Insulin-mediated changes in PD and glucose uptake after correction of acidosis in humans with CRF.
To test the hypothesis that acidosis contributes to the insulin resistance of chronic renal failure (CRF) and impairs the action of insulin to decrease protein degradation, eight CRF patients were studied using the combined L-[1-13C]leucine-euglycemic clamp technique before (acid) and after (NaHCO3) 4 wk treatment with NaHCO3 (pH: acid 7.29 +/- 0.01 vs. NaHCO3 7.36 +/- 0.01, P < 0.001). Protein degradation (PD) was estimated sequentially from the kinetics of a primed continuous infusion of L-[1-13C]leucine in the basal state and during a hyperinsulinemic euglycemic clamp. Insulin sensitivity was measured during the clamp. The correction of acidosis significantly increased the glucose infusion rate necessary to maintain euglycemia (acid 6.44 +/- 0.89 vs. bicarbonate 7.38 +/- 0.90 mg.kg-1.min-1, P < 0.01) and significantly decreased PD in the basal state (acid 126.4 +/- 8.1 vs. bicarbonate 100.1 +/- 6.9 mumol.kg-1.h-1, P < 0.001). Hyperinsulinemia decreased PD in both studies (acid basal 126.4 +/- 8.1 vs. clamp 96.5 +/- 7.7, P < 0.001; bicarbonate basal 100.1 +/- 6.9 vs. clamp 88.2 +/- 5.5 mumol.kg-1.h-1, P = 0.06), its effect being unaltered by acidosis, with a reduction of 24% before and 12% after the correction of acidosis. In conclusion, acidosis contributes to the insulin resistance of CRF but does not affect the action of insulin on PD.
Department of Medicine, University of Newcastle upon Tyne, United Kingdom.
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D
Reaich
K A
KA
Graham
S M
SM
Channon
C
C
Hetherington
C M
CM
Scrimgeour
R
R
Wilkinson
T H
TH
Goodship
D000138:Acidosis / Q000188:drug therapy* / Q000209:etiology*; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000378:metabolism*; D001639:Bicarbonates / Q000097:blood; D001794:Blood Pressure; D001835:Body Weight; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007930:Leucine / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D017693:Sodium Bicarbonate / Q000627:therapeutic use
D000596:Amino Acids; D001639:Bicarbonates; D017693:Sodium Bicarbonate; D007930:Leucine; D005947:Glucose