In celebration of a century with insulin - Update of insulin gene mutations in diabetes
| Autor: | Julie Støy, Elisa De Franco, Soo-Young Park, Graeme I. Bell, Andrew T. Hattersley, Honggang Ye |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Inheritance Patterns Review Gene mutation SRP signal recognition particle History 21st Century Pathophysiology ER endoplasmic reticulum TNDM transient neonatal diabetes UPR unfolded protein response Monogenic diabetes Insulin-Secreting Cells Diabetes mellitus PNDM permanent neonatal diabetes Genetic variation Diabetes Mellitus medicine Genetics Humans Insulin Age of Onset Child Internal medicine Molecular Biology Gene IQR interquartile range Insulin biosynthesis Insulin Gene business.industry SU sulfonylurea Infant Newborn Neonatal diabetes Infant NDM neonatal diabetes mellitus Cell Biology OHA oral hypoglycaemic agent Endoplasmic Reticulum Stress medicine.disease RC31-1245 Insulin gene Child Preschool Mutation Unfolded protein response MODY maturity-onset diabetes of the young business |
| Zdroj: | Støy, J, De Franco, E, Ye, H, Park, S-Y, Bell, G I & Hattersley, A T 2021, ' In celebration of a century with insulin-Update of insulin gene mutations in diabetes ', Molecular Metabolism, vol. 52, 101280 . https://doi.org/10.1016/j.molmet.2021.101280 Molecular Metabolism Molecular Metabolism, Vol 52, Iss, Pp 101280-(2021) |
| Popis: | Background While insulin has been central to the pathophysiology and treatment of patients with diabetes for the last 100 years, it has only been since 2007 that genetic variation in the INS gene has been recognised as a major cause of monogenic diabetes. Both dominant and recessive mutations in the INS gene are now recognised as important causes of neonatal diabetes and offer important insights into both the structure and function of insulin. It is also recognised that in rare cases, mutations in the INS gene can be found in patients with diabetes diagnosed outside the first year of life. Scope of Review This review examines the genetics and clinical features of monogenic diabetes resulting from INS gene mutations from the first description in 2007 and includes information from 389 patients from 292 families diagnosed in Exeter with INS gene mutations. We discuss the implications for diagnosing and treating this subtype of monogenic diabetes. Major Conclusions The dominant mutations in the INS gene typically affect the secondary structure of the insulin protein, usually by disrupting the 3 disulfide bonds in mature insulin. The resulting misfolded protein results in ER stress and beta-cell destruction. In contrast, recessive INS gene mutations typically result in no functional protein being produced due to reduced insulin biosynthesis or loss-of-function mutations in the insulin protein. There are clinical differences between the two genetic aetiologies, between the specific mutations, and within patients with identical mutations. Highlights • Dominant and recessive mutations in the insulin (INS) gene are important causes of neonatal diabetes. • Associated phenotypes are variable in terms of age at diabetes onset, birth weight and treatment requirements. • Dominant mutations affect the secondary structure of the insulin protein, resulting in beta-cell ER stress and destruction. • Recessive mutations result in reduced insulin biosynthesis or loss-of-function mutations of the insulin protein. • The studies of these forms of diabetes offer important insights into the structure, biosynthesis and secretion of insulin. |
| Databáze: | OpenAIRE |
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