BACKGROUND AND AIMS: Healthy individuals counteract insulin-induced hypoglycaemia by increasing glutamine utilization but not proteolysis. Glucagon is important to this response because it increases glutamine uptake. In type 1 diabetes (T1DM) glucagon and epinephrine responses to hypoglycaemia are defective. We investigated whether glutamine and amino acid utilization during hypoglycaemia is altered in T1DM with defective counter-regulatory responses. METHODS AND RESULTS: Eight T1DM patients (duration of diabetes 14+/-4years and therefore with presumed defective counter-regulatory response) and eight controls (CON) received a 3h hypoglycaemic hyperinsulinaemic (0.65mU/kg per min) clamp coupled to [6,6-(2)H(2)]glucose, [1-(13)C]leucine and [2-(15)N]glutamine to trace the relative kinetics. Post-absorptive plasma glucose and glucose uptake were increased in T1DM (9.09+/-0.99 vs 5.01+/-0.22mmol/l and 19.5+/-0.9 vs 12.6+/-0.8mumol/kg per min, p<0.01). During the clamp T1DM but not CON required exogenous glucose (4.4+/-1.7mumol/kg per min) to maintain the hypoglycaemic plateau because the endogenous glucose production was significantly suppressed (p<0.01). In T1DM the leucine and phenylalanine concentrations were less suppressed from basal (p<0.05) despite a similar insulin suppression of proteolysis (-16+/-2 vs -20+/-4%, p=ns) indicating a defective stimulation of leucine metabolic clearance from basal (+18+/-3% vs +55+/-9%, p<0.01). Glutamine concentration remained unchanged from basal (-7+/-3% vs -35+/-3%, p<0.01) and the clearance of glutamine was markedly defective in T1DM (+6+/-2%) in comparison with controls (+22+/-4%; p=0.02). CONCLUSIONS: In T1DM, the counter-regulatory failure to hypoglycaemia seems to be associated with a defective glutamine utilization. The failure to clear circulating amino acids, specifically glutamine, during hypoglycaemia may adversely affect gluconeogenesis.

Protein and glutamine kinetics during counterregulatory failure in type 1 diabetes / A. Battezzati, S. Benedini, L. Piceni Sereni, F. De Taddeo, P. Maffi, A. Secchi, L. Luzi. - In: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. - ISSN 0939-4753. - 19:5(2009 Jun), pp. 352-357.

Protein and glutamine kinetics during counterregulatory failure in type 1 diabetes

A. Battezzati
Primo
;
S. Benedini
Secondo
;
A. Secchi
Penultimo
;
L. Luzi
Ultimo
2009

Abstract

BACKGROUND AND AIMS: Healthy individuals counteract insulin-induced hypoglycaemia by increasing glutamine utilization but not proteolysis. Glucagon is important to this response because it increases glutamine uptake. In type 1 diabetes (T1DM) glucagon and epinephrine responses to hypoglycaemia are defective. We investigated whether glutamine and amino acid utilization during hypoglycaemia is altered in T1DM with defective counter-regulatory responses. METHODS AND RESULTS: Eight T1DM patients (duration of diabetes 14+/-4years and therefore with presumed defective counter-regulatory response) and eight controls (CON) received a 3h hypoglycaemic hyperinsulinaemic (0.65mU/kg per min) clamp coupled to [6,6-(2)H(2)]glucose, [1-(13)C]leucine and [2-(15)N]glutamine to trace the relative kinetics. Post-absorptive plasma glucose and glucose uptake were increased in T1DM (9.09+/-0.99 vs 5.01+/-0.22mmol/l and 19.5+/-0.9 vs 12.6+/-0.8mumol/kg per min, p<0.01). During the clamp T1DM but not CON required exogenous glucose (4.4+/-1.7mumol/kg per min) to maintain the hypoglycaemic plateau because the endogenous glucose production was significantly suppressed (p<0.01). In T1DM the leucine and phenylalanine concentrations were less suppressed from basal (p<0.05) despite a similar insulin suppression of proteolysis (-16+/-2 vs -20+/-4%, p=ns) indicating a defective stimulation of leucine metabolic clearance from basal (+18+/-3% vs +55+/-9%, p<0.01). Glutamine concentration remained unchanged from basal (-7+/-3% vs -35+/-3%, p<0.01) and the clearance of glutamine was markedly defective in T1DM (+6+/-2%) in comparison with controls (+22+/-4%; p=0.02). CONCLUSIONS: In T1DM, the counter-regulatory failure to hypoglycaemia seems to be associated with a defective glutamine utilization. The failure to clear circulating amino acids, specifically glutamine, during hypoglycaemia may adversely affect gluconeogenesis.
Hypoglycaemia ; Glutamine ; Gluconeogenesis ; Glucagon
Settore MED/13 - Endocrinologia
Settore BIO/09 - Fisiologia
giu-2009
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/61390
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 6
social impact