Abstract
BackgroundThe 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.ResultsDiabetic 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).ConclusionsThe 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.
Highlights
The generation of energy from glucose is impaired in diabetes and can be compensated by other substrates like fatty acids (Randle cycle)
The ratio of insulin-stimulated glucose versus amino acids (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
This study demonstrates that in diabetic pigs insulin resistance for glucose utilization is accompanied by insulin hypersensitivity for non-essential AA utilization
Summary
The generation of energy from glucose is impaired in diabetes and can be compensated by other substrates like fatty acids (Randle cycle). The interaction between glucose and nonesterified fatty acids (NEFA) for oxidation in tissues or at the whole body level has been documented in many animal and human studies [1,2,3]. The glucose - NEFA cycle was first described by Randle and coworkers [4]. In essence they showed that the metabolic relationship between the substrates glucose and NEFA is reciprocal and not dependent. The purpose of substrate competition is to meet the energy demand of the body by oxidation of different substrates, i.e. glucose, NEFA or AA, depending on the availability of the substrates. After a meal, when plasma glucose, AA, and insulin levels are high, glucose and to a lesser extent AA will be oxidized
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
