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Endothelial Insulin Resistance Exacerbates Experimental Periodontitis.

T Zeze¹, T Shinjo¹, K Sato¹

¹Section of Periodontology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.

Journal of Dental Research

|July 14, 2023

Summary

This summary is machine-generated.

Endothelial insulin resistance in the gingiva promotes periodontitis by increasing VCAM1 expression and leukocyte adhesion. This occurs via reduced PI3K/Akt/FoxO1 pathway activation, worsening alveolar bone loss.

Keywords:

VCAM-1 alveolar bone loss cell adhesion molecules forkhead box protein O1 periodontal diseases type 2 diabetes

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Area of Science:

Oral Biology
Endocrinology
Immunology

Background:

Periodontitis severity is higher in individuals with diabetes.
Molecular mechanisms of diabetes-related periodontitis are unclear.
Insulin resistance in gingival tissues may contribute to diabetic complications.

Purpose of the Study:

Investigate endothelial insulin resistance in the gingiva's role in periodontitis pathogenesis.
Elucidate the molecular mechanisms linking endothelial insulin resistance to periodontitis.

Main Methods:

Examined insulin's effect on VCAM1 expression in endothelial cells (ECs) via the PI3K/Akt pathway.
Utilized vascular endothelial cell-specific insulin receptor knockout (VEIRKO) mice.
Analyzed the role of FoxO1 in insulin-mediated regulation of VCAM1 and leukocyte adhesion.

Main Results:

Insulin treatment downregulated VCAM1 expression in ECs via PI3K/Akt, reducing leukocyte adhesion.
Hyperglycemia-induced insulin resistance in ECs diminished insulin's effect on VCAM1.
VEIRKO mice showed increased periodontitis and bone loss, with upregulated VCAM1, TNFα, MCP-1, and RANKL.
Insulin-mediated FoxO1 activation was suppressed in VEIRKO mice and hyperglycemia-treated ECs.
Mutated FoxO1 attenuated insulin's regulation of VCAM1 and leukocyte adhesion.

Conclusions:

Endothelial insulin resistance contributes to periodontitis progression.
Dysregulated VCAM1 expression and leukocyte adhesion result from impaired PI3K/Akt/FoxO1 signaling.
Targeting endothelial insulin resistance may offer therapeutic strategies for periodontitis in diabetic patients.