Mueller Jonathan Wolf, Thomas Patricia, Dalgaard Louise Torp, da Silva Xavier Gabriela
Department of Metabolism and Systems Science, University of Birmingham, Birmingham, U.K.
Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Essays Biochem. 2024 Dec 4;68(4):509-522. doi: 10.1042/EBC20240034.
Diabetes Type 1 and Type 2 are widely occurring diseases. In spite of a vast amount of biomedical literature about diabetic processes in general, links to certain biological processes are only becoming evident these days. One such area of biology is the sulfation of small molecules, such as steroid hormones or metabolites from the gastrointestinal tract, as well as larger biomolecules, such as proteins and proteoglycans. Thus, modulating the physicochemical propensities of the different sulfate acceptors, resulting in enhanced solubility, expedited circulatory transit, or enhanced macromolecular interaction. This review lists evidence for the involvement of sulfation pathways in the maintenance of functional pancreatic beta-cell mass and the implications for diabetes, grouped into various classes of sulfated biomolecule. Complex heparan sulfates might play a role in the development and maintenance of beta-cells. The sulfolipids sulfatide and sulfo-cholesterol might contribute to beta-cell health. In beta-cells, there are only very few proteins with confirmed sulfation on some tyrosine residues, with the IRS4 molecule being one of them. Sulfated steroid hormones, such as estradiol-sulfate and vitamin-D-sulfate, may facilitate downstream steroid signaling in beta-cells, following de-sulfation. Indoxyl sulfate is a metabolite from the intestine, that causes kidney damage, contributing to diabetic kidney disease. Finally, from a technological perspective, there is heparan sulfate, heparin, and chondroitin sulfate, that all might be involved in next-generation beta-cell transplantation. Sulfation pathways may play a role in pancreatic beta-cells through multiple mechanisms. A more coherent understanding of sulfation pathways in diabetes will facilitate discussion and guide future research.
1型和2型糖尿病是广泛发生的疾病。尽管关于糖尿病一般过程的生物医学文献数量众多，但与某些生物过程的联系直到最近才变得明显。生物学的一个这样的领域是小分子的硫酸化，例如类固醇激素或胃肠道代谢物，以及较大的生物分子，如蛋白质和蛋白聚糖。因此，调节不同硫酸受体的物理化学倾向，导致溶解度增加、循环运输加快或大分子相互作用增强。这篇综述列出了硫酸化途径参与功能性胰腺β细胞群维持的证据以及对糖尿病的影响，并分为不同类别的硫酸化生物分子。复杂的硫酸乙酰肝素可能在β细胞的发育和维持中起作用。硫脂硫酸脑苷脂和硫酸胆固醇可能有助于β细胞健康。在β细胞中，只有极少数蛋白质在某些酪氨酸残基上有确定的硫酸化，IRS4分子就是其中之一。硫酸化的类固醇激素，如硫酸雌二醇和硫酸维生素D，在去硫酸化后可能促进β细胞中的下游类固醇信号传导。硫酸吲哚酚是一种肠道代谢物，会导致肾脏损伤，是糖尿病肾病的一个原因。最后，从技术角度来看，硫酸乙酰肝素、肝素和硫酸软骨素都可能参与下一代β细胞移植。硫酸化途径可能通过多种机制在胰腺β细胞中发挥作用。对糖尿病中硫酸化途径更连贯的理解将有助于讨论并指导未来的研究。
