epidermal-growth-factor and Hypoglycemia

We investigated the physiological role of epidermal growth factor (EGF) in fetal growth in mice in which midgestational sialoadenectomy induced maternal EGF deficiency. Sialoadenectomy decreased the fetal weight significantly, indicating that maternal EGF deficiency caused intrauterine growth retardation. The weight of the fetal liver in the sialoadenectomized mice was reduced in proportion to the decrease in body weight (82.7+/-10.2 vs. 70.9+/-10.9 mg), whereas the brain weight was not reduced. Sialoadenectomy significantly decreased the glucose concentration in fetal plasma (86.0+/-13.0 vs. 63.0+/-11.8 mg/dl) without affecting the maternal plasma level of glucose. Transplacental transfer of 3H-2-deoxyglucose was significantly decreased by sialoadenectomy (5.17+/-1.25 vs. 2.94+/-1.02%), but transfer of 14C-aminoisobutyric acid was not affected. Northern blot analysis and in situ hybridization of glucose transporter isoform GLUT1 and GLUT3 messenger RNAs (mRNAs) in placenta revealed that sialoadenectomy significantly reduced the expression of GLUT3 mRNA without affecting GLUT1 mRNA levels. Administration of anti-EGF antiserum enhanced the effects of EGF deficiency, which were almost completely corrected by EGF supplementation. These results indicate that EGF plays an important role in fetal growth by regulating the transplacental supply of glucose via GLUT3 expression in the placenta.

Topics: Aminoisobutyric Acids; Animals; Blood Glucose; Deoxyglucose; Epidermal Growth Factor; Female; Fetal Blood; Fetal Growth Retardation; Fetus; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 3; Hypoglycemia; Mice; Mice, Inbred C3H; Monosaccharide Transport Proteins; Nerve Tissue Proteins; Placenta; Pregnancy; Pregnancy, Animal; Tissue Distribution

Many growth factors are implicated in proliferative diabetic retinopathy (PDR). It was decided to test the hypothesis that no one factor is predominant but that a regular profile of levels of different growth factors might be operating, and that the profile might differ according to whether or not insulin therapy was part of the patient's glycaemic management. The levels of several growth factors in vitrectomy samples were therefore determined from diabetic patients with tractional, non-haemorrhagic sequelae of PDR and these levels were correlated with (a) each other (growth factor profile), (b) neovascular activity, and (c) the method of glycaemic management (insulin treated (IT) or non-insulin treated (NIT)).. 72 samples of vitreous were obtained from either diabetic patients with PDR (n = 51) or non-diabetic (control) patients (n = 21). Levels of bFGF, IGF-I, EGF, and insulin were determined by radioimmunoassay; levels of TGF-beta 2 by ELISA; and levels of IGF-I binding protein by western ligand blotting. The data were analysed using appropriate statistics.. There was no regular growth factor profile. bFGF levels were significantly greater in vitreous from NIT patients compared with IT patients and controls. The highest levels of bFGF were found in NIT patients with actively vascularised membranes. TGF-beta 2 levels were significantly greater in vitreous from IT patients compared with NIT patients and controls The highest levels of TGF-beta 2 were found in IT patients with actively vascularised membranes. IGF-I levels were significantly greater in diabetics (irrespective of insulin treatment) than non-diabetics and the highest levels of IGF-I were found in IT patients with actively vascularised membranes. A 34 kDa IGFBP was the predominant IGFBP identified in vitreous and was found to be elevated in diabetics patients.. In PDR there is a correlation between intravitreal growth factor levels and both disease state (whether active or fibrotic) and method of glycaemic management.

Topics: Analysis of Variance; Case-Control Studies; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Fibroblast Growth Factor 2; Growth Substances; Humans; Hypoglycemia; Insulin; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor II; Middle Aged; Neovascularization, Pathologic; Radioimmunoassay; Transforming Growth Factor beta; Vitreous Body

A substance immunochemically cross-reactive with insulin (SICRI) appears in melanoma B16 growing in diabetic and nondiabetic C57BL/6 mice. Progression of tumor size is paralleled by the increase of SICRI levels in the serum of both diabetic and nondiabetic animals; this increase correlates with a decreased concentration of circulating glucose and an elevated concentration of growth hormone in blood. Melanoma B16 grown under serum-free culture conditions secretes SICRI into the medium. Affinity-purified SICRI stimulates glucose uptake by rat epididymal adipocytes and competes with radiolabeled insulin for binding to these cells. Low concentrations of SICRI enhance growth of cultured melanoma B16 cells, whereas high concentrations of this substance have inhibitory growth effects on these cells. Porcine insulin, human insulin-like growth factors I and II, human growth hormone, platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor have negligible influence on growth of melanoma B16.

Topics: Adipose Tissue; Animals; Diabetes Mellitus, Experimental; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Hormone; Homeostasis; Hypoglycemia; Insulin; Melanoma; Mice; Platelet-Derived Growth Factor; Somatomedins