion when compared to responses obtained from age-matched control rats. Similarly, in parotid acini from STZ-induced diabetic rats, both ACh and NA induced the dose-dependent release of aniylase, but this response was significantly (Pc0.05) reduced compared to the results from age-matched control rats. In Fura-2-loaded parotid acinar cells, significant (Pc0.001) reductions in the peak and plateau phases of ACh-evoked Ca 2 signals (17340/17380) from parotid acinar cells isolated from animals aged 16-18 months were observed, compared to parotid acinar cells of 2-6 month old rats. In parotid acinar cells of STZ-induced diabetic rats
a significant (PcO.00l) reduction in only the plateau phases of the Ca 2 signals was observed, in 2.5 mM [Ca2 ]0. However, in 0 mM [Ca2 ]3 the plateau phase remained inhibited, but basal Ca2 signals were also reduced in parotid acinar cells of STZinduced diabetic rats, but not in parotid acinar cells of age-matched control rats. An elevation in the total Ca 2 concentration in whole gland segments from STZ-induced diabetic rats was also observed compared to age-matched control rats. Treatment of glands from 2-6 and 12 month old rats with .t-butyl hydroperoxide (tH202) resulted in marked time-dependent (2 and 4 Lu) increases in cytochrome c fluorescence, compared to untreated glands. In contrast, treatment of glands from 22-24 month old rats for the same time periods showed no apparent increases in cytochrome c compared to the other two age groups. Incubation of acini with either 0.5, 1 or 2 mM H202 resulted in significant (Pc0.05) increases in amylase release compared to basal levels in the absence of H202. In addition, stimulation of acini suspensions with either
ACh, NA or ISOP (1x10 7 M-lxlO4 M for all) resulted in the dose-dependent release of amylase above basal level. However, pretreatment of acini with 1 mM H202 followed by the addition of either ACh, NA or ISOP resulted in significant (Pc0.05)
decreases in amylase release compared to responses with secretagogues alone.
Analysis of acyl lipids showed that the TAGIPL ratio was significantly (PC0.01) higher in glands from aged animals compared to younger animals. Glands from STZinduced diabetic animals showed significant (P<0.05) alterations in total acyl lipid
profiles, 16:1/16:0 and 18:1/18:0 fatty acid ratios, relative proportions ofPL and TAG aèyl lipids and [ 14C] labelled TAG/PL ratios. The results of this study showed that both ageing and STZ-induced diabetes was associated with marked morphological and physiological changes in the rat parotid gland.

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