Can insulin administration cause an acute metabolic acidosis in vivo? An experimental study in dogs.
Insulin is the cornerstone of therapy for diabetic ketoacidosis because it causes the rate of ketoacid production to fall; this action takes several hours to occur. Insulin also causes H+ to be transported from the intracellular fluid to the extracellular fluid in vitro. The purpose of this study was to determine if insulin led to the acute export of H+ from the intracellular fluid in vivo. If so, we wished to determine if this also occurred during chronic metabolic acidosis, to quantitate the magnitude of the H+ shift, and to evaluate the mechanisms involved. The administration of low- or high-dose insulin to normal dogs and high-dose insulin to dogs with chronic metabolic acidosis caused the concentration of bicarbonate in plasma to decline by close to 3 mmol/l. The PCO2 fell by close to 15% in all three groups of dogs, so one component of the fall was due to hyperventilation. As the pH of blood did not change, a primary metabolic acidosis also occurred. The fall in bicarbonataemia was not due to net accumulation of organic acids or to a loss of bicarbonate or organic anions in the urine. Taken together, insulin, when given at doses used to treat diabetic ketoacidosis, might induce a significantly greater degree of acidaemia in the extracellular fluid acutely after it is given.
Goguen
J M
JM
Division of Nephrology, St Michael's Hospital, University of Toronto, Canada.
Halperin
M L
ML
D000138:Acidosis / Q000097:blood / Q000139:chemically induced* / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000633:toxicity*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010313:Partial Pressure
D001639:Bicarbonates; D001786:Blood Glucose; D007328:Insulin; D002245:Carbon Dioxide