Disturbance of inorganic phosphate metabolism in diabetes mellitus: its impact on the development of diabetic late complications.
The pathogenesis of diabetic late complications (DLC) is multifactorial. Studies of mechanisms leading to early functional microvascular changes in retina and kidneys point towards a disturbance in the metabolism of inorganic phosphate (Pi) in diabetes. Since tissue hypoxia and reduced high energy phosphates may be important factors in the development of DLC, the influence of Pi concentration on the metabolism and function of the erythrocytes and renal tubular cells, as well as the relationship of the concentration of Pi to total oxygen consumption, have been reviewed. While extensive research data in non-diabetic conditions support the suggestion, that the Pi concentration is a determining factor in regulation of metabolism and rate of oxygen consumption, diabetes shows the opposite behavior. In diabetes, the highest oxygen consumption is associated with the lowest concentration of Pi. Many conventionally-treated juvenile diabetic patients respond as if their tissues were in a state of chronic hypoxia. A disturbance in phosphate handling occurs in the kidney tubules, where the excessive sodium-dependent glucose entry in diabetics depolarizes the electrochemical sodium gradient and consequently impairs inorganic phosphate reabsorption. Similar changes may occur in other cells and tissues in which glucose entry is not controlled by insulin, and particularly in poorly-regulated diabetic patients in whom long-term vascular complications are more likely.
Ditzel
Jørn
J
Department of Endocrinology, Center for Prevention of Struma and Metabolic Diseases, Aalborg University Hospital, Aarhus University, DK 9000, Aalborg, Denmark.
Lervang
Hans-Henrik
HH
D017668:Age of Onset; D000818:Animals; D048909:Diabetes Complications / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D003920:Diabetes Mellitus / Q000378:metabolism / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D008954:Models, Biological; D010710:Phosphates / Q000378:metabolism*; D010760:Phosphorus Metabolism Disorders / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism; D013997:Time Factors
D010710:Phosphates