ArticleDiabetologia2012
Hyperglycaemia normalises insulin action on glucose metabolism but not the impaired activation of AKT and glycogen synthase in the skeletal muscle of patients with type 2 diabetes.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Are Individuals With Type 2 Diabetes Metabolically Inflexible? A Systematic Review and Meta-Analysis.Endocrinology, diabetes & metabolism · 2025Pooled it
- Postexercise muscle glycogen synthesis with glucose, galactose, and combined galactose-glucose ingestion.American journal of physiology. Endocrinology and metabolism · 2023Trial
- Trial
- The unfolded protein response and its activation by insulin in muscle are not altered by obesity or type 2 diabetes.Clinical science (London, England : 1979) · 2026Article
- Effect of acute exercise and exercise training on the ability of insulin to clear branched-chain amino acids from plasma in obesity and type 2 diabetes.Diabetologia · 2025Article
- The skeletal muscle response to high-intensity training assessed by single-nucleus RNA-sequencing is blunted in individuals with type 2 diabetes.The Journal of physiology · 2025Article
- HM-chromanone alleviates hyperglycemia and inflammation in mice with endotoxin-induced insulin resistance.Toxicology research · 2023Article
- Intermittent maternofetal oxygenation during late gestation improved birthweight, neonatal growth, body symmetry, and muscle metabolism in intrauterine growth-restricted lambs.Journal of animal science · 2022Article
- Exercise effects on γ3-AMPK activity, phosphorylation of Akt2 and AS160, and insulin-stimulated glucose uptake in insulin-resistant rat skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds.Drug delivery · 2018Article
- ASAS-SSR Triennnial Reproduction Symposium: Looking Back and Moving Forward-How Reproductive Physiology has Evolved: Fetal origins of impaired muscle growth and metabolic dysfunction: Lessons from the heat-stressed pregnant ewe.Journal of animal science · 2018Review
- Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes.Diabetologia · 2017Article
- Gastrointestinal dopamine as an anti-incretin and its possible role in bypass surgery as therapy for type 2 diabetes with associated obesity.Minerva endocrinologica · 2016Review
- Markers of autophagy are adapted to hyperglycaemia in skeletal muscle in type 2 diabetes.Diabetologia · 2015Article
- Dysregulation of muscle glycogen synthase in recovery from exercise in type 2 diabetes.Diabetologia · 2015Article
- Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle.The Journal of physiology · 2014Article
- Minireview: Dopaminergic regulation of insulin secretion from the pancreatic islet.Molecular endocrinology (Baltimore, Md.) · 2013Review
- Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH₂-terminal (sites 2 + 2a) phosphorylation.American journal of physiology. Endocrinology and metabolism · 2013Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIn type 2 diabetes, reduced insulin-stimulated glucose disposal, primarily glycogen synthesis, is associated with defective insulin activation of glycogen synthase (GS) in skeletal muscle. Hyperglycaemia may compensate for these defects, but to what extent it involves improved insulin signalling to glycogen synthesis remains to be clarified.
methodsWhole-body glucose metabolism was studied in 12 patients with type 2 diabetes, and 10 lean and 10 obese non-diabetic controls by means of indirect calorimetry and tracers during a euglycaemic-hyperinsulinaemic clamp. The diabetic patients underwent a second isoglycaemic-hyperinsulinaemic clamp maintaining fasting hyperglycaemia. Muscle biopsies from m. vastus lateralis were obtained before and after the clamp for examination of GS and relevant insulin signalling components.
resultsDuring euglycaemia, insulin-stimulated glucose disposal, glucose oxidation and non-oxidative glucose metabolism were reduced in the diabetic group compared with both control groups (p < 0.05). This was associated with impaired insulin-stimulated GS and AKT2 activity, deficient dephosphorylation at GS sites 2 + 2a, and reduced Thr308 and Ser473 phosphorylation of AKT. When studied under hyperglycaemia, all variables of insulin-stimulated glucose metabolism were normalised compared with the weight-matched controls. However, insulin activation and dephosphorylation (site 2 + 2a) of GS as well as activation of AKT2 and phosphorylation at Thr308 and Ser473 remained impaired (p < 0.05). CONCLUSIONS/INTERPRETATIONS: These data confirm that hyperglycaemia compensates for decreased whole-body glucose disposal in type 2 diabetes. In contrast to previous less well-controlled studies, we provide evidence that the compensatory effect of hyperglycaemia in patients with type 2 diabetes does not involve normalisation of insulin action on GS or upstream signalling in skeletal muscle.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.