The existence of an insulin-stimulated glucose and non-essential but not essential amino acid substrate interaction in diabetic pigs
Autor: | Henk Corbijn, Jan W. Wijdenes, Jan VanderMeulen, Sietse Jan Koopmans, Ruud Dekker |
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Jazyk: | angličtina |
Předmět: |
Swine
niddm protein-metabolism medicine.medical_treatment lcsh:Animal biochemistry Protein metabolism Biochemistry Substrate Specificity Diagnostics & Crisis Organization chemistry.chemical_compound Insulin lcsh:QD415-436 humans Essential amino acid chemistry.chemical_classification Diagnostiek & Crisisorganisatie Amino acid ASG Infectieziekten Adaptation Physiology alanine Wageningen Livestock Research medicine.drug Protein Binding Research Article medicine.medical_specialty mechanism Biology lcsh:Biochemistry resistance Internal medicine Diabetes mellitus medicine Diabetes Mellitus Animals Adaptatiefysiologie lcsh:QP501-801 Molecular Biology Research medicine.disease Streptozotocin sensitivity Randle cycle Endocrinology Glucose gluconeogenesis chemistry Gluconeogenesis kinetics WIAS Amino Acids Essential mellitus Onderzoek |
Zdroj: | BMC Biochemistry, 12 BMC Biochemistry BMC Biochemistry 12 (2011) BMC Biochemistry, Vol 12, Iss 1, p 25 (2011) |
ISSN: | 1471-2091 |
DOI: | 10.1186/1471-2091-12-25 |
Popis: | 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. |
Databáze: | OpenAIRE |
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