scholarly journals Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Shu Kikuta ◽  
Akihito Kuboki ◽  
Tatsuya Yamasoba

Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

2012 ◽  
Vol 90 (3) ◽  
pp. 371-378 ◽  
Author(s):  
Menakshi Bhat Dusane ◽  
Bimba N. Joshi

The present study investigates the antidiabetogenic effects of Murraya koenigii (L.) Spr. and Ocimum tenuflorum  L. on streptozotocin-induced diabetic Swiss mice. Treatment with extracts of M. koenigii (chloroform; MKC) and O. tenuflorum (aqueous; OTA) resulted in proper glucose utilization with an increase in liver glucose-6-phosphate dehydrogenase enzyme activity, and normal glycogenesis in hepatic and muscle tissues. Pancreatic and intestinal glucosidase inhibitory activity observed with MKC and OTA treatment indicated beneficial effects in reducing postprandial hyperglycemia with concomitant improvement in glucose metabolism. The glucosidase inhibition was prolonged, even after discontinuation of MKC and OTA treatment. Normalization of plasma insulin and C-peptide levels was observed in diabetic mice, indicating endogenous insulin secretion after treatment. The histochemical and immunohistochemical analysis of pancreatic islets suggests the role of MKC and OTA in pancreatic β-cell protection and the functional pancreatic islets that produce insulin. The study demonstrates the significance of MKC and OTA in glucosidase inhibition and islet protection in the murine diabetic model. These findings suggest the potential of the extracts in adjuvant therapy for the treatment of diabetes and the possible development of potential neutraceuticals.


2015 ◽  
Vol 36 (6) ◽  
pp. 2307-2316 ◽  
Author(s):  
Xiaohui Xu ◽  
Tao Liang ◽  
Xing Lin ◽  
Qingwei Wen ◽  
Xingmei Liang ◽  
...  

Background: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM) in ancient China, has been reported to have anti-diabetic efficacy. Aims: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR) on the regulation of the Toll-like receptor 4 (TLR4)-Nuclear-factor kappa B (NF-κB) pathway in B) pathway in streptozotocin (STZ)-induced diabetic mice. Methods: the mice were injected with STZ (120 mg/kg body weight) via a tail vein. After 72 h, the mice with FBG = 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) for 14 days. Results: As a result the serum fasting blood glucose (FBG), interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. Conclusion: These findings suggest that the modulation of the IL-6 and TNF-a inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.


1987 ◽  
Vol 65 (9) ◽  
pp. 1982-1987 ◽  
Author(s):  
Walter Zingg ◽  
Aron M. Rappaport ◽  
Bernard S. Leibel

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.


2018 ◽  
Vol 19 (12) ◽  
pp. 4016 ◽  
Author(s):  
Valéria da Silva ◽  
Aurigena de Araújo ◽  
Daline Araújo ◽  
Maíra Lima ◽  
Roseane Vasconcelos ◽  
...  

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.


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