Sixteen family members carried the ABCC8 or KCNJ11 mutations; only two had hypoglycemia detected at birth and four others reported symptoms of hypoglycemia.
All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enroled and underwent a six-day continuous glucose monitoring (CGM) recording.
Non-islet cell hypoglycemia (NICH) is hypoglycemia due to the overproduction of insulin-like growth factor-2 (IGF-2) and its precursors which can activate the insulin receptor.
Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the β-cell ATP-sensitive K(+) channel (K(ATP) channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2).
Previous reports suggest a role for IGF2 over-expression in the pathogenesis of these tumours, implicated in triggering hypoglycaemia in some patients.
Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood.
We investigated the imprinting control and promoter usage for IGF2 expression to identify a mechanism for increased IGF-II production in non-islet-cell tumor hypoglycemia.
Glucose intolerance and diabetes are observed in the long-term follow-up of nonpancreatectomized patients with persistent hyperinsulinemic hypoglycemia of infancy due to mutations in the ABCC8 gene.
Defective expression of prohormone convertase 4 and enhanced expression of insulin-like growth factor II by pleural solitary fibrous tumor causing hypoglycemia.
These studies demonstrate in a variety of rodent models that systemic delivery of Kir6.2/SUR-1-selective KCOs enhance the glucose counterregulatory response to insulin-induced hypoglycemia.
We conclude that the heterozygous carriers of the SUR1 mutation had normal glucose metabolism and insulin secretion, indicating that carriers of recessive K(ATP) channel mutations are unlikely to be at an increased risk of hypoglycemia or other disturbances in glucose metabolism.
Mutations in the genes encoding Kir6.2 and SUR1 may result in familial persistent hyperinsulinemic hypoglycaemia of infancy, demonstrating their role in the regulation of insulin secretion.
These results suggest that a dysregulation of gene expression and imprinting of chromosome 11p15 region is associated with tumour growth and IGF-II overexpression in non-islet-cell tumour hypoglycaemia.
Hypoglycaemia associated with the production of insulin-like growth factor II and insulin-like growth factor binding protein 6 by a haemangiopericytoma.
Mutations in both the Kir6.2 and SUR1 genes are associated with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a disorder of pancreatic beta-cell function characterized by excess insulin secretion and hypoglycemia.