Morphometric Study of Diabetes Related Alterations in Human Parotid Gland and Comparison with Submandibular Gland

Lilliu, Maria Alberta; Loy, Francesco; Cossu, Margherita; Solinas, Paola; Isola, Raffaella; Isola, Michela

doi:10.1002/ar.23255

Cited by 16 publications

(10 citation statements)

References 43 publications

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“…These findings strongly suggest differences among the three glands in the apical membrane dynamics in which PIPKα is involved, indicating that the three salivary glands are discrete not only in histology but also in secretory activity, as recently noted (Isola & Lilliu, ; Lilliu et al. ).…”

Section: Discussionsupporting

confidence: 80%

“…are discrete not only in histology but also in secretory activity, as recently noted (Isola & Lilliu, 2015;Lilliu et al 2015). Although this is the first report of PIP5Ka activity confined to the acinar cells in salivary glands, several studies have reported the apical plasmalemmal localization of endogenous PIP5Ka and b in cultured renal collecting tubular cells, another polarized epithelial cell type similar to the glandular acinar cells (Weixel et al 2007;Szalinski et al 2013).…”

Section: Discussionsupporting

confidence: 64%

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Localization of phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K) α, β, γ in the three major salivary glands in situ of mice and their response to β‐adrenoceptor stimulation

et al. 2019

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Phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K), which is composed of three isozymes (α, β and γ), catalyzes the production of phosphatidylinositol bisphosphate (PIP2). This phospholipid functions in membrane trafficking, as an anchor for actin cytoskeletons and as a regulator of intramembranous channels/transporters. It is also a precursor of such second messengers as diacylglycerol, inositol triphosphate and phosphatidylinositol (3,4,5)‐triphosphate. In the present study, the expression and localization of endogenous PIP5Ks were examined in the three major salivary glands of young adult mice in situ. In western blotting of normal control glands, immunoreactive bands for individual PIP5Ks were detectable, with the highest density in the parotid gland and the weakest density in the submandibular gland. In immuno‐light microscopy under non‐stimulated condition, weak immunoreactivity for PIP5Kα was confined to the apical plasmalemma in parotid, but not sublingual or submandibular, acinar cells. Immunoreactivity for PIP5Kβ was weak to moderate and confined to ductal cells but not acinar cells, whereas that for PIP5Kγ was selectively and intensely detected in myoepithelial cells but not acinar cells, and it was weak in ductal cells in the three glands. In western blot of the parotid gland stimulated by isoproterenol, a β‐adrenoceptor agonist, no changes were seen in the intensity of immunoreactive bands for any of the PIP5Ks. In contrast, in immuno‐light microscopy, the apical immunoreactivity for PIP5Kα in parotid acinar cells was transiently and distinctly increased after the stimulation. The increased immunoreactivity was ultrastructurally localized on most apical microvilli and along contiguous plasma membrane, where membranous invaginations of various shapes and small vesicles were frequently found. It was thus suggested that PIP5Kα is involved in post‐exocytotic membrane dynamics via microvillous membranes. The present finding further suggests that each of the three isoforms of PIP5K functions through its product PIP2 discretely in different cells of the glands to regulate saliva secretion.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 64%

Localization of phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K) α, β, γ in the three major salivary glands in situ of mice and their response to β‐adrenoceptor stimulation

et al. 2019

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“…At first sight, these results might be suggestive of increased melatonin secretion, in the event of selective exocytosis of these granules. However, considering the results of our recent morphometric investigation, an alternative interpretation can be proposed (Lilliu et al, , ). We suggest that in the diabetic condition, granule emptying is hampered, probably because the granules cannot fuse with the luminal membrane and hence are unable to discharge their content in the lumen of the gland.…”

Section: Discussionmentioning

confidence: 97%

“…In addition, the morphology of the parotid and submandibular glands is differently affected in diabetes. Acinar size and granule area were significantly increased in diabetic submandibular glands compared to non‐diabetic submandibular glands, whereas both parameters remained unaltered in diabetic parotid samples (Lilliu et al, , ). The present findings provide evidence that parotid and submandibular glands differ from each other in their susceptibility to alterations related to diabetes as well as to other pathologies.…”

Section: Discussionmentioning

confidence: 99%

Diabetic Status Influences the Storage of Melatonin in Human Salivary Glands

Isola

Lilliu

Loy

et al. 2017

The Anatomical Record

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Recently we reported on the detailed localization of melatonin (and its receptors) in human salivary glands, revealing that serous cells are able to store and secrete melatonin into saliva. Since we found that type 2 diabetic patients display reduced melatonin content in saliva, our next step was to examine the presence of melatonin in salivary glands removed from type 2 diabetic subjects. The resulting data were compared with those previously obtained by identical procedures in non-diabetics, to establish if the diabetic status may affect melatonin distribution. Bioptic samples of diabetic parotid and submandibular glands were fixed, dehydrated, embedded in Epon Resin and processed to demonstrate melatonin reactivity by the immunogold staining method. The labeling density (expressed as the number of gold particles per μm /granule) and the percentage of melatonin-positive granules were assessed in diabetic samples. These values were compared with those in non-diabetic samples and differences were evaluated. In parotid and submandibular diabetic glands the reactivity for melatonin was specifically associated with secretory granules and small vesicles in serous cells. Melatonin reactivity was higher in parotid than in submandibular glands. Our data were in line with those obtained in our previous study on non-diabetic glands. Diabetic salivary glands showed a higher labeling density and a lower number of melatonin-positive granules compared to non-diabetic glands. Taken together, these data might explain the decreased salivary melatonin content and the associated oral problems observed in diabetics. Anat Rec, 301:711-716, 2018. © 2017 Wiley Periodicals, Inc.

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“…This finding indicates that, among the major salivary glands, parotid is the most involved in melatonin release. It is noteworthy that the degree of participation to melatonin supply represents a further feature distinguishing the salivary glands from one another, in addition to many anatomical, embryonic, histochemical and metabolic diversities .…”

Section: Discussionmentioning

confidence: 99%