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
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