TY - JOUR
T1 - Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans
T2 - Effects of acute insulin withdrawal
AU - Moller, N.
AU - Jensen, M. D.
AU - Rizza, R. A.
AU - Andrews, J. C.
AU - Nair, K. S.
N1 - Funding Information:
Acknowledgements We thank the nursing and dietetic staff of Mayo General Clinical Research Center. We are grateful for the skilful technical assistance of C. Ford, M. Persson, J. Kahl, D. Morse and J. Schimke, and for assistance in the conduct of the study by M. Bigelow. The study is supported by National Institutes of Health grants RO1 DK41973 and MO1 RR00585 and Mayo Foundation. K. S. Nair is David Murdock-Dole Professor of Nutrition at the Mayo Clinic.
PY - 2006/8
Y1 - 2006/8
N2 - Aims/hypothesis: The aim of this study was to test the hypothesis that type 1 diabetes alters renal amino acid, glucose and fatty acid metabolism. Materials and 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 μmol/min) and net release of tyrosine (∼5 μmol/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 μmol/min). Renal palmitate exchange was unaltered by insulin deprivation. Conclusions/ interpretation: In conclusion, kidney postabsorptively 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.
AB - Aims/hypothesis: The aim of this study was to test the hypothesis that type 1 diabetes alters renal amino acid, glucose and fatty acid metabolism. Materials and 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 μmol/min) and net release of tyrosine (∼5 μmol/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 μmol/min). Renal palmitate exchange was unaltered by insulin deprivation. Conclusions/ interpretation: In conclusion, kidney postabsorptively 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.
KW - Arteriovenous kidney and leg technique
KW - Glucose
KW - Indirect calorimetry
KW - Leucine
KW - Palmitate
KW - Tracers
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U2 - 10.1007/s00125-006-0287-3
DO - 10.1007/s00125-006-0287-3
M3 - Article
C2 - 16718465
AN - SCOPUS:33745771552
SN - 0012-186X
VL - 49
SP - 1901
EP - 1908
JO - Diabetologia
JF - Diabetologia
IS - 8
ER -