Delayed wound healing in diabetes is caused by neuropathy, vascular changes, and impaired cellular response to the injury. Macrophages are crucial in normal wound healing, and impaired functions of these cells have been shown in diabetes. beta-1,3-D-glucans stimulate macrophage function. This open-label study was performed to see if aminated beta-1,3-D-glucan (AG) stimulates wound healing in diabetes. Four groups (1-4) of diabetic db/db mice and one nondiabetic control group, db/+(5) were studied: group 1 (n=11): topical AG; group 2 (n=10): topical AG and subcutaneous insulin; group 3 (n=14): topical placebo and subcutaneous insulin; group 4 (n=10): diabetic control (placebo); group 5 (n=12): normal control (placebo). At the end of the experiments fasting blood glucose and A1C were (mean +/- SE) as follows: Group 1: 30.5 +/- 1.9 mmol/L and 11.3 +/- 0.6%; group 2: 12.0 +/- 1.7 mmol/L and 8.0 +/- 0.6%; group 3: 15.4 +/- 2.4 mmol/L and 7.4 +/- 0.3%; group 4: 32.6 +/- 2.6 mmol/L and 12.3 +/- 0.6%; group 5: 7.2 +/- 0.4 mmol/L and 3.9 +/- 0.04%, respectively. The closed wound area was the same in group 1 (AG alone) and group 2 (AG plus insulin) after 17 days, 57.3 +/- 4.7 vs. 50.1 +/- 4.9% (p=0.7). The results of these two groups were superior to group 3 (insulin treatment alone, 32.0 +/- 4.3%, p<0.001) and diabetic controls (38.2 +/- 5.1%, p=0.001). The macrophage-stimulant AG improves wound healing in db/db mice.
Inflammatory responses are common in diabetes and are operative in angiopathy, neuropathy, and wound healing. There are indications of incomplete macrophage activation in diabetes and reduced expression of growth factors. We have previously found that up to 15 topical applications of the macrophage-stimulant, aminated β-1,3-D-glucan (AG), improved wound healing in db/db mice. The present open-label study was undertaken to examine dose-dependent effects of AG over 40 days in db/db mice. AG was given as a single dose (group 1), one dose every 10th day (group 2), five initial doses on consecutive days (group 3), and ≥15 doses (group 4). Controls were db/db mice receiving platelet-derived growth factor + insulin-like growth factor-1 (group 5), topical placebo (NaCl 9 mg/mL) and insulin (group 6), placebo (group 7), and a nondiabetic group receiving placebo (group 8). Seven to 14 animals were allocated to each group. Percentage wound closure 17 days after surgery in groups 1 and 2 were (mean ± standard error of the mean) 25.5 ± 5.3 and 32.2 ± 6.3, respectively. Corresponding closure in groups 3, 4, and 5 was 55.7 ± 5.0, 57.3 ± 5.0, and 55.6 ± 4.8, respectively (p < 0.05 vs. groups 1 and 2). Groups 6, 7, and 8 closed 32.0 ± 4.5, 38.2 ± 5.3, and 98.5 ± 0.4%, respectively. Significant association between the number of AG-dosages and wound closure indicates dose-related effects in db/db mice.
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