Carbohydrate and lipid metabolism of the renal tubule in diabetes mellitus.
Diabetic nephropathy not only involves vascular and glomerular changes but also affects tubular metabolism, structure and function. Under acute insulin withdrawal the tubular size increases with glomerular hyperfiltration. Insulin like growth factor 1 (IGF1) has been found to be a candidate mediator involved under these conditions. Tubular carbohydrate metabolism is characterized by gluconeogenesis in the proximal tubule, glycolytic enzymes in the distal segments and high aldose reductase activity in the structures of the renal papilla. In the diabetic state, gluconeogenesis is stimulated by changes of the acid base status. Mitochondrial glucose oxidation is decreased by inhibition of pyruvate dehydrogenase activity through preferential oxidation of fatty acids and ketone bodies. The increase in glycogen in distal tubule cells and sorbitol accumulated in papillary structures can be explained by the high extracellular glucose supply under diabetic conditions. Fatty acids taken up in excess of tubular energy needs accumulate in the nephron as triacylglycerols, mainly in the proximal convoluted tubule. Fatty acid oxidation is inhibited by ketone bodies in proximal and outer medullary tubules, leading to preferential oxidation of the latter under ketotic conditions. Ammonia formed during tubular metabolism of glutamine increases in metabolic acidosis but is suppressed by ketone bodies, leading to a nitrogen sparing effect of ketone bodies. All acute metabolic derangements are abolished, and normal metabolism reestablished by adequate insulin treatment in vivo.
Guder
W G
WG
Institut für Klinische Chemie, Städtisches Krankenhaus München-Bogenhausen, Germany.
Schmolke
M
M
Wirthensohn
G
G
D000818:Animals; D050260:Carbohydrate Metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D050356:Lipid Metabolism