Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: effects of acute insulin withdrawal.
OBJECTIVE
The aim of this study was to test the hypothesis that type 1 diabetes alters renal amino acid, glucose and fatty acid metabolism.


METHODS
We studied five C-peptide-negative, type 1 diabetic subjects during insulin replacement (glucose 5.6 mmol/l) and insulin deprivation (glucose 15.5 mmol/l) and compared them with six non-diabetic subjects. Leucine, phenylalanine, tyrosine, glucose and palmitate tracers were infused after an overnight fast and samples were obtained from the renal vein, femoral vein and femoral artery.


RESULTS
Insulin deprivation significantly increased whole-body fluxes (20-25%) of phenylalanine, tyrosine and leucine, and leucine oxidation (50%). Kidney contributed 5-10% to the whole-body leucine and phenylalanine flux. A net uptake of phenylalanine, conversion of phenylalanine to tyrosine (5 micromol/min) and net release of tyrosine (approximately 5 micromol/min) occurred across the kidney. Whole-body (three-fold) and leg (two-fold) leucine transamination increased but amino acid metabolism in the kidney did not alter with diabetes or insulin deprivation. Insulin deprivation doubled endogenous glucose production, renal glucose production was unaltered by insulin deprivation and diabetes (ranging between 100 and 140 micromol/min). Renal palmitate exchange was unaltered by insulin deprivation.


CONCLUSIONS
In conclusion, kidney post-absorptively accounts for 5-10% of whole-body protein turnover, 15-20% of leucine transamination and 10-15% of endogenous glucose production, and actively converts phenylalanine to tyrosine. During insulin deprivation, leg becomes a major site for leucine transamination but insulin deprivation does not affect renal phenylalanine, leucine, palmitate or glucose metabolism. Despite its key metabolic role, insulin deprivation in type 1 diabetic patients does not alter many of these metabolic functions.
Moller
N
N
Endocrine Research Unit, Mayo Clinic College of Medicine, 200 First Street SW, 5-194 Joseph, Rochester, MN 55905, USA.
Jensen
M D
MD
Rizza
R A
RA
Andrews
J C
JC
Nair
K S
KS
D000596:Amino Acids / Q000378:metabolism*; D001783:Blood Flow Velocity; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D012016:Reference Values; D012079:Renal Circulation; D013375:Substance Withdrawal Syndrome; D014443:Tyrosine / Q000378:metabolism
D000596:Amino Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D019308:Palmitic Acid; D014443:Tyrosine; D010649:Phenylalanine; D007930:Leucine; D005947:Glucose