Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling
Abstract
:1. Molecular Mechanism for Pancreatic β-Cell Dysfunction
1.1. MafA and PDX-1 Play a Crucial Role in Pancreatic β-Cells
1.2. Incretin Signaling Plays an Important Role in Pancreatic β-Cells
1.3. Incretin Receptor Expression in β-Cells Is Downregulated under Diabetic Conditions: Incretin-Based Agents Exert More Protective Effects on β-Cells at an Early Stage of Diabetes rather than an Advanced Stage
1.4. Impaired Insulin Signaling in Endothelial Cells Leads to Pancreatic β-Cell Dysfunction
2. Incretin Signaling and Atherosclerosis
2.1. Incretin Signaling Plays an Important Role in Arteries
2.2. Incretin Receptor Expression in Arteries Is Downregulated under Diabetic Conditions
2.3. Large-Scale Clinical Trials Regarding the Protective Role of Incretin-Based Agents against Atherosclerosis in Subjects with Type 2 Diabetes Mellitus: SPAED-A and SPIKE Trials
2.4. Large-Scale Clinical Trials Regarding the Protective Role of Incretin-Based Agents against Cardiovascular Events in Subjects with Type 2 Diabetes Mellitus: LEADER, SUSTAIN-6, REWIND, PIONEER 6 Trials
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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SPEAD-A | SPIKE | LEADER | SUSTAIN-6 | REWIND | PIONEER 6 | |
---|---|---|---|---|---|---|
Medication | Alogliptin vs. control | Sitagliptin vs. control | Liraglutide vs. control | Semaglutide vs. control | Dulaglutide vs. control | Oral semaglutide vs. control |
Treatment Period | 2 years | 2 years | 3.8 years | 2 years | 5.4 years | 1.3 years |
Primary Outcome | Carotid IMT | Carotid IMT | Cardiovascular outcome | Cardiovascular outcome | Cardiovascular outcome | Cardiovascular outcome |
Results | Mean IMT p = 0.022 | Mean IMT p = 0.005 | Composite outcome HR: 0.87 (CI: 0.78–0.97) | Composite outcome HR: 0.74 (CI: 0.58–0.95) | Composite outcome HR: 0.88 (CI: 0.79–0.99) | Composite outcome HR: 0.79 (CI: 0.57–1.11) |
Right max IMT p = 0.025 | Left max IMT p = 0.021 | Cardiovascular death HR: 0.78 (CI: 0.66–0.93) | Nonfatal MI HR: 0.74 (CI: 0.51–1.08) | All-cause death HR: 0.90 (0.80–1.01) | Cardiovascular death HR: 0.49 (CI: 0.27–0.92) | |
Left max IMT p = 0.013 | All-cause death HR: 0.85 (CI: 0.74–0.97) | Nonfatal stroke HR: 0.61 (CI: 0.38–0.99) | All-cause death HR: 0.51 (CI: 0.31–0.84) |
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Kaneto, H.; Obata, A.; Kimura, T.; Shimoda, M.; Sanada, J.; Fushimi, Y.; Katakami, N.; Matsuoka, T.; Kaku, K. Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling. Int. J. Mol. Sci. 2020, 21, 9444. https://doi.org/10.3390/ijms21249444
Kaneto H, Obata A, Kimura T, Shimoda M, Sanada J, Fushimi Y, Katakami N, Matsuoka T, Kaku K. Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling. International Journal of Molecular Sciences. 2020; 21(24):9444. https://doi.org/10.3390/ijms21249444
Chicago/Turabian StyleKaneto, Hideaki, Atsushi Obata, Tomohiko Kimura, Masashi Shimoda, Junpei Sanada, Yoshiro Fushimi, Naoto Katakami, Takaaki Matsuoka, and Kohei Kaku. 2020. "Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling" International Journal of Molecular Sciences 21, no. 24: 9444. https://doi.org/10.3390/ijms21249444