Insulin Signaling Is Preserved in Skeletal Muscle During Early Diabetic Ketoacidosis.
J Clin Endocrinol Metab
; 109(1): e155-e162, 2023 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-37554078
ABSTRACT
BACKGROUND AND AIMS:
During diabetic ketoacidosis (DKA), muscle tissue develops a profound insulin resistance that complicates reversal of this potentially lethal condition. We have investigated mediators of insulin action in human skeletal muscle during total insulin withdrawal in patients with type 1 diabetes, under the hypothesis that initial phases of DKA are associated with impaired postreceptor signaling. MATERIALS ANDMETHODS:
Muscle biopsies were obtained during a randomized, controlled, crossover trial involving 9 patients with type 1 diabetes. The subjects were investigated during a high-dose insulin clamp preceded by either (1) insulin-controlled euglycemia (control) or (2) total insulin withdrawal for 14 hours. Insulin action in skeletal muscle and whole-body substrate metabolism were investigated using western blot analysis and indirect calorimetry respectively.RESULTS:
During insulin withdrawal, insulin-stimulated dephosphorylation of glycogen synthase decreased by â¼30% (P < .05) compared with the control situation. This was associated with a decrease in glucose oxidation by â¼30% (P < .05). Despite alterations in glucose metabolism, insulin transduction to glucose transport and protein synthesis (Akt, AS160, mammalian target of rapamycin, and eukaryotic translation initiation factor 4E binding protein) was intact, and glucose transporter (GLUT4) and mitochondrial proteins (succinate dehydrogenase complex, subunit A and prohibitin 1) protein expression were unaffected by the intervention.CONCLUSION:
DKA impairs insulin-stimulated activation of glycogen synthase, whereas insulin signal transduction to glucose transport and protein synthesis remains intact. Reversal of insulin resistance during treatment of DKA should target postreceptor mediators of glucose uptake. CLINICAL TRIAL REGISTRATION NUMBER NCT02077348.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Cetoacidose Diabética
/
Diabetes Mellitus Tipo 1
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2023
Tipo de documento:
Article