In contrast to 8 normal subjects and the remaining 10 first-degree relatives the secretion of glucagon by the 5 first degree relatives with abnormally low insulin release was not suppressed by induced hyperglycaemia.
These results suggest that mutant GCK may lead to chronic hyperglycaemia by raising the threshold of circulating glucose level which induces insulin secretion.
In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1.
A significant dissociation of IAPP and insulin secretion (associated with relatively greater upregulation of IAPP secretion) is observed in response to marked hyperglycemia, suggesting that IAPP and insulin expression are differentially regulated.
Glucose uptake into pancreatic beta cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia.
Islet cell antibodies (ICAs), thyrogastric antibodies, and HLA-DR antigens were determined in 204 patients with type II (non-insulin-dependent) diabetes controlled with diet and/or oral hypoglycemic agents (NIR) and in 108 age-matched patients who required insulin to control their hyperglycemia (IR). beta-Cell function measured as C-peptide response to glucagon was evaluated in relation to the presence of ICAs and HLA-DR antigens.
The greater the severity of the diabetes (greater fasting hyperglycemia) the greater the post-receptor defect, and in those patients with more significant fasting hyperglycemia the post-receptor defect is the predominant abnormality leading to the insulin resistant state.
The greater the severity of the diabetes (greater fasting hyperglycemia) the greater the post-receptor defect, and in those patients with more significant fasting hyperglycemia the post-receptor defect is the predominant abnormality leading to the insulin resistant state.
However, her endogenous immunoreactive insulin showed reduced biologic activity during a glucose-clamp study with hyperglycemia and a reduced ability to bind to the insulin receptor and stimulate glucose transport in vitro.
In conclusion, a study of endocrine aspects of a major glycosylation disorder revealed an age-dependent constellation, including hypergonadotropic hypogonadism with deficient FSH rather than LH action; transient hyperthyrotropinemia; inconsistent hyperprolactinemia; hyperglycemia-induced growth hormone release; deficiencies of hormone-binding glycoproteins and possibly decreased insulin sensitivity, thus pointing to the importance of glycoprotein glycosylation for pediatric endocrinology.
In conclusion, a study of endocrine aspects of a major glycosylation disorder revealed an age-dependent constellation, including hypergonadotropic hypogonadism with deficient FSH rather than LH action; transient hyperthyrotropinemia; inconsistent hyperprolactinemia; hyperglycemia-induced growth hormone release; deficiencies of hormone-binding glycoproteins and possibly decreased insulin sensitivity, thus pointing to the importance of glycoprotein glycosylation for pediatric endocrinology.
Her metabolic and hormonal features were marked hyperglycemia (11-33 mmol/L) and hyperinsulinemia (1000-2000 pmol/L); normal free fatty acids and lactate; low IGF-I; glycerol, alanine, and pyruvate below the normal range; and elevated beta-hydroxybutyrate.
These characteristics of the dose-response relationships between glucose and insulin secretion result in a more severe degree of hyperglycemia than observed in subjects with glucokinase mutations, and these subjects more frequently need insulin treatment.
We investigated two potential mechanisms that might be relevant for the abnormal function of the insulin receptor in NIDDM, i.e. changes in the expression of the receptor isoforms and the effect of hyperglycaemia on insulin receptor tyrosine kinase activity.
Together, the data suggest that the regulatory serine or threonine phosphorylation site(s) involved in the inhibitory effect of hyperglycemia are neither located in the C-terminus nor in the juxtamembrane region of the insulin receptor beta subunit.
The epithelial adaptations to hyperglycemia of uncontrolled diabetes are accomplished by increasing the glucose transport surface area and the number of the efflux glucose transporter GLUT2 located in the basolateral membrane.