Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Treatment
2.2. Zoometry
2.3. Oral Glucose Tolerance Test, Insulin Response, and Insulin Resistance Analyses
2.4. Biochemical Assays
2.5. Tissue for Biochemical, Immunoassay, and Histological Tests
2.6. Biochemical Assays
2.7. Redox Balance Assays
2.8. Immunoassays
2.9. Histological Assays
2.10. Statistical Analysis
3. Results
3.1. Hyperinsulinemia-Euglycemia Model
3.2. Insulin Resistance Model
3.3. Glargine Administration Impairs Hepatic Insulin Metabolic Signaling
3.4. Effect of Glargine Administration on Serum Lipid Profile
3.5. Effect of Insulin Glargine Administration on Hepatic Redox Balance and MAPK Response
3.6. Insulin Glargine Administration on the Hepatic Inflammation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | 15 Days | 30 Days | 45 Days | 60 Days | ||||
---|---|---|---|---|---|---|---|---|
Control | Insulin | Control | Insulin | Control | Insulin | Control | Insulin | |
Weight (g) | 167 ± 5.83 | 162.8 ± 2.4 | 192.6 ± 6.6 | 205.8 ± 8.3 | 250 ± 10 | 251 ± 6 | 287 ± 15 | 291.4 ± 16 |
Size (cm) | 15.6 ± 0.19 | 15.3 ± 0.20 | 17.4 ± 0.3 | 18.1 ± 0.4 | 19.4 ± 0.24 | 19.4 ± 0.5 | 21.2 ± 4.2 | 20.3 ± 1 |
BMI | 0.69 ± 0.01 | 0.68 ± 0.02 | 0.64 ± 0.01 | 0.62 ± 0.02 | 0.67 ± 0.04 | 0.67 ± 0.02 | 0.63 ± 0.1 | 0.68 ±0.4 * |
% Fat | 34.6 ± 0.21 | 34.2 ± 0.4 | 32.6 ± 0.4 | 31.7 ± 0.51 | 31.9 ± 0.6 | 31.9 ± 0.5 | 24.3 ± 6 | 32.6 ± 2 * |
Fasting glucose (mg/dL) | 98.5 ± 5.1 | 116 ± 6.5 * | 93 ± 3.9 | 117 ± 4.1 * | 97 ± 5.1 | 131.6 ± 4.7 * | 93.6 ± 6.8 | 112 ± 5 * |
Glucose 30′ (mg/dL) | 154.5 ± 4.3 | 164.6 ± 3.9 | 114.4 ± 5.1 | 143.5 ± 4.9 | 113 ± 4.3 | 159 ± 3.9 * | 119.5 ± 6.5 | 167.5 ± 4.5 * |
Glucose 60′ (mg/dL) | 165.7 ± 5.5 | 177.2 ± 6.8 | 89.6 ± 4 | 148 ± 2.1 * | 133.3 ± 4.6 | 164.5 ± 4.1 * | 117.7 ± 3.3 | 141 ± 10 * |
Glucose 90′ (mg/dL) | 179.3 ± 4.2 | 200.5 ± 5.1 * | 97 ± 5 | 126.5 ± 4.4 * | 108.3 ± 2.3 | 162.4 ± 5.2 * | 115 ± 8 | 188.5 ± 5.5 * |
Glucose AUC | 13,775 | 15,020 | 8,970 | 12,398 * | 10,470 | 14,118 * | 10,245 | 14,065 * |
Insulin fasting (µUI/mL) | 43.3 ± 3.4 | 51.0 ± 4.5 | 12.5 ± 1.6 | 16.5 ± 2.2 | 12.2 ± 1.2 | 14.1 ± 2.4 | 9.7 ± 1 | 12.2 ± 0.6 * |
Insulin 30′ (µUI/mL) | 52.1 ± 4.1 | 56.3 ± 2.5 | 13.1 ± 2.5 | 15.6 ± 2.1 | 19 ± 2.2 | 20.2 ± 1.9 | 11.7 ± 1.7 | 23.8 ± 0.7 * |
Insulin 60′ (µUI/mL) | 64.8 ± 3.8 | 67.5 ± 4.0 | 12.1 ± 2.3 | 20.1 ± 3.4* | 17.1 ± 1.5 | 28.1 ± 2.3 * | 11.5 ± 1 | 33.8 ± 1.3 * |
Insulin 90′ (µUI/mL) | 69.7 ± 5.1 | 72.5 ± 3.4 | 9.2 ± 1.5 | 22.5 ± 1.1 * | 13.1 ± 2.3 | 18.5 ± 2.4 * | 10.3 ± 0.6 | 23.8 ± 0.9 * |
Insulin AUC | 5205 | 5291 | 1112 | 1635 * | 1469 | 1694 * | 1000 | 1762 * |
HOMA-IR | 1.0 ± 0.04 | 1.6 ± 0.07 | 0.45 ± 0.01 | 0.73 ± 0.04 * | 0.49 ± 0.03 | 0.68 ± 0.08 * | 0.36 ± 0.02 | 0.58 ± 0.01 * |
QUICKY | 0.28 ± 01 | 0.26 ± 0.06 | 0.40 ± 0.03 | 0.31 ± 0.001 * | 0.38 ± 0.04 | 0.30 ± 0.01 * | 0.36 ± 0.07 | 0.32 ± 0.01 * |
Matsuda-DeFronzo | 1.6 ± 0.06 | 1.35 ± 0.06 | 1.3 ± 0.02 | 0.90 ± 0.08 * | 6.63 ± 0.03 | 4.04 ± 0.19 * | 7.61 ± 1.1 | 4.26 ± 0.1 * |
HIS | 4.25 ± 0.26 | 2.71 ± 0.32 * | 16.6 ± 0.84 | 10.21 ± 0.6 * | 15.3 ± 0.9 | 11.2 ± 1 * | 16.5 ± 3.1 | 10.1 ± 0.4 * |
LIRI | 1.1 ± 0.08 | 1.3 ± 0.08 | 0.28 ± 0.13 | 0.48 ± 0.05 | 0.24 ± 0.2 | 0.39 ± 0.01* | 0.2 ± 0.02 | 0.41 ± 0.02 * |
Parameter | 15 Days | 30 Days | 45 Days | 60 Days | ||||
---|---|---|---|---|---|---|---|---|
Control | Insulin | Control | Insulin | Control | Insulin | Control | Insulin | |
Triglycerides | 77 ± 2.37 | 51.2 ± 1.59 * | 95.3 ± 2.2 | 68.2 ± 3.5 * | 100 ± 4.3 | 125 ± 6.7 * | 97 ± 4.8 | 123 ± 4.9 * |
VLDL | 15.4 ± 0.47 | 10.2 ± 0.32 * | 19 ± 0.4 | 13.6 ± 0.71 * | 21.5 ± 0.9 | 25 ± 1.3 * | 19.4 ± 0.9 | 24 ± 1.1 * |
ApoB | 10.5± 1.70 | 9.8± 1.16 | 9.7 ± 1 | 8.3 ± 0.8 | 11.6 ± 1 | 10.6 ± 1.5 | 10.9 ± 0.96 | 13.1 ±0.8 * |
HDL | 42.8 ± 1.1 | 32.8 ± 2.8 * | 65 ± 2.2 | 55 ± 1.5 * | 70.2 ± 2 | 63.7 ± 2.8 * | 50.6 ± 1.2 | 43 ± 2 * |
FFA | 7.8 ± 0.33 | 10.4 ± 0.49 * | 9.1 ± 0.08 | 11.6 ± 0.4 * | 7.1 ± 0.5 | 7.7 ± 0.2 * | 9.9 ± 0.2 | 11.8 ± 0.24 * |
15 Days | 30 Days | 45 Days | 60 Days | |||||
---|---|---|---|---|---|---|---|---|
Control | Insulin | Control | Insulin | Control | Insulin | Control | Insulin | |
Total Glutathione (μM/mg of protein) | 19.1 ± 2.2 | 15.4 ± 2.1 | 18.9 ± 2.5 | 15.0 ± 1.4 | 18.5 ± 2.4 | 16.7 ± 1.9 | 18.9 ± 1.2 | 20.3 ± 1.4 |
GSH (μM/mg of protein) | 13.0 ± 1.3 | 2.5 ± 0.7 * | 12.6 ± 1.8 | 2.7 ± 1.5 * | 13.3 ± 1.7 | 5.5 ± 1.4 * | 12.9 ± 1.6 | 11 ± 1.3 |
GSSG (μM/mg of protein) | 6.2 ± 0.8 | 14.8 ± 1.0 * | 6.3 ± 0.6 | 12.7 ± 1.5 * | 6.8 ± 0.9 | 11.6 ± 1.1 * | 6.5 ± 1.1 | 10.3 ± 1.7 * |
2GSH/GSSG | 4.2 ± 1.0 | 0.3 ± 0.09 * | 4.0 ± 0.5 | 0.4 ± 0.02 * | 4.1 ± 0.4 | 0.6 ± 0.9 * | 4.2 ± 0.8 | 2.2 ± 0.7 * |
GPx (U min−1/mg of protein) | 2.6 ± 0.1 | 3.1 ± 0.1 | 2.3 ± 0.1 | 2.9 ± 0.2 | 3.1 ± 0.4 | 3.2 ± 0.8 | 2.9 ± 0.2 | 3.3 ± 0.4 |
GR (U min−1/mg of protein) | 1016.2 ± 77 | 1555.9 ± 160 * | 1147.7 ± 170 | 1759.6 ± 218 * | 1051 ± 134 | 1654 ± 121 * | 1152 ± 181 | 1893 ± 162 * |
GT (U min−1/mg of protein) | 839.9 ± 81 | 988.1 ± 123 | 658.2 ± 92 | 958.7 ± 126 | 758.2 ± 140 | 896.4 ± 132 | 792 ± 164 | 784.4 ± 170 |
SOD (U min−1/mg of protein) | 8.0 ± 0.4 | 7.1 ± 0.5 | 7.6 ± 0.9 | 7.2 ± 0.5 | 7.7 ± 0.3 | 7.5 ± 0.4 | 7.9 ± 0.9 | 7.3 ± 1.4 |
CAT (U min−1/mg of protein) | 19.9 ± 2.4 | 18.0 ± 2.3 | 19.5 ± 1.8 | 18.4 ± 2.4 | 19.1 ± 1.9 | 18.5 ± 1.3 | 20.1 ± 1.4 | 19.7 ± 2.3 |
MT (μg/mg of protein) | 1.84 ± 0.2 | 2.4 ± 0.3* | 1.3 ± 0.3 | 2.5 ± 0.5 * | 1.9 ± 0.3 | 2.7 ± 0.7* | 1.7 ± 0.4 | 2.6 ± 0.2 * |
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Sarmiento-Ortega, V.E.; Moroni-González, D.; Diaz, A.; García-González, M.Á.; Brambila, E.; Treviño, S. Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration. Metabolites 2023, 13, 572. https://doi.org/10.3390/metabo13040572
Sarmiento-Ortega VE, Moroni-González D, Diaz A, García-González MÁ, Brambila E, Treviño S. Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration. Metabolites. 2023; 13(4):572. https://doi.org/10.3390/metabo13040572
Chicago/Turabian StyleSarmiento-Ortega, Victor Enrique, Diana Moroni-González, Alfonso Diaz, Miguel Ángel García-González, Eduardo Brambila, and Samuel Treviño. 2023. "Hepatic Insulin Resistance Model in the Male Wistar Rat Using Exogenous Insulin Glargine Administration" Metabolites 13, no. 4: 572. https://doi.org/10.3390/metabo13040572