[Amelioration of latent skin lesions in streptozotocin-induced diabetic rats by insulin].
OBJECTIVE
To explore the latent skin lesions in streptozotocin-induced diabetic rats and the mechanism of insulin prevention.


METHODS
81 male Sprague-Dawley (SD) rats were randomized into control (C, n = 27) and STZ-induced diabetic groups (n = 54), and then the diabetic rats were randomized into 2 groups: Group A group (n = 27) that was treated with insulin enough to control the high concentration of blood glucose strictly, and Group B group (n = 27) in which insulin was given too nut not sufficient to control the high blood glucose. Twenty-seven normal rats were used as controls. Four, eight, and twelve weeks after STZ-induction, skin specimens from the back were collected to undergo hematoxylin-eosin staining and histological examination. The skin glucose content was measured by Beckman's autoanalyzer. The skin advanced glycation end products (AGEs) concentration was assessed by fluorescence spectrophotometry and immunohistochemistry. The ultrastructure changes of skin microvessel were observed by electron microscopy.


RESULTS
Twelve weeks after the establishment of the DM model the skin thickness of Group B was decreased, the features of multilayer epithelium structure disappeared in epidermis, and part of the collagen fibers in dermis became atrophic, swollen and degenerated, infiltration of inflammatory cells to different degrees was found, and subcutaneous fat showed progressive atrophy or disappeared. However, such changes were not detected in Group A. The skin glucose contents of Group B at different time points were all higher than those of Group A and Group (all P < 0.01) without a significant difference between Groups A and C. The fluorescence values of skin collagen extracts of Groups A and B were significantly higher than that of normal rats. The 8-week fluorescence value of skin collagen extracts of Groups B was 34 U/mg +/- 4 U/mg, significantly higher than that of Group A (29 U/mg +/- 3 U/mg, P < 0.05). The 12-week fluorescence value of skin collagen extracts of Groups B was 41 U/mg +/- 4 U/mg, significantly higher than that of Group A (32 U/mg +/- 4 U/mg, P < 0.05). The 8-week AGEs positive expression rate of Group B was 32% +/- 4%, significantly higher than that of Group A (25% +/- 5%, P < 0.05), and the 12-week AGEs positive expression rate of Group B was 39% +/- 5%, significantly higher than that of Group A (27% +/- 4%, P < 0.05). Degeneration of endothelial cells and thickening of basement membrane were more markedly in Group B than in Group A.


CONCLUSIONS
Accumulation of AGEs in skin and high concentration of glucose are important causes of diabetic skin complications. Insulin application at the early stage postpones the course of diabetic skin lesions with the possible mechanisms of lowering the high glucose, inhibiting AGEs synthesis, and blocking the action of AGEs.
Chen
Xiang-fang
XF
Department of Endocrinology, Chang zheng Hospital, Second Military Medical University, Shanghai 200003, China.
Lin
Wei-dong
WD
Lu
Shu-liang
SL
Zhang
Li-bin
LB
Zhang
Hui
H
Liu
Zhi-min
ZM
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000648:ultrastructure; D048909:Diabetes Complications / Q000378:metabolism / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000517:prevention & control*; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose