Sleep fragmentation delays wound healing in a mouse model of type 2 diabetes

This study tested the hypothesis that sleep fragmentation (SF) delays wound healing in obese B6.BKS(D)-Leprdb/J (db/db) mice with impaired leptin signaling and type 2 diabetes compared with wild-type C57BL/6J (B6) mice.

Adult male mice (n = 34) were anesthetized and bilateral full-thickness excisional wounds were created on the back of each mouse. Half of the db/db and B6 mice were housed in SF cages equipped with a bar that moved across the cage floor every 2 min, 12 hr/day for 23 days. The other half of each group of mice was housed in the same room and did not experience SF. The dependent measures were number of days required to achieve wound closure, mRNA expression of four inflammatory mediators, blood glucose, insulin, and corticosterone.

SF in the db/db mice caused a significant delay in wound healing relative to db/db mice with no SF. Days to achieve 50 per cent wound healing were 13.3 ± 0.4 with SF compared with 10.3 ± 0.7 without SF. All B6 mice achieved 50 per cent wound healing within 6 days and complete healing after 16 days. SF caused a significant increase in wound levels of TNF-α mRNA only in the db/db mice and an increase in corticosterone only in the B6 mice.

The delayed wound healing in obese, diabetic mice caused by SF is homologous to delayed wound healing in some patients with type 2 diabetes. The results support the interpretation that altered leptinergic signaling and inflammatory proteins contribute to delayed wound healing.