title: The existence of an insulin-stimulated glucose and non-essential but not essential amino acid substrate interaction in diabetic pigs.
abstract: BACKGROUND
  The generation of energy from glucose is impaired in diabetes and can be compensated by other substrates like fatty acids (Randle cycle). Little information is available on amino acids (AA) as alternative energy-source in diabetes. To study the interaction between insulin-stimulated glucose and AA utilization in normal and diabetic subjects, intraportal hyperinsulinaemic euglycaemic euaminoacidaemic clamp studies were performed in normal (n=8) and streptozotocin (120 mg/kg) induced diabetic (n=7) pigs of ~40-45 kg.
  
  
  RESULTS
  Diabetic vs normal pigs showed basal hyperglycaemia (19.0±2.0 vs 4.7±0.1 mmol/L, P<.001) and at the level of individual AA, basal concentrations of valine and histidine were increased (P<.05) whereas tyrosine, alanine, asparagine, glutamine, glutamate, glycine and serine were decreased (P<.05). During the clamp, diabetic vs normal pigs showed reduced insulin-stimulated glucose clearance (4.4±1.6 vs 16.0±3.0 mL/kg·min, P<.001) but increased AA clearance (166±22 vs 110±13 mL/kg· min, P<.05) at matched arterial euglycaemia (5-7 mmol/L) and euaminoacidaemia (2.8-3.5 mmol/L). The increase in AA clearance was mainly caused by an increase in non-essential AA clearance (93.6±13.8 vs 46.6±5.4 mL/kg·min, P<.01), in particular alanine (14.2±2.4 vs 3.2±0.4 mL/kg·min, P<.001). Essential AA clearance was largely unchanged (72.9±8.5 vs 63.3±8.5 mL/kg· min), however clearances of threonine (P<.05) and tyrosine (P<.01) were increased in diabetic vs normal pigs (8.1±1.3 vs 5.2±0.5, and 14.3±2.5 vs 6.4±0.7 mL/kg· min, respectively).
  
  
  CONCLUSIONS
  The ratio of insulin-stimulated glucose versus AA clearance was decreased 5.4-fold in diabetic pigs, which was caused by a 3.6-fold decrease in glucose clearance and a 2.0-fold increase in non-essential AA clearance. In parallel with the Randle concept (glucose-fatty acid cycle), the present data suggest the existence of a glucose and non-essential AA substrate interaction in diabetic pigs whereby reduced insulin-stimulated glucose clearance seems to be partly compensated by an increase in non-essential AA clearance whereas essential AA are preferentially spared from an increase in clearance.
authors: BioMedical Research of Wageningen University and Research Center, Lelystad, The Netherlands. sietsejan.koopmans@wur.nl
authors: Sietse J
authors: SJ
authors: Koopmans
authors: Jan
authors: J
authors: VanderMeulen
authors: Jan
authors: J
authors: Wijdenes
authors: Henk
authors: H
authors: Corbijn
authors: Ruud
authors: R
authors: Dekker
references: J Clin Invest. 1989 Jul;84(1):205-13
references: 2661589
references: Br J Nutr. 2007 Aug;98(2):237-52
references: 17403271
references: Amino Acids. 2009 May;37(1):1-17
references: 19301095
references: Baillieres Clin Endocrinol Metab. 1993 Oct;7(4):1007-32
references: 8304911
references: Diabetes Metab Rev. 1998 Dec;14(4):263-83
references: 10095997
references: Am J Physiol. 1992 Nov;263(5 Pt 1):E877-83
references: 1443120
references: J Clin Invest. 1986 Jun;77(6):1797-804
references: 3519679
references: J Nutr. 1998 Feb;128(2 Suppl):328S-332S
references: 9478017
references: Diabetologia. 2003 Jul;46(7):917-25
references: 12819901
references: Diabetes. 2002 Mar;51(3):599-605
references: 11872656
references: Eur J Clin Invest. 2005 Jun;35(6):351-4
references: 15948894
references: Science. 1970 Feb 13;167(3920):1003-4
references: 5411169
references: Am J Physiol. 1997 Aug;273(2 Pt 1):E305-14
references: 9277383
references: J Chromatogr. 1994 Jan 14;652(1):90-6
references: 8014233
references: Diabetes. 2002 Aug;51(8):2395-404
references: 12145150
references: Metabolism. 2006 Jul;55(7):960-71
references: 16784971
references: Diabetes Care. 1992 Mar;15(3):318-68
references: 1532777
references: Diabetes. 1993 Dec;42(12):1868-77
references: 8243833
references: Lancet. 1963 Apr 13;1(7285):785-9
references: 13990765
references: Physiol Behav. 2009 Oct 19;98(4):402-10
references: 19615391
references: Horm Metab Res. 2006 Sep;38(9):607-13
references: 16981145
references: Circulation. 2000 Jul 4;102(1):42-7
references: 10880413
references: Am J Physiol. 1996 Mar;270(3 Pt 1):E463-70
references: 8638694
references: Animal. 2010 Jun;4(6):899-920
references: 22444262
references: J Nutr. 1998 Feb;128(2 Suppl):323S-327S
references: 9478016
references: Diabetes. 2008 Jan;57(1):56-63
references: 17940118
references: J Clin Invest. 1990 Dec;86(6):2038-45
references: 2254458
references: Diabetes. 1990 Jan;39(1):38-48
references: 2210059