Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans: Effects of acute insulin withdrawal

N. Moller, Michael Dennis Jensen, R. A. Rizza, J. C. Andrews, K Sreekumaran Nair

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1901-1908
Number of pages8
JournalDiabetologia
Volume49
Issue number8
DOIs
StatePublished - Aug 2006

Fingerprint

Leucine
Fats
Insulin
Phenylalanine
Kidney
Amino Acids
Glucose
Tyrosine
Palmitates
Leg
Renal Veins
Femoral Vein
C-Peptide
Femoral Artery
Type 1 Diabetes Mellitus
Fatty Acids
Proteins

Keywords

  • Arteriovenous kidney and leg technique
  • Glucose
  • Indirect calorimetry
  • Leucine
  • Palmitate
  • Tracers

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Renal amino acid, fat and glucose metabolism in type 1 diabetic and non-diabetic humans : Effects of acute insulin withdrawal. / Moller, N.; Jensen, Michael Dennis; Rizza, R. A.; Andrews, J. C.; Nair, K Sreekumaran.

In: Diabetologia, Vol. 49, No. 8, 08.2006, p. 1901-1908.

Research output: Contribution to journalArticle

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abstract = "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.",
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T2 - Effects of acute insulin withdrawal

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AU - Jensen, Michael Dennis

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AU - Andrews, J. C.

AU - Nair, K Sreekumaran

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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.

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KW - Tracers

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