Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives

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Genetic variants causing loss of sucrase-isomaltase (SI) function result in malabsorption of sucrose and starch components and the condition congenital sucrase-isomaltase deficiency (CSID). The identified genetic variants causing CSID are very rare in all surveyed populations around the globe, except the Arctic-specific c.273_274delAG loss-of-function (LoF) variant, which is common in the Greenlandic Inuit and other Arctic populations. In these populations, it is, therefore, possible to study people with loss of SI function in an unbiased way to elucidate the physiological function of SI, and investigate both short-term and long-term health effects of reduced small intestinal digestion of sucrose and starch. Importantly, a recent study of the LoF variant in Greenlanders reported that adult homozygous carriers have a markedly healthier metabolic profile. These findings indicate that SI inhibition could potentially improve metabolic health also in individuals not carrying the LoF variant, which is of great interest considering the massive number of individuals with obesity and type 2 diabetes worldwide. Therefore, the objectives of this review, are 1) to describe the biological role of SI, 2) to describe the metabolic impact of the Arctic SI LoF variant, 3) to reflect on potential mechanisms linking reduced SI function to metabolic health, and 4) to discuss what knowledge is necessary to properly evaluate whether SI inhibition is a potential therapeutic target for improving cardiometabolic health.

TidsskriftApplication of Clinical Genetics
Sider (fra-til)31-39
Antal sider9
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center, based at the University of Copenhagen, Denmark, and partially funded by an unconditional donation from the Novo Nordisk Foundation ( (Grant number NNF18CC0034900).

Funding Information:
NKS received funding from The Greenland Institute of Natural Resources (postdoctoral grant number 80.045) and The Greenlandic Research Council; held shares in Novo Nordisk AS, but sold in 2022. IM was supported by a Danish National Research Foundation Award (DNRF 143). MEJ received grants from the Independent Research Fund Denmark (grant number 1030-00363B); research grants from Boehringer Ingelheim, Novo Nordisk AS, and Sanofi Aventis, and holds shares in Novo Nordisk AS. TH was supported by a grant from Novo Nordisk Foundation (Grant number 0064142). The authors report no other conflicts of interest in this work

Publisher Copyright:
© 2023 Senftleber et al.

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