Because the serum level of IGF binding protein-3 was low, whereas the serum insulin level and other endocrinological examinations were normal, we speculate that the mechanism of the hypoglycemia was associated with the tumor-produced IGF2.
We postulated that the pathogenesis of her hypoglycemia involved production of IGF-II by her neuroblastoma, leading to GH suppression and an abnormally elevated ratio of IGF to IGF binding protein.
An insulin-like growth factor II-producing histiocytoma associated with hypoglycemia: analysis of the peptide, its gene expression, and glucose transporter isoforms.
In 25 of 28 patients with this type of hypoglycemia we found 1.5-8-fold elevated serum levels of immunoreactive big (15-25 kD), but decreased levels of normal IGF II.
There is now convincing evidence that some tumors secrete sufficient IGF-II to have systemic endocrine effects as recognized as nonislet cell tumor hypoglycemia.
We found that 57% +/- 4.6% of the IGF-II in sera from patients with hypoglycemia was present as big IGF-II compared with 22% +/- 3% in patients with euglycemia with hepatomas (not significantly different from that in normal controls).
We suggest that the primary event in tumor-induced hypoglycemia is overproduction of IGF-II by the tumor, which gives rise to hypoglycemia by a dual mechanism: increased glucose utilization mediated by the insulin-like actions of IGF-II and inhibition of GH secretion.
These data suggest that nonislet cell tumors associated with hypoglycemia produce large amounts of IGF-II mRNA and that this IGF-II mRNA appears to be the product of an IGF-II gene, which is apparently normal in the region encoding mature IGF-II peptide.
In HNF4A-MODY and HNF1A-MODY patients, normal or even increased insulin sensitivity together with glucose-independent mechanism of action of the first-line therapy - sulphonylurea derivatives - often leads to hypoglycemia, even at the much lower dose used in type 2 diabetes.
Neonatal hypoglycemia is generally observed in MODY 1 infants, but it is possible to hypothesize that some HNF-1α mutations could lead to a functionally impaired protein that might dysregulate HNF-4α expression determining hypoglycemia.
Of note, 40% of people with HNF1A-MODY and medical treatment were receiving insulin alone and thus were not being treated in line with up-to-date International Society for Pediatric and Adolescent Diabetes/International Diabetes Federation guidelines, despite insulin treatment being associated with worse metabolic control and the risk of hypoglycaemia.
The observation of fetal macrosomia and hypoglycemia in childhood is suggestive of a biphasic impact of the HNF1A mutation on beta-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.
The observation of fetal macrosomia and hypoglycemia in childhood is indicative of a biphasic impact of the HNF1A mutation on p-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.
Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity.
Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity.
These data indicate that mutations of HNF-1alpha in MODY3 do not result in a decreased glucagon secretion or alterations of glucose production during hypoglycemia.