Growth Assessment in Clinical Practice: Whose Growth Curve?

Differences in growth curves can influence the diagnosis of under- and overnutrition, and the interpretation of adequate growth following nutrition intervention. This effect is notable when comparing the World Health Organization (WHO) 2006 Growth Standard and the Centers for Disease Control and Prevention (CDC) 2000 Growth Reference for infants and children to 59 months of age. Important differences relate to conceptual approaches for generating growth standards to describe what population growth should be, compared to a reference of what growth is. WHO included only term infants exclusively or predominantly breast-fed beyond 4 months, and data for infants and children indicative of excess adiposity and growth failure were removed. Thus, fewer children are diagnosed with poor weight gain, and more with excess adiposity, using the WHO Growth Standard than when using the CDC Growth Reference. Adequate growth is based on proportional height and weight gains that track along growth curve trajectories. Use of the WHO curves should assist in prevention of inappropriate intervention or overfeeding in young children.     

Insulin Enhances Epidermal Growth Factor- and Transforming Growth Factor- α-Stimulated Growth in Primary Cultures of Guinea Pig Gastric Mucous Epithelial Cells

Rutten MJ, Harmon P, Campbell DR. Insulin enhances epidermal growth factor-and transforming growth factor-α-stimulated growth in primary cultures of guinea pig gastric mucous epithelial cells. Scand J Gastroenterol 1991, 26, 965–973

The effect of insulin on epidermal growth factor (EGF)- and transforming growth factor-α (TGFα)-induced cell proliferation was examined in primary cultures of gastric surface mucous epithelial cells by using changes in cell counts and DNA as indices of cell growth. With 1.0% fetal bovine serum and Dulbecco's modified Eagle medium (low-serum DMEM) there was no effect of bovine insulin (0.1–10.0 μg/ml) on cell growth. Higher doses of insulin (20.0 μg/ml) in low-serum DMEM were able to stimulate growth of these cells compared with controls. In low-serum DMEM with no insulin the lowest effective dose of EGF or TGFα for stimulating cell growth was 10 nM and 5 nM, respectively. In low-serum DMEM containing 2.5 μg/ml insulin there was a dose-dependent increase in cell growth with EGF and TFGα at concentrations of 0.5–10.0 nM. The addition of insulin alone at 2.5 μg/ml, EGF alone at 2 nM, or TGFα alone at 2 nM in serum-free DMEM media had no effect on gastric surface mucous cell DNA. In serum-free DMEM media with 2.5 μg/ml insulin, the addition of 2 nM EGF or 2 nM TGFα- caused an increase in both cell counts and DNA of 1.80- and 3.50-fold, respectively. The present study demonstrates that insulin, at concentrations that are not mitogenic, will enhance the proliferative effects of EGF and TGFα on the growth of primary cultures of guinea pig gastric surface mucous epithelial cells.     

Growth Hormone and Insulin-like Growth Factor 1: New Endocrine Therapies in Cardiology?

The hormones growth hormone (GH) and insulin-like growth factor 1 (IGF-1) play a dominant role in whole body growth and metabolism. This is reflected in the use of human GH (hGH) in GH-deficient children to stimulate growth and in GH-deficient adults to reduce visceral fat mass. Recent data suggest that hGH may improve cardiac function in patients with heart failure, so there is current interest in methods to raise GH-IGF levels, including the testing of agents that release GH from the pituitary, administering IGF-1, and most recently, long-acting formulations of hGH. It is hoped that this ongoing integration of cardiology and endocrinology will uncover the pathophysiology of some cardiovascular diseases and yield new treatments based on the hormones of the GH axis. (Trends Cardiovasc Med 1997;7:264-268). ? 1997, Elsevier Science Inc.     

Growth factor signalling in the regulation of α-cell fate

Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic α-cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring β-cells are emerging as central modulator(s) of α-cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the α-cell-specific insulin receptor knockout (αIRKO) mouse manifests hypersecretion of glucagon in the postprandial stage and exhibits defective secretion in fasting-induced hypoglycaemia, together mimicking the α-cell defects observed in type 2 diabetes. Interestingly, αIRKO mice display a progressive increase in β-cell mass and a concomitant decrease in α-cells. Lineage trace analyses reveal that the new β-cells originate, in part, from the insulin receptor-deficient α-cells indicating a critical role for α-cell insulin signalling in determining β-cell origin. Our studies also reveal that glucagon-like peptide-1 (GLP-1) treatment of αIRKO mice suppresses glucagon secretion despite absence of functional insulin receptors precluding a role for insulin in GLP-1 action on α-cells in this model. These findings highlight the significance of insulin signalling in the regulation of α-cell biology.     

Transforming Growth Factor-α Precursors in Human Colon Carcinoma Cells

Among the proteins of the epidermal growth factor family, transforming growth factor- (TGF-) may be an especially reliable indicator of metastasis or prognosis in human colorectal carcinomas. Moreover, anomalous forms of TGF- have been detected in several tissues of cancer origin, suggesting a role of these forms in the development of the disease. This study was designed to identify the presence of TGF- precursors in different colon cancer cell lines by mean of immunocytochemistry and western blotting techniques. Pro-TGF- was detected in all cell lines tested. Staining for pro-TGF- was observed in cytoplasm. Monoclonal antibody to TGF- detected two bands of 20 and 21 kDa. Polyclonal antibody to pro-TGF- revealed five bands ranging from 15 to 24 kDa. All these proteins were also detected in nonmalignant cells expressing a transfected rat pro-TGF- gene. In conclusions, transformation in these human colon carcinoma cells is not due to the presence of anomalous forms of TGF- precursors.     

Growth hormone: a new therapy for heart failure?

There is now little doubt that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) play a role in cardiac development and in cardiovascular physiology in adult life. Congenital lack of GH is associated with defective cardiac growth, ventricular wall thinning, and impaired systolic function. These abnormalities limit exercise capacity and contribute to the poor quality of life in patients with GH deficiency. In addition, studies with in vitro muscle preparations have shown that IGF-1 affects myocardial contractility by a direct mechanism. These findings suggested that GH would benefit patients affected by heart failure. Indeed, GH and/or IGF-1 have proven beneficial in various models of experimental heart failure. Tested in patients with classes II-IV heart failure, they improved cardiac performance and clinical status. These effects were associated with improved myocardial energetics and de-activation of the neurohormonal system. Because of the uncontrolled nature of the studies and the small number of cases examined, conclusions as to the effectiveness of GH and IGF-1 must await the results from larger trials.