Disruption of tight junctions contributes to hyposalivation of salivary glands in a mouse model of type 2 diabetes

Abstract

Tight junction (TJ) plays an important role in regulating paracellular fluid transport in salivary glands; however, little is known about the involvement of TJs in diabetes salivary glands. This study aimed to investigate the alterations of TJs and their possible contribution in diabetes‐induced hyposalivation. Here, we observed that the morphologies of submandibular glands (SMGs) were impaired, characterized by enlarged acini accumulation with giant secretory granules, which were significantly reduced in atrophic ducts in SMGs of db/db mice, a spontaneous model of type‐2 diabetes. However, the secretory granules were increased and scattered in the acini of diabetes parotid glands (PGs). Other ultrastructural damages including swollen mitochondria, expansive endoplasmic reticulum, and autophagosomes were observed in the diabetes group. The levels of TJ proteins including claudin‐1 (Cldn1) and claudin‐3 (Cldn3) were increased, whereas those of claudin‐4 (Cldn4), occludin (Ocln), and zonula occludens‐1 (ZO‐1) were decreased in SMGs of db/db mice. Higher Cldn1 and Cldn3 and lower claudin‐10 (Cldn10) and Ocln levels were observed in PGs of diabetes mice. Taken together, the structures of SMGs and PGs were impaired in diabetes mice, and the disruption of TJ integrity in both SMGs and PGs may contribute to diabetes‐induced hyposalivation.

Curcumin mitigates the histopathological and molecular changes in sublingual glands in diabetic male rats

“…In this work, and in contrast to Huang et al 11 who did not detect obvious structural alterations in the sublingual glands of diabetic animals, the serous acinar cells, striated ducts and excretory ducts of the sublingual gland of diabetic rats depicted vacuolization. Our results are in line with the findings in earlier studies on the sublingual glands of diabetic animals.…”

Curcumin mitigates the histopathological and molecular changes in sublingual glands in diabetic male rats

“…In this work, and in contrast to Huang et al 11 who did not detect obvious structural alterations in the sublingual glands of diabetic animals, the serous acinar cells, striated ducts and excretory ducts of the sublingual gland of diabetic rats depicted vacuolization. Our results are in line with the findings in earlier studies on the sublingual glands of diabetic animals.…”

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function

“…In the current study, compared to the Control rats, the DM rats show decreased intestinal barrier function, as demonstrated by decreased gene and protein (colon) expression of Claudin-3. Our findings are consistent with the previous studies using HFD-induced prediabetic mice [ 22 ] and db/db diabetic mice [ 23 , 24 ]. Nascimento et al reported that the tight junction-mediated barrier in intestinal tissues, such as the duodenum, jejunum, ileum and colon epithelia, was significantly weakened in prediabetic mice [ 22 ].…”

Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

“…In keeping with our earlier statement, that barrier leak in diabetes is systemic and across many tissue types, diabetes-associated hyposalivation was shown to associate with altered TJ protein expression in parotid glands [ 23 ]. In addition, gestational diabetes in a rat model induced increased leak across the placental barrier along with decreased ZO-1 and occludin expression [ 238 ].…”

Curcumin mitigates the histopathological and molecular changes in sublingual glands in diabetic male rats

“…In this work, and in contrast to Huang et al 11 who did not detect obvious structural alterations in the sublingual glands of diabetic animals, the serous acinar cells, striated ducts and excretory ducts of the sublingual gland of diabetic rats depicted vacuolization. Our results are in line with the findings in earlier studies on the sublingual glands of diabetic animals.…”

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function

“…In the current study, compared to the Control rats, the DM rats show decreased intestinal barrier function, as demonstrated by decreased gene and protein (colon) expression of Claudin-3. Our findings are consistent with the previous studies using HFD-induced prediabetic mice [ 22 ] and db/db diabetic mice [ 23 , 24 ]. Nascimento et al reported that the tight junction-mediated barrier in intestinal tissues, such as the duodenum, jejunum, ileum and colon epithelia, was significantly weakened in prediabetic mice [ 22 ].…”

Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

“…In keeping with our earlier statement, that barrier leak in diabetes is systemic and across many tissue types, diabetes-associated hyposalivation was shown to associate with altered TJ protein expression in parotid glands [ 23 ]. In addition, gestational diabetes in a rat model induced increased leak across the placental barrier along with decreased ZO-1 and occludin expression [ 238 ].…”

Curcumin mitigates the histopathological and molecular changes in sublingual glands in diabetic male rats

“…In this work, and in contrast to Huang et al 11 who did not detect obvious structural alterations in the sublingual glands of diabetic animals, the serous acinar cells, striated ducts and excretory ducts of the sublingual gland of diabetic rats depicted vacuolization. Our results are in line with the findings in earlier studies on the sublingual glands of diabetic animals.…”

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function

“…In the current study, compared to the Control rats, the DM rats show decreased intestinal barrier function, as demonstrated by decreased gene and protein (colon) expression of Claudin-3. Our findings are consistent with the previous studies using HFD-induced prediabetic mice [ 22 ] and db/db diabetic mice [ 23 , 24 ]. Nascimento et al reported that the tight junction-mediated barrier in intestinal tissues, such as the duodenum, jejunum, ileum and colon epithelia, was significantly weakened in prediabetic mice [ 22 ].…”

Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

“…In keeping with our earlier statement, that barrier leak in diabetes is systemic and across many tissue types, diabetes-associated hyposalivation was shown to associate with altered TJ protein expression in parotid glands [ 23 ]. In addition, gestational diabetes in a rat model induced increased leak across the placental barrier along with decreased ZO-1 and occludin expression [ 238 ].…”