Gene Expression Profile in Skeletal Muscle of Type 2 Diabetes and the Effect of Insulin Treatment
Article Figures & Tables
Figures
- FIG. 1.
Real-time PCR data (mRNA levels) of GLUT4, IGFBP5, SOD2, UCP-3, and MHC-I in D2− patients (▪) and D2+ patients (□) (mean ± SE percent change from control subjects). The P values were significant for three genes (GLUT4, SOD2, and MHC-I) in the control versus D2− comparison and also for GLUT4 and IGFBP5 in the control versus D2+ comparison. *P < 0.01; #P < 0.05.
Tables
- TABLE 1
Characteristics of subjects
Study population Age (years) BMI (kg/m2) Average glucose (mg/dl) Insulin level (μU/ml) SI (minimum model) Control 52.4 ± 4.1 29.2 ± 1.5 90.0 ± 2.9 5.2 ± 0.1 5.96 ± 1.04* Diabetic Patients (D2−) 52.8 ± 3.5 29.1 ± 1.4 224.0 ± 26.2* 5.8 ± 0.6 1.82 ± 0.62 Diabetic Patients (D2+) 52.8 ± 3.5 29.1 ± 1.4 98.8 ± 6.4 13.5 ± 2.9† 2.37 ± 0.8 Data are means ± SE.
- *
* P < 0.001;
- †
† P < 0.05 vs. other two groups. Five subjects were studied in each group (two men and three women).
- TABLE 2
Differences in gene transcript levels of type 2 diabetic patients (D2−) and insulin-treated type 2 diabetic patients (D2+) in comparison with control subjects
Probe set Fold Δ Gene name A B Structural/contractile HG2743-HT2846 ↑3.3* (↑1.5)† Caldesmon 1 HG1862-HT1897 ↑2.0‡ (↑2.9)§ Calmodulin type I HG2175-HT2245 ↓4.9* (↓1.4)† Myosin heavy chain polypeptide HG2260-HT2349 ↓3.9‖ (↓1.4)† Duchenne Muscular Dystrophy protein M21984 ↓3.2* (↓1.7)† Troponin-T M21665 ↓3.1* (↓1.7)† MHC-I HG3514-HT3708 ↓2.5* (↓1.2)† Tropomyosin (cytoskeletal) X04201 ↓2.4* (↓1.9)* Tropomyosin (1.3 kb) X66276 ↓2.4* (↓2.0)§ Skeletal muscle C-protein L21715 ↓2.3‖ (↓2.1)§ Troponin-I fast-twitch J04760 ↓2.2* (↓2.0)* Troponin-I slow-twitch M20642 ↓2.1‡ (↓1.4)† Myosin light chain M20543 ↓2.0‖ (↓1.5)† Skeletal muscle α-actin U35637 ↓2.0‡ (↓1.5)† Nebulin X13839 ↓1.9‡ (↓1.8)† Smooth muscle α-actin M33772 ↓1.9† (↓2.1)* Troponin-C fast-twitch Mitochondrial maintenance/chaperone X93511 ↓2.4* (↓1.3)† Telomeric DNA binding protein X83416 ↓2.4§ (↓1.4)† PrP V00594 ↓2.2‡ (↓1.6)† MT X82200 ↓2.2‖ (↓1.8)† Staf50 X65965 ↓2.2‖ (↓1.2)† SOD2 HG2855-HT2995 ↑2.0* (↑3.2)* Heat shock protein, 70 kDa Growth factors/tissue development/maintenance L27560 ↑2.5* (↑2.9)* IGFBP-5 M55210 ↓3.9* (↓1.7)† Laminin B2 chain L08246 ↓3.4‡ (↓2.2)§ MCL1 AB000897 ↓2.8‖ (↓2.1)§ Cadherin FIB3 Insulin signaling/signal transduction/glucose metabolism HG2702-HT2798 ↓5.6‖ (↓1.4)† Serine/threonine kinase D23673 ↓2.8* (↓1.3)† IRS-1 L10717 ↑2.9‡ (↓1.3)† T-cell–specific tyrosine kinase L33881 ↓3.1† (↓1.4)† Protein kinase C-ι K03515 ↑2.3‡ (↓1.4)† Neuroleukin J04501 ↓2.4‖ (↓1.6)† Muscle glycogen synthase U27460 ↓2.3* (↓1.2)† UDP-glucose pyrophosphorylase M91463 ↓2.1§ (↓1.3)† GLUT4 M32598 ↓2.0* (↓1.2)† Muscle glycogen phosphorylase Energy metabolism D16480 ↑3.1* (↑1.6)† Mitochondrial enoyl-CoA hydratase D10523 ↑2.3‖ (↑1.2)† 2-Oxoglutarate dehydrogenase AF001787 ↓2.7§ (↓1.4)† UCP-3 X13794 ↓2.7‡ (↓1.4)† Lactate dehydrogenase B M83186 ↓2.5‖ (↓1.7)† COX VIIa M19483 ↓2.4‖ (↓1.4)† ATP synthase β subunit U65579 ↓2.3‡ (↓2.0)‡ NADH dehydrogenase-ubiquinone X69433 ↓2.2‖ (↓1.2)† Mitochondrial isocitrate dehydrogenase U94586 ↓2.2‖ (↑1.2)† NADH-ubiquinone oxidoreductase HG4747-HT5195 ↓2.1* (↓1.1)† NADH-ubiquinone oxidoreductase MLRQ M22760 ↓2.1‡ (↓1.3)† COX Va U09813 ↓2.0§ (↑1.2)† ATP synthase subunit 9 X83218 ↓2.0§ (↓1.1)† ATP synthase U17886 ↓2.0§ (↓1.2)† Succinate dehydrogenase (SDHB) L32977 ↓1.9§ (↑1.4)† Ubiquinol cytochrome C reductase Transcription factors/protein metabolism HG1428-HT1428 ↓2.1‡ (↓1.4)† Globin-β HG3635-HT3845 ↓3.8* (↓1.6)† Zinc finger protein, krupple X69116 ↓3.7* (↓1.7)† Zinc finger protein X16064 ↓2.2* (↓1.5)† Translationally controlled tumor protein U37690 ↓2.0‖ (↓1.3)† RNA polymerase II subunit U95040 ↓2.1‡ (↓1.2)† hKAP1/TIF1B U65928 ↓1.9* (↓1.1)† Jun activation domain binding protein HG3214-HT3391 ↑2.9* (↓1.8)† Metallopanstimulin 1 U73379 ↑2.3‡ (↓1.3)† Cyclin-selective ubiquitin carrier X03689 ↑2.3‡ (↓1.4)† Elongation factor TU M17886 ↓2.1* (↓1.7)† Acidic ribosomal phosphoprotein P1 U49869 ↓2.1* (↓1.5)† Ubiquitin Z21507 ↓2.0‡ (↓1.5)† Elongation factor-1 Δ U14968 ↓1.9‡ (↑1.5)† Ribosomal protein L27a U14973 ↓1.9‡ (↓1.4)† Ribosomal protein S29 A, control versus D2− patients; B, control versus D2+ patients.
- *
* P < 0.01,
- †
† P > 0.05,
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‡ P < 0.05,
- §
§ P < 0.0001,
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‖ P < 0.001, with P values calculated from t test on the average difference between control subjects and D2− (A) or D2+ (B) patients.
- TABLE 3
Additional genes altered in type 2 diabetes (D2− and D2+)
Probe set Fold Δ Gene name Class/function A B HG2239-HT2324 ↑11* (↑1.3)† Potassium channel protein Ion channel U90546 ↑5.8* (↑1.7)† Butyrophilin 4 Immune system X89267 ↑3.6* (↑1.5)† Uroporphyrinogen decarboxylase Heme biosynthesis L24564 ↑3.2‡ (↑1.8)† Rad Ras-oncogene associated with diabetes D43951 ↑3.1§ (↑1.3)† KIAA0099 Unknown D79986 ↑2.3§ (↑1.3)† KIAA0164 Unknown J02611 ↑2.1‡ (↑1.8)† Apolipoprotein D Lipid transport L11238 ↓3.2§ (↓1.6)† Platelet membrane glycoprotein V Homeostasis X59405 ↓3.0‖ (↓1.5)† Membrane cofactor protein Regulatory glycoprotein X63575 ↓2.8‡ (↓1.5)† Calcium ATPase Calcium homeostasis M16714 ↓2.6§ (↓1.6)† MHC I lymphocyte antigen Immune system X00371 ↓2.5* (↓1.8)† Myoglobin Oxygen transport X91103 ↓2.5§ (↓1.2)† Hr44 Immune system X01060 ↓2.4‡ (↓1.6)† Transferrin receptor Iron uptake U90313 ↓2.3§ (↓1.4)† Glutathione-S-transferase Glutathione metabolism X75755 ↓2.3‡ (↓1.3)† PR264 Unknown U33286 ↓2.2§ (↓1.2)† Chromosome segregation gene CAS Cell proliferation/apoptosis X15729 ↓2.1§ (↓1.5)† Nuclear p68 protein Cell poliferation X06700 ↓2.1§ (↓1.7)† Pro-α (III) collagen Extracellular matrix protein AB000220 ↓1.9* (↓1.4)† Semaphorin E Immune system A, control versus D2− patients; B, control versus D2+ patients.
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* P < 0.05,
- †
† P > 0.05,
- ‡
‡ P < 0.001,
- §
§ P < 0.01,
- ‖
‖ P < 0.0001, with P values calculated from t test on the average difference between control subjects and D2− (A) or D2+ (B) patients.
- TABLE 4
Gene transcripts remain unaltered by 10 days of insulin treatment in type 2 diabetic patients
Fold Δ Gene name Structural/contractile genes ↑2.9* Calmodulin Type I ↓2.1* Troponin I fast-twitch ↓2.1† Troponin C fast-twitch ↓2.0* Skeletal muscle C-protein ↓2.0† Troponin I slow-twitch ↓1.9† Tropomyosin Stress response/energy metabolism ↑3.2† Heat shock protein, 70 kDa ↓2.0‡ NADH dehydrogenase-ubiquinone Growth factor/tissue development ↑2.9† IGFBP-5 ↓2.2* MCL1 ↓2.1* Cadherin FIB3 - *
* P < 0.0001,
- †
† P < 0.01,
- ‡
‡ P < 0.05, with P values calculated from t test on the average difference between control and D2+ subjects.
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- TABLE 5
Gene transcripts altered (which was normal in D2−) with 10 days of insulin treatment in type 2 diabetic patients
Fold Δ Gene name Structural/Contractile/ Growth factor ↑2.2* ACTN3 ↑2.1* CO-029 ↓2.7† SM22 ↓2.6* Sarcolipin ↓2.2* β-Tropomyosin ↓1.9‡ Cytoskeletal gamma-actin ↑1.9* IGF-II Protein metabolism/Signal transduction ↑2.0* eIF-4C ↑1.9* Ribosomal protein L21 ↓2.6† Ubiquitin carboxyl terminal hydrolase ↓2.3* Ribosomal protein L37a ↓2.0* Elongation factor 1 alpha-2 ↑2.3* AMP-activated protein kinase ↑2.1* Protein tyrosine phosphatase, alpha ↓2.7† Tyrosine kinase receptor ↓2.5† Adenylyl cyclase Immune system/energy metabolism/cell adhesion ↑2.1* Class II histocompatibility antigen DC-α-chain ↑2.3† HK1 ↓1.9* NDUFV3 ↓3.8* Fibronectin ↓2.4† HSPG2 Tissue development/fatty acid metabolism ↑2.1† Cadherin FIB2 ↓2.4* Fatty acid binding protein Transposition/extracellular matrix/unknown ↑2.0* Transposon-like element ↓2.3* Tenascin-X ↑3.0† GOS2 ↑2.6* H4 Histone ↓2.1* SCAMP1 ↓2.0† Phosphodieaterase 3B - *
* P < 0.01,
- †
† P < 0.0001,
- ‡
‡ P < 0.05; P values were calculated from t test on the average difference between control and D2+ subjects. Metallopanstimulin 1 (↓1.8) was the only gene that showed <1.9-fold alteration in gene expression in D2− or D2+ patients compared with the control subjects, with a statistical significance in the above t test (P = 0.04).
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