title: Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlation with salt sensitivity in normal subjects.
abstract: BACKGROUND
  Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity.
  
  
  METHODS
  We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method.
  
  
  RESULTS
  During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion.
  
  
  CONCLUSIONS
  Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.
authors.affiliation: Cardiovascular Research School ICaR-VU, Department of Medicine, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: ter Maaten
authors.forename: S J
authors.initials: SJ
authors.lastname: Bakker
authors.forename: E H
authors.initials: EH
authors.lastname: Serné
authors.forename: P M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: R O
authors.initials: RO
authors.lastname: Gans
mesh_terms: D000042:Absorption / Q000187:drug effects; D000328:Adult; D004351:Drug Resistance; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D012965:Sodium Chloride / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D012965:Sodium Chloride