期刊
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
卷 15, 期 -, 页码 2583-2597出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DMSO.S375559
关键词
central nervous system; anorexic medications; sympathetic nervous system; chronic heart failure
资金
- Project of Key Medical Discipline of Pudong Hospital of Fudan University [Zdxk2020- 11]
- Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University [Zdzk2020-24]
- Integrative Medicine special fund of Shanghai Municipal Health Planning Committee [ZHYY- ZXYJHZX-2-201712]
- Special Department Fund of the Pudong New Area Health Planning Commission [PWZzk2017-03]
- Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai [PWR12014-06]
- Pudong New Area Clinical Plateau Discipline Project [PWYgy-2021-03]
- Natural Science Foundation of China [21675034]
- National Natural Science Foundation of China [81370932]
- Shanghai Natural Science Foundation [19ZR1447500]
- Education Funding in Wenzhou Medical University [JG2021197]
Diabetes and obesity are global issues associated with complications such as AMI and stroke. GLP-1RAs and SGLT-2is, new anti-diabetic medications, have beneficial effects on metabolism and the cardiovascular system, but their underlying mechanisms are poorly understood.
Diabetes and obesity are growing problems worldwide and are associated with a range of acute and chronic complications, including acute myocardial infarction (AMI) and stroke. Novel anti-diabetic medications designed to treat T2DM, such as glucagonlike peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is), exert beneficial effects on metabolism and the cardiovascular system. However, the underlying mechanisms are poorly understood. GLP-1RAs induce anorexic effects by inhibiting the central regulation of food intake to reduce body weight. Central/peripheral administration of GLP-1RAs inhibits food intake, accompanied by an increase in c-Fos expression in neurons within the paraventricular nucleus (PVN), amygdala, the nucleus of the solitary tract (NTS), area postrema (AP), lateral parabrachial nucleus (LPB) and arcuate nucleus (ARC), induced by the activation of GLP-1 receptors in the central nervous system (CNS). Therefore, GLP-1RAs need to pass through the blood-brain barrier to exert their pharmacological effects. In addition, studies revealed that SGLT-2is could reduce the risk of chronic heart failure in people with type 2 diabetes. SGLT-2 is extensively expressed throughout the CNS, and c-Fos expression was also observed within 2 hours of administration of SGLT-2is in mice. Recent clinical studies reported that SGLT-2is improved hypertension and atrial fibrillation by modulating the overstimulated renin-angiotensin-aldosterone system (RAAS) and suppressing the sympathetic nervous system (SNS) by directly/indirectly acting on the rostral ventrolateral medulla. Despite extensive research into the central mechanism of GLP-1RAs and SGLT-2is, the penetration of the blood-brain barrier (BBB) remains controversial. This review discusses the interaction between GLP-1RAs and SGLT-2is and the BBB to induce pharmacological effects via the CNS.
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