title: Can insulin administration cause an acute metabolic acidosis in vivo? An experimental study in dogs.
abstract: 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.
authors.affiliation: Division of Nephrology, St Michael's Hospital, University of Toronto, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Goguen
authors.forename: M L
authors.initials: ML
authors.lastname: Halperin
mesh_terms: 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
chemical_list: D001639:Bicarbonates; D001786:Blood Glucose; D007328:Insulin; D002245:Carbon Dioxide