Effects of insulin and amino acids on glucose and leucine metabolism in CAPD patients.
This study investigates the basal and insulin-stimulated glucose metabolism, substrate utilization, and protein turnover in eight patients maintained on continuous ambulatory peritoneal dialysis (CAPD) (mean age 39+/-5 yr, body mass index [BMI] 108+/-6) and 14 control subjects (mean age 33+/-4 yr, BMI 103+/-3). Euglycemic insulin clamp studies (180 min) were performed in combination with continuous indirect calorimetry and 1-14C leucine infusion (study I). Postabsorptive glucose oxidation was higher (1.75+/-0.18 versus 1.42+/-0.14 mg/kg per min) and lipid oxidation was lower (0.43+/-0.09 versus 0.61+/-0.12 mg/kg per min) in CAPD patients than in control subjects (P<0.05 versus control subjects). During the last 60 min of euglycemic hyperinsulinemia, the total rate of glucose metabolism was similar in CAPD and control subjects (6.33+/-0.51 versus 6.54+/-0.62 mg/kg per min). Both insulin-stimulated glucose oxidation (2.53+/-0.27 versus 2.64+/-0.37 mg/kg per min) and glucose storage (3.70+/-0.48 versus 3.90+/-0.58 mg/kg per min) were similar in CAPD and control subjects. Basal leucine flux (an index of endogenous proteolysis) was significantly lower in CAPD patients than in control subjects (1.21+/-0.15 versus 1.65+/-0.07 micromol/kg per min). Leucine oxidation (0.13+/-0.02 versus 0.26+/-0.02 micromol/kg per min) and nonoxidative leucine disposal (an index of protein synthesis) (1.09+/-0.16 versus 1.35+/-0.05 micromol/kg per min) were also reduced in CAPD compared with control subjects (P<0.01 versus control subjects). In response to insulin (study I), endogenous leucine flux decreased to 0.83+/-0.08 and 1.05+/-0.05 micromol/kg per min in CAPD and control subjects, respectively (all P<0.01 versus basal). Leucine oxidation declined to 0.06+/-0.01 and to 0.19+/-0.02 micromol/kg per min in CAPD and control subjects, respectively (P<0.01 versus basal). A second insulin clamp was performed in combination with an intravenous amino acid infusion (study II). During insulin plus amino acid administration, nonoxidative leucine disposal rose to 1.23+/-0.17 and 1.42+/-0.09 micromol/kg per min in CAPD and control subjects, respectively (both P<0.05 versus basal, P = NS versus control subjects), and leucine balance, an index of the net amino acid flux into protein, become positive in both groups (0.30+/-0.05 versus 0.40+/-0.07 micromol/kg per min in CAPD and control subjects, respectively) (both P<0.01 versus basal, P = NS versus control subjects). In summary, in CAPD patients: (1) basal glucose oxidation is increased; (2) basal lipid oxidation is decreased; (3) insulin-mediated glucose oxidation and storage are normal; (4) basal leucine flux is reduced; (5) the antiproteolitic action of insulin is normal; and (6) the anabolic response to insulin plus amino acid administration is normal. Uremic patients maintained on CAPD treatment show a preferential utilization of glucose as postabsorptive energy substrate; however, their anabolic response to substrate administration and the sensitivity to insulin are normal.
Castellino
P
P
Istituto di Clinica Medica Generale e Terapia Medica, Universita' di Catania, Italy. pcastellino@ctonline.it
Luzi
L
L
Giordano
M
M
Defronzo
R A
RA
D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D002153:Calorimetry, Indirect; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007651:Keto Acids / Q000097:blood; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D007930:Leucine / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010531:Peritoneal Dialysis, Continuous Ambulatory; D014176:Protein Biosynthesis; D012016:Reference Values
D000596:Amino Acids; D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D007651:Keto Acids; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose