Cell-Specific Effects of Insulin in a Murine Model of Restenosis Under Insulin-Sensitive and Insulin-Resistant Conditions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Model and Animal Experiments
2.2. Diet Treatment
2.3. Generation of Cell-Specific IR-Deficient Mice
2.4. Insulin Pellet Implantation and Surgical Procedure
2.5. Blood Glucose Assessment and Blood Sample Collection
2.6. Insulin Tolerance Test
2.7. Fixed Vessel Collection and Morphological Analysis
2.8. Immunofluorescence
2.9. Statistical Analysis
3. Results
3.1. Generation of Cell-Specific IR-Deficient Mice
3.2. Metabolic Parameters
3.3. Cell-Specific Effects of Insulin on Neointimal Growth under Insulin-Sensitive Conditions
3.3.1. Insulin’s Anti-Restenotic Effect Is Abolished in LFD-Fed EC-Specific IR-Deficient Mice
3.3.2. Insulin’s Anti-Restenotic Effect Is Abolished in LFD-Fed SMC-Specific IR-Deficient Mice
3.3.3. Insulin Treatment Reduces Neointimal Growth in LFD-Fed IRW/W-Cre(+) Control Mice
3.4. HFSD Induces Insulin Resistance in Control and Cell-Specific IR-Deficient Mice
3.5. Cell-Specific Effects of Insulin on Neointimal Growth under Insulin-Resistant Conditions
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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LFD, Vehicle | LFD, Insulin | HFSD, Vehicle | HFSD, Insulin | |||||
---|---|---|---|---|---|---|---|---|
IRf/f Cre (−) | IRf/f Cre (+) | IRf/f Cre (−) | IRf/f Cre (+) | IRf/f Cre (−) | IRf/f Cre (+) | IRf/f Cre (−) | IRf/f Cre (+) | |
Body Weight (g) | 25.7 ± 0.7 | 27.4 ± 0.7 | 26.1 ± 0.5 | 25.5 ± 0.6 | 31.4 ± 0.7 * | 33 ± 1.2 * | 30.2 ± 0.6 * | 29.3 ± 0.9 * |
Fasted Plasma Glucose (mM) | 11.1 ± 0.6 | 10.0 ± 0.6 | 9.9 ± 0.5 | 9.9 ± 0.6 | 14.6 ± 0.6 * | 14 ± 0.8 * | 13.8 ± 0.3 * | 13 ± 0.4 * |
Fed Plasma Glucose (mM) | 10.5 ± 0.3 | 10.1 ± 0.2 | 10.4 ± 0.2 | 9.5 ± 0.3 | 12.9 ± 0.2 * | 12.3 ± 0.4 * | 12.5 ± 0.4 * | 12.7 ± 0.7 * |
Fed Insulin (pM) | 200 ± 85 | 200 ± 58 | 540 ± 120 $ | 469 ± 88 $ | 131± 23 | 88 ± 12 | 474± 110 $ | 507 ± 148$ |
Fed IGF-1 (pg/mL) | 506 ± 81 | 404 ± 90 | 472 ± 45 | 402 ± 36 | 776 ± 64 * | 623 ± 79 * | 604 ± 60 * | 570 ± 46 * |
Fed VEGF (pg/mL) | 21.7 ± 1.5 | 24.9 ± 1.43 | 23.4 ± 1.44 | 25.7 ± 1.86 | 25.5 ± 1.39 | 23.2 ± 1.42 | 27.7 ± 2.10 | 26.7 ± 1.70 |
Fed Triglycerides (mM) | 1.4 ± 0.1 | 1.6 ± 0.1 | 1.1 ± 0.1 $ | 0.8 ± 0.2 $ | 1.7 ± 0.1 * | 1.5 ± 0.2 * | 1.3 ± 0.1 *$ | 1.3 ± 0.2 *$ |
Fed Free Fatty Acids (mM) | 0.63 ± 0.04 | 0.58 ± 0.04 | 0.52 ± 0.03 $ | 0.49 ± 0.04 $ | 0.75 ± 0.05 * | 0.66 ± 0.04 * | 0.59 ± 0.02 *$ | 0.58 ± 0.02 *$ |
Total cholesterol (mM) | 1.4 ± 0.18 | 1.3 ± 0.17 | 1.4 ± 0.31 | 1.4 ± 0.43 | 2.7 ± 0.31 * | 2.3 ± 0.38 * | 3.1 ± 1.0 * | 2.3 ± 0.44 * |
LFD, Vehicle | LFD, Insulin | HFSD, Vehicle | HFSD, Insulin | |||||
---|---|---|---|---|---|---|---|---|
IRf/fCre (−) | IRf/f Cre (+) | IRf/f Cre (−) | IRf/f Cre (+) | IRf/f Cre (−) | IRf/f Cre (+) | IRf/f Cre (−) | IRf/f Cre (+) | |
Body Weight (g) | 25.7 ± 0.7 | 26 ± 0.5 | 26.1 ± 0.5 | 25.8 ± 0.5 | 31.4 ± 0.7 * | 29.4 ± 0.4 * | 30.2 ± 0.6 * | 31 ± 0.4 * |
Fasted Plasma Glucose (mM) | 11.1 ± 0.6 | 11.2 ± 0.3 | 9.9 ± 0.5 | 10.3 ± 0.7 | 14.6 ± 0.6 * | 14.6 ± 0.7 * | 13.8 ± 0.3 * | 14.5 ± 0.9 * |
Fed Plasma Glucose (mM) | 10.5 ± 0.3 | 10.4 ± 0.3 | 10.4 ± 0.2 | 9.9 ± 0.6 | 12.8 ± 0.2 * | 12.5 ± 0.4 * | 12.8 ± 0.4 * | 12.2 ± 0.8 * |
Fed Insulin (pM) | 200 ± 85 | 111 ± 26 | 540 ± 120 $ | 439 ± 103 $ | 131 ± 23 | 87 ± 12 | 474 ± 110 $ | 344 ± 55 $ |
Fed IGF-1 (pg/mL) | 506 ± 81 | 562 ± 33 | 472 ± 45 | 376 ± 53 | 776 ± 64 * | 650 ± 14 * | 604 ± 60 * | 560 ± 44 * |
Fed VEGF (pg/mL) | 21.7 ± 1.5 | 25.5 ± 1.39 | 23.4 ± 1.44 | 27.7 ± 2.10 | 25.5 ± 1.39 | 24.2 ± 1.44 | 27.7 ± 2.10 | 27.2 ± 1.09 |
Fed Triglycerides (mM) | 1.4 ± 0.1 | 1.5 ± 0.2 | 1.1 ± 0.1 $ | 0.9 ± 0.1 $ | 1.7 ± 0.1 * | 1.5 ± 0.1 * | 1.3 ± 0.1 *$ | 1.5 ± 0.1 *$ |
Fed Free Fatty Acids (mM) | 0.63 ± 0.04 | 0.54 ± 0.04 | 0.52 ± 0.03 $ | 0.40 ± 0.04 $ | 0.75 ± 0.05 * | 0.69 ± 0.02 * | 0.59 ± 0.02 *$ | 0.63 ± 0.02 *$ |
Total cholesterol (mM) | 1.4 ± 0.18 | 1.7 ± 0.21 | 1.4 ± 0.31 | 1.1 ± 0.27 | 2.7 ± 0.31 * | 2.0 ± 0.16 * | 3.1 ± 1.0 * | 2.1 ± 0.19 * |
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Gonzalez Medina, M.; Liu, Z.; Wang, J.; Zhang, C.; Cash, S.B.; Cummins, C.L.; Giacca, A. Cell-Specific Effects of Insulin in a Murine Model of Restenosis Under Insulin-Sensitive and Insulin-Resistant Conditions. Cells 2024, 13, 1387. https://doi.org/10.3390/cells13161387
Gonzalez Medina M, Liu Z, Wang J, Zhang C, Cash SB, Cummins CL, Giacca A. Cell-Specific Effects of Insulin in a Murine Model of Restenosis Under Insulin-Sensitive and Insulin-Resistant Conditions. Cells. 2024; 13(16):1387. https://doi.org/10.3390/cells13161387
Chicago/Turabian StyleGonzalez Medina, Marel, Zhiwei Liu, Johny Wang, Cindy Zhang, Sarah B. Cash, Carolyn L. Cummins, and Adria Giacca. 2024. "Cell-Specific Effects of Insulin in a Murine Model of Restenosis Under Insulin-Sensitive and Insulin-Resistant Conditions" Cells 13, no. 16: 1387. https://doi.org/10.3390/cells13161387