Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats

Kang, Won Yu; Jung, Woo Kwon; Park, Subin; Kim, Hyung Rae; Kim, Jung-Hyun

doi:10.1016/j.biopha.2021.111297

Cited by 9 publications

(8 citation statements)

References 41 publications

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“…Additionally, numerous existing studies have verified the antiglycation effect of many DPP-4 inhibitors [17][18][19][20]50]. Further, gemigliptin prevented a decline in salivary gland function through its antioxidant effect in diabetic rats [21]. We observed increased DPP4 activity, decreased GLP-1 levels, and elevated AGE accumulation in db/db mice.…”

Section: Discussionsupporting

confidence: 58%

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Effect of glucagon-like peptide 1 on salivary gland hypofunction in diabetic db/db mice

Kim,

Jung,

Kim

2023

J Biomed Transl Res

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Salivary gland dysfunction is a common complication of diabetes. Decreased saliva production and changes in saliva composition may cause oral diseases. Reactive oxygen species (ROS) generation in the salivary glands results in the loss of acinar cells and decreased saliva secretion. Glucagon-like peptide 1 (GLP-1) is the incretin hormone that regulates blood glucose level and can suppress ROS production and inflammation through its antioxidant effects. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that breaks down GLP-1. In this study, we evaluated the pathological role of DPP-4 and GLP-1 on salivary gland dysfunction in type 2 diabetic db/db mice. We observed reduced salivary secretion and histopathological alteration of salivary glands in the db/db mice. The increased DPP-4 and decreased GLP-1 levels in the salivary glands were also detected in the db/db mice. Furthermore, the db/db mice had increased apoptosis and oxidative injury in salivary glands. There was an accumulation of advanced glycation end products and mucus in the salivary glands of the db/db mice. In conclusion, these results showed the possible involvement of DPP-4 and GLP-1, leading to increased ROS-induced apoptosis in diabetes-related salivary gland dysfunction. DPP-4 and GLP-1 may be a pharmacological target for patients with diabetes-related salivary gland dysfunction.

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Section: Discussionsupporting

confidence: 58%

“…Recently, the DPP-4 inhibitor, alogliptin, was found to block the AGE-RAGE axis and reduce albuminuria in patients with type 2 diabetes [20]. Moreover, gemigliptin improved salivary gland function in streptozotocin-induced diabetic rats by exerting antioxidant and antiapoptotic effects [21].…”

Section: Introductionmentioning

confidence: 99%

Effect of glucagon-like peptide 1 on salivary gland hypofunction in diabetic db/db mice

Kim,

Jung,

Kim

2023

J Biomed Transl Res

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“…These results are thought to have resulted from the combination of female and male insulin resistance difference [34,35], the difference in pathogenesis for type 1 and 2 diabetes mellitus [36], and the usage, which requires a more detailed study to find the causes. However, in this study, it was possible to confirm the improvement of salivary gland hyposalivation by polydatin without the alleviation of hyperglycemia, which is considered to be a significant finding since there are therapeutic drugs that show a protective effect of diabetic complications without glycemic control [37].…”

Section: Discussionmentioning

confidence: 70%

Polydatin Alleviates Diabetes-Induced Hyposalivation through Anti-Glycation Activity in db/db Mouse

et al. 2021

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Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanuts, grapes, and red wine, and is known to have antiglycation, antioxidant, and anti-inflammatory effects. Diabetes mellitus is a very common disease, and diabetic complications are very common complications. The dry mouth symptom is one of the most common oral complaints in patients with diabetes mellitus. Diabetes mellitus is thought to promote hyposalivation. In this study, we aimed to investigate the improvement effect of polydatin on diabetes-induced hyposalivation in db/db mouse model of type 2 diabetes. We examined salivary flow rate, TUNEL assay, PAS staining, and immunohistochemical staining for AGEs, RAGE, HMGB1, 8-OHdG, and AQP5 to evaluate the efficacy of polydatin in the submandibular salivary gland. Diabetic db/db mice had a decreased salivary flow rate and salivary gland weight. The salivary gland of the vehicle-treated db/db mice showed an increased apoptotic cell injury. The AGEs were highly accumulated, and its receptor, RAGE expression was also enhanced. Expressions of HMGB1, an oxidative cell damage marker, and 8-OHdG, an oxidative DNA damage marker, increased greatly. However, polydatin ameliorated this hypofunction of the salivary gland and inhibited diabetes-related salivary cell injury. Furthermore, polydatin improved mucin accumulation, which is used as a damage marker for salivary gland acinar cells, and decreased expression of water channel AQP5 was improved by polydatin. In conclusion, polydatin has a potent protective effect on diabetes-related salivary gland hypofunction through its antioxidant and anti-glycation activities, and its AQP5 upregulation. This result suggests the possibility of the use of polydatin as a therapeutic drug to improve hyposalivation caused by diabetes.

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“…Our previous study reported that salivary acinal cells were histopathologically degenerated and damaged by apoptotic injury in the STZ-induced diabetic rats [15]. Thus, TUNEL staining was used to determine whether polydatin inhibits acinar cells die due to apoptosis.…”

Section: Polydatin Inhibits Apoptosis In the Salivary Glands Of Strep...mentioning

confidence: 99%

Preventive effect of polydatin on diabetes-related hypofunction of salivary gland in streptozotocin-induced diabetic rats

Kim¹,

Kim²

2021

J Biomed Transl Res

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Declined salivary gland function is commonly observed in patients with diabetes. Advanced glycation end products (AGEs) are believed to contribute to the pathogenesis of diabetes-induces hypofunction of the salivary glands. Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanut, grape, and red wines. Although polydatin is known to have anti-glycation, anti-oxidation, and anti-inflammation effects, its effect in the salivary gland is not known. In the present study, we evaluated the AGEs burden in the salivary gland in streptozotocin (STZ)-induced diabetic rats and the protective effect of polydatin on diabetes-related salivary hypofunction. Polydatin (50 and 100 mg/kg/day) was orally administered in the STZ-induced diabetic rats for 4 weeks. The results showed that the salivary flow rate of the STZ-induced diabetic rats was reduced compared with that in the normoglycemic control rats. The circulating AGEs in serum and secreted AGEs in saliva increased in the STZ-induced diabetic rats. The reactive oxygen specises (ROS) were highly generated in the salivary gland in these diabetic rats. The salivary gland from the diabetic rats showed increased acinar cell apoptosis compared to normoglycemic control mice. However, polydatin suppressed all of these diabetes-related salivary changes. Overall, polydatin could provide a beneficial option for diabetes-related salivary hypofunction.

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Gemigliptin suppresses salivary dysfunction in streptozotocin-induced diabetic rats

Cited by 9 publications

References 41 publications

Effect of glucagon-like peptide 1 on salivary gland hypofunction in diabetic db/db mice

Effect of glucagon-like peptide 1 on salivary gland hypofunction in diabetic db/db mice

Polydatin Alleviates Diabetes-Induced Hyposalivation through Anti-Glycation Activity in db/db Mouse

Preventive effect of polydatin on diabetes-related hypofunction of salivary gland in streptozotocin-induced diabetic rats

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