Glucose Consumption Levels Research Articles

Relationships between degradability of silk scaffolds and osteogenesis

Bone repairs represent a major focus in orthopedic medicine with biomaterials as a critical aspect of the regenerative process. However, only a limited set of biomaterials are utilized today and few studies relate biomaterial scaffold design to degradation rate and new bone formation. Matching biomaterial remodeling rate towards new bone formation is important in terms of the overall rate and quality of bone regeneration outcomes. We report on the osteogenesis and metabolism of human bone marrow derived mesenchymal stem cells (hMSCs) in 3D silk scaffolds. The scaffolds were prepared with two different degradation rates in order to study relationships between matrix degradation, cell metabolism and bone tissue formation in vitro. SEM, histology, chemical assays, real-time PCR and metabolic analyses were assessed to investigate these relationships. More extensively mineralized ECM formed in the scaffolds designed to degrade more rapidly, based on SEM, von Kossa and type I collagen staining and calcium content. Measures of osteogenic ECM were significantly higher in the more rapidly degrading scaffolds than in the more slowly degrading scaffolds over 56 days of study in vitro. Metabolic analysis, including glucose and lactate levels, confirmed the degradation rate differences with the two types of scaffolds, with the more rapidly degrading scaffolds supporting higher levels of glucose consumption and lactate synthesis by the hMSCs upon osteogenesis, in comparison to the more slowly degrading scaffolds. The results demonstrate that scaffold degradation rates directly impact the metabolism of hMSCs, and in turn the rate of osteogenesis. An understanding of the interplay between cellular metabolism and scaffold degradability should aid in the more rational design of scaffolds for bone regeneration needs both in vitro and in vivo.

Regulation of prostate cancer cell division by glucose.

Previous studies have shown that rapid cell proliferation is associated with elevated glucose consumption. However, those studies did not establish whether glucose is required for prostate cancer cell proliferation or define the molecular mechanisms by which glucose regulates cell division. We addressed these issues by studying two metastatic human prostate cancer cell lines: DU145, which is androgen independent and highly proliferative; and LNCaP, which is androgen dependent and relatively slow growing. We found that proliferation of DU145 cells was significantly inhibited by reduction of glucose in the medium to 0.5 g/L, which is half the physiologic concentration, whereas LNCaP cells grew at control rates even in the presence of only 0.05 g/L glucose. Glucose deprivation of DU145 cells caused a 90% reduction in DNA synthesis; a 10-20-fold reduction in cyclins D and E and CDK4 levels; and cell cycle arrest in G0-G1. However, glucose deprivation did not cause global inhibition of protein synthesis, since mutant p53 levels increased in glucose-deprived DU145 cells. This observed increase in mutant p53 levels was not associated with a rise in p21 levels. Glucose deprivation of DU145 cells also led to apparent dephosphorylation of mutant retinoblastoma (RB) protein. We conclude that: 1) high levels of glucose consumption are required for rapid proliferation of androgen-independent prostate cancer cells, 2) glucose may not be required for slow growth of androgen-dependent prostate cancer cells, and 3) glucose promotes passage of cells through early G1 by increasing the expression of several key cell cycle regulatory proteins that normally inhibit RB function.

Hypoxic-ischemic encephalopathy in areas of primary myelination: a neuroimaging and PET study

The stage of regional structural and biochemical development of the central nervous system appears as a critical factor determining the distribution of hypoxic-ischemic lesions during the perinatal period. We describe the brain lesions in 12 patients who suffered hypoxia-ischemia during the perinatal period. The gestational age ranged from 35 to 42 weeks and the age at death from 2 to 16 weeks. There is one patient alive at age 18 years and a second patient at age 1 year. The cerebral cortical damage is mainly restricted to areas of primary myelination and adjacent subcortical white matter. In addition, there is thalamic, basal ganglia, brainstem, and spinal cord damage. It is postulated that selective damage occurs in those areas which at the moment of the hypoxic-ischemic insult had achieved higher rates of oxygen-glucose utilization. This hypothesis is supported by studies utilizing positron emission tomography which indicates that glucose utilization in the normal human neonatal brain follows a phylogenetic order. Regions that achieved higher levels of glucose consumption are those that suffered the brunt of the damage in our term neonates.

Vertical and horizontal visual whole-field motion differently affect the metabolic activity of the rat medial terminal nucleus

The metabolic activity of the medial terminal nucleus (MTN) of the Accessory Optic System was studied by means of the [ 14C]2-deoxyglucose (2-DG) method in Long-Evans rats exposed to moving and stationary visual stimuli. In particular we explored the rate of local cerebral glucose utilization (LCGU) and the spatial distribution of 2-DG uptake within MTN related to visual stimuli capable of triggering optokinetic nystagmus. It was found that increases in MTN metabolism accompanied the retinal slip signals evoked by whole-field visual patterns moving in the vertical as well as in the horizontal direction. At the same level of luminous flux neither the same but stationary pattern, nor constant, diffuse illumination were able to elicit comparable changes in MTN metabolic rates. The effects of vertical and horizontal motions differed, however, from each other. In binocular testing LCGU rates resulted significantly higher after vertically moving patterns and upon the same stimulus condition the spatial distribution of 2-DG matched very closely the spatial distribution of the retinal afferents and the cellular density within MTN, in sharp contrast with the diffuse spreading out of the label across the nucleus following horizontal motion. In monocular testings only the vertically moving patterns were able to increase LCGU rates significantly and then in contralateral MTN alone. However, comparison between the levels of glucose consumption measured in binocular and in monocular vision also showed the involvement of the uncrossed retinal path in relaying the retinal slip signals to MTN. No difference in LCGU and in spatial distribution of the label were finally observed in relation to the upward or to the downward direction of the moving pattern.