دورية أكاديمية
Insulin signaling is preserved in skeletal muscle during early diabetic ketoacidosis
| العنوان: | Insulin signaling is preserved in skeletal muscle during early diabetic ketoacidosis |
|---|---|
| المؤلفون: | Fisker, Frederikke A, Voss, Thomas S, Svart, Mads Vandsted, Kampmann, Ulla, Vendelbo, Mikkel H, Bengtsen, Mads B, Lauritzen, Esben S, Møller, Niels, Jessen, Niels |
| المصدر: | Fisker , F A , Voss , T S , Svart , M V , Kampmann , U , Vendelbo , M H , Bengtsen , M B , Lauritzen , E S , Møller , N & Jessen , N 2024 , ' Insulin signaling is preserved in skeletal muscle during early diabetic ketoacidosis ' , The Journal of Clinical Endocrinology & Metabolism , vol. 109 , no. 1 , pp. e155-e162 . https://doi.org/10.1210/clinem/dgad464Test |
| سنة النشر: | 2024 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | Diabetes Mellitus, Type 1/drug therapy, Diabetic Ketoacidosis/metabolism, Glucose/metabolism, Glycogen Synthase/metabolism, Humans, Insulin Resistance/physiology, Insulin/metabolism, Muscle, Skeletal/metabolism, Signal Transduction, diabetic ketoacidosis, insulin action, skeletal muscle, Cross-Over Studies |
| الوصف: | BACKGROUND AND AIMS: During diabetic ketoacidosis (DKA), muscle tissue develops a profound insulin resistance and this complicates reversal of this potentially lethal condition. We have investigated mediators of insulin action in human skeletal muscle during total insulin withdrawal (IW) in patients with type 1 diabetes, under the hypothesis that initial phases of DKA are associated with impaired post-receptor signaling. MATERIALS AND METHODS: Muscle biopsies were obtained during a randomized, controlled, crossover trial involving nine 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 IW, insulin-stimulated de-phosphorylation of glycogen synthase (GS) was decreased by ∼ 30% (p<0.05) compared to the control situation. This was associated with a decrease in glucose oxidation by ∼ 30% (p<0.05). Despite alterations in glucose metabolism, insulin transduction to glucose transport and protein synthesis (Akt, AS160, mTOR and 4eBP1) was intact, and glucose transporter (GLUT4) and mitochondrial proteins (SDHA and PHB1) protein expression were unaffected by the intervention. CONCLUSION: Diabetic ketoacidosis (DKA) impairs insulin-stimulated activation of GS while insulin signal transduction to glucose transport and protein synthesis remains intact. Reversal of insulin resistance during treatment of DKA should target post-receptor mediators of glucose uptake. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://pure.au.dk/portal/en/publications/8d689845-53c1-4a1f-9a9a-ba19116c1e7bTest |
| DOI: | 10.1210/clinem/dgad464 |
| الإتاحة: | https://doi.org/10.1210/clinem/dgad464Test https://pure.au.dk/portal/en/publications/8d689845-53c1-4a1f-9a9a-ba19116c1e7bTest http://www.scopus.com/inward/record.url?scp=85181176592&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.70EE5B19 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1210/clinem/dgad464 |
|---|