Suramin-induced reciprocal changes in glucose and lactate synthesis in renal tubules contribute to its hyperglycaemic action.
Suramin is the drug of choice for the treatment of African trypanosomiasis and onchocerciasis. It is also tested for its potential use as an anticancer agent and chemosensitizer. As suramin has been reported to induce hyperglycaemia, its effect on glucose formation has been studied in isolated rabbit hepatocytes and kidney-cortex tubules. In contrast to hepatocytes, in kidney-cortex tubules suramin augments glucose production and decreases lactate formation. Suramin-induced changes in intracellular gluconeogenic/glycolytic intermediates indicate a decrease in flux through pyruvate-phosphoenolpyruvate step. Moreover, this compound diminishes pyruvate kinase activity in kidney-cortex cytosolic fraction, while fructose-1,6-bisphosphate ameliorates its inhibitory action. As (i) kidneys are important contributors to the whole body glucose homeostasis and (ii) suramin is known to accumulate in kidney, suramin-induced stimulation of glucose formation in renal tubules might be responsible for hyperglycaemia observed in patients undergoing suramin treatment.
Jagielski
Adam K
AK
Department of Metabolic Regulation, Institute of Biochemistry, Warsaw University, I. Miecznikowa 1, 02-096 Warsaw, Poland.
Kryśkiewicz
Edyta
E
Bryła
Jadwiga
J
D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000096:biosynthesis*; D006019:Glycolysis / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D011817:Rabbits; D013498:Suramin / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology
D014344:Trypanocidal Agents; D019344:Lactic Acid; D013498:Suramin; D011770:Pyruvate Kinase; D005947:Glucose