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- Karlsson, HKR, et al.
(författare)
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Insulin signaling and glucose transport in skeletal muscle from first-degree relatives of type 2 diabetic patients
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:5, s. 1283-1288
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant insulin signaling and glucose metabolism in skeletal muscle from type 2 diabetic patients may arise from genetic defects and an altered metabolic milieu. We determined insulin action on signal transduction and glucose transport in isolated vastus lateralis skeletal muscle from normal glucose-tolerant first-degree relatives of type 2 diabetic patients (n = 8, 41 ± 3 years, BMI 25.1 ± 0.8 kg/m2) and healthy control subjects (n = 9, 40 ± 2 years, BMI 23.4 ± 0.7 kg/m2) with no family history of diabetes. Basal and submaximal insulin-stimulated (0.6 and 1.2 nmol/l) glucose transport was comparable between groups, whereas the maximal response (120 nmol/l) was 38% lower (P < 0.05) in the relatives. Insulin increased phosphorylation of Akt and Akt substrate of 160 kDa (AS160) in a dose-dependent manner, with comparable responses between groups. AS160 phosphorylation and glucose transport were positively correlated in control subjects (R2 = 0.97, P = 0.01) but not relatives (R2 = 0.46, P = 0.32). mRNA of key transcriptional factors and coregulators of mitochondrial biogenesis were also determined. Skeletal muscle mRNA expression of peroxisome proliferator–activated receptor (PPAR) γ coactivator (PGC)-1α, PGC-1β, PPARδ, nuclear respiratory factor-1, and uncoupling protein-3 was comparable between first-degree relatives and control subjects. In conclusion, the uncoupling of insulin action on Akt/AS160 signaling and glucose transport implicates defective GLUT4 trafficking as an early event in the pathogenesis of type 2 diabetes.
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- Karlsson, HKR, et al.
(författare)
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Relationship between serum amyloid A level and Tanis/SelS mRNA expression in skeletal muscle and adipose tissue from healthy and type 2 diabetic subjects
- 2004
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 53:6, s. 1424-1428
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Tidskriftsartikel (refereegranskat)abstract
- Tanis is a recently described protein reported to be a putative receptor for serum amyloid A and found to be dysregulated with diabetes in the Israeli sand rat Psamommys obesus. Tanis has also been identified as a selenoprotein, one of the first two identified membrane selenoproteins. We determined mRNA expression of the human homologue of Tanis, SelS/AD-015, in skeletal muscle and adipose tissue biopsies obtained from 10 type 2 diabetic patients and 11 age- and weight-matched healthy subjects. Expression of Tanis/SelS mRNA in skeletal muscle and adipose tissue biopsies was similar between diabetic and control subjects. A subset of subjects underwent a euglycemic-hyperinsulinemic clamp, and adipose tissue expression of Tanis/SelS was determined after in vivo insulin stimulation. Adipose tissue Tanis/SelS mRNA expression was unchanged after insulin infusion in control subjects, whereas Tanis/SelS mRNA increased in seven of eight subjects following insulin stimulation in diabetic subjects. Skeletal muscle and adipose tissue Tanis/SelS mRNA expression were positively correlated with plasma serum amyloid A. In conclusion, there is a strong trend toward upregulation of Tanis/SelS following insulin infusion in adipose tissue from type 2 diabetic subjects. Moreover, the positive relationship between Tanis mRNA and the acute-phase protein serum amyloid A suggests an interaction between innate immune system responses and Tanis expression in muscle and adipose tissue.
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