The role of beta-cell dysfunction in the cardiometabolic syndrome.
The regulation of blood glucose levels involves a finely tuned relationship between insulin sensitivity, hepatic glucose output, and production of insulin. The cardiometabolic syndrome includes in its definition criteria a disturbance of normal glucose tolerance and implies development of both insulin resistance and beta-cell dysfunction. There is now abundant evidence pointing toward a central role of dysregulation of the beta-cell function and mass in the development of impaired glucose tolerance. Mechanisms implicated in beta-cell dysfunction include genetic abnormalities, prenatal and early postnatal insults, and environmental events along with obesity, dyslipidemia-lipotoxicity, glucotoxicity, oxidative stress, chronic low-grade inflammation, amyloid deposition, and activation of the local renin-angiotensin system. Novel therapeutic characteristics of known medications such as metformin, thiazolidinediones, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and novel medications such as exendin-4 promise encouraging possibilities to battle against the cardiometabolic syndrome and the future development of cardiovascular disease.
Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Diabetes, and Cardiovascular Disease Research Center, University of Missouri School of Medicine, Columbia, MO, USA.
Guido
G
Lastra
Camila Margarita
CM
Manrique
Melvin R
MR
Hayden
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007333:Insulin Resistance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D024821:Metabolic Syndrome / Q000276:immunology* / Q000473:pathology; D018384:Oxidative Stress / Q000276:immunology*; D012307:Risk Factors