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A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Crosstalk Between Oxidative Stress, Protein Glycation, and Extracellular Matrix Remodeling in the Skin of Rats with
Natalia Dorf1, Edyta Gołaś2,3, Cezary Pawlukianiec2
1Independent Laboratory of Cosmetology, Medical University of Bialystok, 3 Akademicka Street, 15-267 Bialystok, Poland.
Abstract:
The exact mechanisms of skin involvement in type 1 diabetes (DM1) remain poorly understood. This study aimed to evaluate the relationship between antioxidants, oxidative stress, protein glycation, and glycoxidation, as well as matrix metalloproteinase (MMP) activity, in the skin of rats with DM1, while investigating whether insulin administration improves skin homeostasis. Male Wistar rats were assigned to three groups: control, diabetes, and diabetes treated with insulin. Significantly higher expression of GSH (gluthatione) and GSH-Px (glutathione peroxidase), elevated levels of AGE (Advanced Glycation End products), DT (dityrosine), KN (kynurenine), NFKN (N-formylkynurenine) and ONOO- (peroxynitrite), as well as increased activity of GLU (β-D-glucuronidase), NADPH oxidase (NOX) and MMP-1, -2, -3, -7, -9, -11 and -13 were observed in the skin of rats with DM1. Insulin treatment normalizes the skin's antioxidant barrier and eliminates oxidative stress. It also reduces the intensity of protein glycation and glycoxidation, though not to the levels observed in the control group. Summarizing, in diabetic skin there is a complex interaction between the thiol antioxidant barrier, oxidative damage, protein glycation and glycoxidation as well as MMP expression. Insulin restores physiological balance in skin cells; however, glycation and ECM remodeling are still more pronounced than in healthy skin.
Insights
Type 1 diabetes (DM1) significantly alters skin by increasing oxidative stress and matrix metalloproteinase (MMP) activity. Insulin therapy restores skin homeostasis, reducing these effects but not fully reversing glycation and remodeling.
Area of Science:
- Biochemistry
- Dermatology
- Endocrinology
Background:
- The skin manifestations of type 1 diabetes (DM1) are not fully understood.
- Oxidative stress, protein glycation, and matrix metalloproteinase (MMP) activity are implicated in diabetic complications.
Purpose of the Study:
- To investigate the interplay between antioxidants, oxidative stress, protein glycation/glycoxidation, and MMP activity in the skin of DM1 rats.
- To determine if insulin administration can restore skin homeostasis in DM1.
Main Methods:
- Male Wistar rats were divided into control, diabetes, and insulin-treated diabetes groups.
- Skin samples were analyzed for glutathione (GSH), glutathione peroxidase (GSH-Px), advanced glycation end products (AGEs), dityrosine, kynurenine, N-formylkynurenine, peroxynitrite, β-D-glucuronidase, NADPH oxidase, and MMP activity.
- Skin homeostasis markers were assessed post-insulin treatment.
Main Results:
- Diabetic rats exhibited elevated GSH, GSH-Px, AGEs, dityrosine, kynurenine, N-formylkynurenine, peroxynitrite, β-D-glucuronidase, NADPH oxidase, and MMPs (-1, -2, -3, -7, -9, -11, -13) compared to controls.
- Insulin treatment normalized the antioxidant barrier and eliminated oxidative stress.
- Protein glycation and glycoxidation decreased with insulin but remained higher than in controls, indicating persistent extracellular matrix remodeling.
Conclusions:
- Diabetic skin displays a complex imbalance involving the antioxidant system, oxidative damage, protein glycation, and MMP expression.
- Insulin therapy effectively restores physiological balance in diabetic skin by mitigating oxidative stress and normalizing the antioxidant barrier.
- Despite insulin's benefits, persistent glycation and extracellular matrix remodeling highlight the long-term challenges in diabetic skin health.
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