Cholesterol plays an essential role in determining cell membrane physico-chemical characteristics and functions. A proper membrane structure is critical in pancreatic β-cells for glucose-mediated insulin secretion, and alterations in cellular cholesterol content may negatively affect this process, leading to β-cell dysfunction. The low density lipoprotein receptor (LDL-R) appears to play a relevant role in ß-cell dysfunction due to cholesterol accumulation. This observation raised the question of whether hypocholesterolemic drugs which increase LDL-R expression might bear diabetogenic properties, thus increasing the risk of new-onset diabetes or worsen glycaemic parameters in diabetic patients. Being at higher cardiovascular risk, diabetic patients are usually treated with hypolipidemic drugs to correct the atherogenic dyslipidemia characteristic of this pathological condition. Statin therapy has been associated with an increased incidence of new-onset diabetes (NOD), being the diabetogenic effect depending on the type and dose of statin. However, it is worth noting that the benefits on cardiovascular mortality largely exceed the increased risk associated with the development of diabetes. Although genetic variants associated with lower levels of LDL-C are also associated with an increased NOD risk, clinical trials with lipid-lowering drugs other than statins, namely ezetimibe or monoclonal antibodies against PCSK9, did not observe an increase of developing diabetes. In summary, molecular evidence clearly points to a key role for cholesterol homeostasis in pancreatic β-cell function which, in humans, is negatively affected by statins. Available data exclude that this could be the case for other hypocholesterolemic approaches, but long-term studies are warranted to explore this critical aspect.
Cholesterol metabolism, pancreatic β-cell function and diabetes / C. Perego, L. Da Dalt, A. Pirillo, A. Galli, A.L. Catapano, G.D. Norata. - In: BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE. - ISSN 0925-4439. - 1865:9(2019 Sep 01), pp. 2149-2156.
|Titolo:||Cholesterol metabolism, pancreatic β-cell function and diabetes|
PEREGO, CARLA (Primo)
DA DALT, LORENZO (Secondo)
CATAPANO, ALBERICO LUIGI (Penultimo) (Corresponding)
NORATA, GIUSEPPE DANILO (Ultimo)
|Parole Chiave:||Cholesterol; Diabetes; Hypocholesterolemic drugs; Insulin; β-cell|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore BIO/09 - Fisiologia
|Progetto:||Immunometabolic effects of apolipoprotein E: focus on the modulation of cholesterol metabolism in antigen presenting cells|
Proprotein convertase subtilisin/kexin type 9 (PCSK9): a link between lipotoxicity, mitochondrial dysfunction, and frailty-associated heart failure
Targeting epigenetic REPROGRamming of innate immune cells in Atherosclerosis Management and other chronic inflammatory diseases
|Data di pubblicazione:||1-set-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bbadis.2019.04.012|
|Appare nelle tipologie:||01 - Articolo su periodico|