Disturbance of inorganic phosphate metabolism in diabetes mellitus: clinical manifestations of phosphorus-depletion syndrome during recovery from diabetic ketoacidosis

The acute effects of intracellular phosphate depletion and hypophosphatemia on organs and tissues in and during recovery from diabetic ketoacidosis (DKA) have been reviewed. When insufficient phosphate and/or oxygen are available for high energy phosphate synthesis, cell homeostasis cannot be maintained and cell integrity may be impaired. The clinical consequences are recognized as occasional cause of morbidity and mortality. Although phosphate repletion has not been routinely recommended in the treatment of DKA, physicians should be aware of these clinical conditions and phosphate repletion in such situations should be considered

Lifestyle diseases and cardiovascular risk factors are interrelated to deficiencies of major substrates in ATP synthesis

Recent studies on diabetes and metabolic syndrome indicate a common disturbance of inorganic phosphate (Pi) metabolism. Pi is an important substrate in the formation of adenosine triphosphate (ATP), and many lifestyle diseases and cardiovascular risk factors similarly show deficiencies in either 1 or 2 major components of ATP synthesis. Age, male gender, hypertension, obesity, hypertriglyceridemia, metabolic syndrome, and diabetes mellitus are all associated with hypophosphatemia. In addition, tobacco smoking, hyperchylomicronemia, hypertension, and diabetes may involve defects in tissue oxygen delivery. Hypophosphatemia may lead to a critical decrease in intracellular Pi and to mitochondrial dysfunction, which might be counter-acted by the pharmacological use of fructose 1,6-diphosphate

Disturbance of inorganic phosphate metabolism in diabetes mellitus: temporary therapeutic intervention trials

A paradoxical metabolic imbalance in inorganic phosphate occurs from the early onset of diabetes and may lead to a reduction of high energy phosphates and tissue hypoxia. These changes take place in the cells and tissues in which the entry of glucose is not controlled by insulin, and particularly in poorly regulated diabetes patients in whom long-term vascular complications are more likely to occur. Several therapeutic intervention trials have been carried out, including assessment of optimal glucose regulation, the effect of dietary inclusion of calcium diphosphate and pharmaceutical intake of etidronate disodium (EHDP), but none of these modalities wholly overcome the problem. The potential therapeutic application of fructose-1, 6-diphosphate, however, which also acts as human bioenergy, holds a great deal of promise as an efficacious and well-tolerated therapeutic regimen

Human DREF/ZBED1 is a nuclear protein widely expressed in multiple cell types derived from all three primary germ layers.

Drosophila DNA replication-related element binding factor (DREF) is a transcription regulatory factor that binds the promoters of many genes involved in replication and cell proliferation and is required for normal cell cycle progression. Human DREF/zinc finger BED domain-containing protein 1 (ZBED1), an orthologue of Drosophila DREF, also has DNA binding activity, but its cellular functions remain largely uncharacterized. Herein, we show that ZBED1 is a chromatin-associated nuclear protein with a wide expression profile in human tissues from all three primary germ layers. For instance, ZBED1 was expressed in mesodermal-derived epithelial cells of the reproductive system and urinary tract, in endodermal-derived epithelial cells throughout the gastrointestinal tract, and in epidermal epithelium from the ectoderm. ZBED1 was also expressed in connective tissue and smooth muscle cells of multiple organs. To investigate whether ZBED1 is implicated in cell proliferation, similar to Drosophila DREF, we compared the tissue distribution of ZBED1 to that of the proliferation marker Ki-67. ZBED1 and Ki-67 were co-expressed in many epithelial tissues, but ZBED1 expression extended widely beyond that of Ki-67-positive cells. In other tissues, ZBED1 expression was more restricted than Ki-67 expression. These results suggest that ZBED1 is not a cell proliferation-associated factor such as Drosophila DREF, and our study adds to the cumulative understanding of the functions of ZBED1 in human cells and tissues