Meleleo Daniela, Cibelli Giuseppe, Valenzano Anna, Mastrodonato Maria, Mallamaci Rosanna
Department of Science of Agriculture, Food, Natural Resources and Engineering, University of Foggia, 71122 Foggia, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
Membranes (Basel). 2023 Nov 9;13(11):878. doi: 10.3390/membranes13110878.
The calcium ion (Ca) has been linked to type 2 diabetes mellitus (T2DM), although the role of Ca in this disorder is the subject of intense investigation. Serum Ca dyshomeostasis is associated with the development of insulin resistance, reduced insulin sensitivity, and impaired glucose tolerance. However, the molecular mechanisms involving Ca ions in pancreatic β-cell loss and subsequently in T2DM remain poorly understood. Implicated in the decline in β-cell functions are aggregates of human islet amyloid polypeptide (hIAPP), a small peptide secreted by β-cells that shows a strong tendency to self-aggregate into β-sheet-rich aggregates that evolve toward the formation of amyloid deposits and mature fibrils. The soluble oligomers of hIAPP can permeabilize the cell membrane by interacting with bilayer lipids. Our study aimed to evaluate the effect of Ca on the ability of the peptide to incorporate and form ion channels in zwitterionic planar lipid membranes (PLMs) composed of palmitoyl-oleoyl-phosphatidylcholine (POPC) and on the aggregation process of hIAPP molecules in solution. Our results may help to clarify the link between Ca ions, hIAPP peptide, and consequently the pathophysiology of T2DM.
钙离子（Ca）与2型糖尿病（T2DM）有关，尽管Ca在这种疾病中的作用是深入研究的主题。血清钙稳态失衡与胰岛素抵抗的发展、胰岛素敏感性降低和糖耐量受损有关。然而，涉及钙离子在胰腺β细胞丢失以及随后在T2DM中的分子机制仍知之甚少。β细胞功能下降与人类胰岛淀粉样多肽（hIAPP）的聚集有关，hIAPP是一种由β细胞分泌的小肽，具有很强的自我聚集倾向，形成富含β折叠的聚集体，进而形成淀粉样沉积物和成熟纤维。hIAPP的可溶性寡聚体可通过与双层脂质相互作用使细胞膜通透。我们的研究旨在评估Ca对该肽在由棕榈酰油酰磷脂酰胆碱（POPC）组成的两性离子平面脂质膜（PLM）中整合并形成离子通道的能力的影响，以及对溶液中hIAPP分子聚集过程的影响。我们的结果可能有助于阐明钙离子、hIAPP肽之间的联系，从而阐明T2DM的病理生理学。
