The anti-apoptotic effect of IGF1 on Schwann cells inflicted by hyperglycemia is mediated at least by neuritin, a novel neurotrophic factor, through PI3K and Bcl-2.
Hyperglycemia at the post-starvation period induced the expression of insulin-like growth factor-1, hypoxia-induced factor-1α and Nanog, as well as the phosphorylation of Stat3.
In addition, due to their lack of specificity, IGF-1R tyrosine kinase inhibitors are associated with hyperglycemia as a result of interference with signaling through the classical metabolic INSR-B isoform; this may preclude their use at clinically effective doses.
Growth hormone insensitivity syndrome (GHIS) is caused by a defective growth hormone receptor (GHR) and is associated with insulin-like growth factor-I (IGF-I) deficiency, severely short stature and, from adolescence, fasting hyperglycemia and obesity.
IGF-1 secretion and IGF receptor phosphorylation by autocrine IGF-1 occur equally in euglycemic or hyperglycemic conditions, suggesting that reduced RUNX2 activity in response to hyperglycemia is not because of altered IGF-1/IGF receptor activation.
Finally, due to a partial prevention of beta-cell death against onset of diabetes and/or the insulin-like effects of IGF-I overexpression, MT-IGF mice (which overexpress the IGF-I gene under the metallothionein I promoter) were significantly resistant to streptozotocin-induced diabetes, with diminished hyperglycemia and prevention of weight loss and death.
Effects of hyperglycemia on the differential expression of insulin and insulin-like growth factor-I receptors in human normal peritoneal and adhesion fibroblasts.
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.
The chronic sc administration of insulin-like growth factor I (IGF-I) improved the patient's hyperglycemia and corrected certain metabolic abnormalities over a 9-month period, even though the binding of 125I-labeled IGF-I to her cultured fibroblasts was decreased by 40% relative to that to cells from healthy controls.