Endothelial Insulin Resistance Exacerbates Experimental Periodontitis

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.