SLC16A1-associated hyperinsulinism

Etiology

The SLC16A1 gene encodes the monocarboxylate transporter1 (MCT1) that mediates the movement of lactate and pyruvate across cell membranes Import and export of these substrates by tissues such as erythrocytes, muscle, intestine, and kidney are ascribed largely to the action of a proton-coupled MCT. SLC16A1 is not usually transcribed in beta cells.

SLC16A1 gene, which encodes monocarboxylate transporter 1 (MCT1), and leads to hypoglycemia in case of activating mutations exercise-induced hyperinsulinism (EIHI).

 promoter-activating mutations in SLC16A1 (monocarboxylate transporter 1) in exercise-induced hyperinsulinism (EIHI or SLC16A1-associated hyperinsulinism)

• exercise-induced hyperinsulinism (EIHI) is a dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load.
• promoter-activating mutations in SLC16A1 increases expression of SLC16A1 in beta cells
• oromoter-activating mutations in SLC16A1 permits pyruvate uptake and pyruvate-stimulated insulin release despite ensuing hypoglycemia
• SLC16A1 is not usually transcribed in beta cells.

This disease mechanism is based on the failure of cell-specific transcriptional silencing of a gene that is highly expressed in other tissues.

See also

 beta -cell regulation

References

 Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, Schuit F, Quintens R, Sipila I, Mayatepek E, Meissner T, Halestrap AP, Rutter GA, Kere J. Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. Am J Hum Genet. 2007 Sep;81(3):467-74. PMID: 17701893