The Intricate Role of Growth Hormone in Metabolism

Growth hormone (GH), a master regulator of somatic growth, also regulates carbohydrate and lipid metabolism via complex interactions with insulin and insulin-like growth factor-1 (IGF-1). Data from human and rodent studies reveal the importance of GH in insulin synthesis and secretion, lipid metabolism and body fat remodeling. In this review, we will summarize the tissue-specific metabolic effects of GH, with emphasis on recent targets identified to mediate these effects. Furthermore, we will discuss what role GH plays in obesity and present possible mechanisms by which this may occur

Synthesis: Deriving a Core Set of Recommendations to Optimize Diabetes Care on a Global Scale

Background: Diabetes afflicts 382 million people worldwide, with increasing prevalence rates and adverse effects on health, well-being, and society in general. There are many drivers for the complex presentation of diabetes, including environmental and genetic/epigenetic factors. Objective: The aim was to synthesize a core set of recommendations from information from 14 countries that can be used to optimize diabetes care on a global scale. Methods: Information from 14 papers in this special issue of Annals of 'Global Health' was reviewed, analyzed, and sorted to synthesize recommendations. PubMed was searched for relevant studies on diabetes and global health. Findings: Key findings are as follows: (1) Population-based transitions distinguish region-specific diabetes care; (2) biological drivers for diabetes differ among various populations and need to be clarified scientifically; (3) principal resource availability determines quality-of-care metrics; and (4) governmental involvement, independent of economic barriers, improves the contextualization of diabetes care. Core recommendations are as follows: (1) Each nation should assess region-specific epidemiology, the scientific evidence base, and population-based transitions to establish risk-stratified guidelines for diagnosis and therapeutic interventions; (2) each nation should establish a public health imperative to provide tools and funding to successfully implement these guidelines; and (3) each nation should commit to education and research to optimize recommendations for a durable effect. Conclusions: Systematic acquisition of information about diabetes care can be analyzed, extrapolated, and then used to provide a core set of actionable recommendations that may be further studied and implemented to improve diabetes care on a global scale

CD24 cell surface expression in Mvt1 mammary cancer cells serves as a biomarker for sensitivity to anti-IGF1R therapy

IGF1R-KD significantly reduced the metastatic capacity of CD24+ cells. (A) Representation of lung metastasis following 4 weeks of 10,000 cells inoculation into WT mice tail vein. (B) Average of macrometastasis per lung in each group is displayed in the bar graph. Mann-Whitney test performed to compare the difference between the groups. **P < 0.005. (PPTX 537 kb

High-Efficient FLPo Deleter Mice in C57BL/6J Background

Conditional gene manipulation in mice becomes a routine for genetic studies of mammalian gene functions. Additional site-specific recombinases such as FLP or φ31 provide one more level of gene manipulation flexibility. The recombination activity of the currently available FLP deleter mice remains low. We generated a new FLP deleter mouse line with the mouse codon-optimized FLPo gene in C57BJ/6 background, which showed superior recombination efficacy in comparison to FLPe deleter mice. 100% complete removal of FRT-flanked Neo cassette was observed in all F1 progeny mice carrying both FLPo and Neo cassette, which can be transmitted to F2 generation independent of FLPo activity. Our new FLPo transgenic mice (on pure C57BJ/6 background) will largely facilitate the gene targeting process and is valuable for conditional gene manipulation

Fibronectin glycation increases IGF-I induced proliferation of human aortic smooth muscle cells

The advanced glycation end products, namely AGEs, contribute to long-termed complications of diabetes mellitus, including macroangiopathy, where smooth muscle cells (SMC) proliferation stimulated by platelet-derived growth factor (PDGF) isoforms and insulin-like growth factor-I (IGF-I) plays an important role. The objective of the present study was to investigate the effect of an AGE-modified extracellular matrix protein on IGF-I induced SMC proliferation and on the IGF-I-IGF binding protein 4 (IGFBP-4) axis under basal conditions and after stimulation with PDGF-BB. IGF-I resulted in significantly higher thymidine incorporation in SMC seeded on AGE-modified fibronectin (AGE-FN) in comparison to cells seeded on fibronectin (FN). This augmented proliferation could not be accounted for by increased expression of IGF-IR, by decreased secretion of IGFBP-4, a binding protein that inhibits IGF-I mitogenic effects or by increased IGF-IR autophosphorylation. PDGF-BB did not modulate IGF-IR and IGFBP-4 mRNA expression in any of the substrata, however, this growth factor elicited opposite effects on the IGFBP-4 content in the conditioned media, increasing it in cells plated on FN and diminishing it in cells plated on AGE-FN. These findings suggest that one mechanism by which AGE-modified proteins is involved in the pathogenesis of diabetes-associated atherosclerosis might be by increasing SMC susceptibility to IGF-I mitogenic effects.FAPESP, Sao Paulo, Brazil [91/3617-8]FAPESP (Sao Paulo, Brazil

Activating Transcription Factor-5 Knockdown Reduces Aggressiveness of Mammary Tumor Cells and Attenuates Mammary Tumor Growth

Activating transcription factor-5 (ATF5) is an anti-apoptotic factor and has been implicated in enhancing the survival of cancer cells under stress and in regulating the autophagy process. Targeting ATF5 in anticancer therapy may be particularly attractive because of its differential role in cancer cells than in non-transformed cells, thus allowing specificity of the treatment. Using the delivery of short hairpin RNA vectors into the Mvt1 and Met1 cell lines, we tested the role of ATF5 in the development of mammary tumors in vivo and in regulating proliferation and migration of these cells in vitro. In this study, we demonstrate that knockdown of ATF5 (ATF5-KD) in both cell lines results in a decreased tumor volume and weight, as well as in a reduced proliferation rate and migratory potential of the cells. In addition, ATF5-KD led to an increased autophagy flux and a shift in the sub-populations comprising Mvt1 cells from the aggressive CD24-positive cells toward less aggressive CD24-negative cells. Taken together, these findings suggest that ATF5 plays an important role in enhancing mammary tumor cells overall aggressiveness and in promoting mammary tumor growth and emphasize the possible benefit of anti-ATF5 therapy in breast cancer patients, particularly, against tumors characterized with the positive expression of cell surface CD24