title: Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance.
abstract: Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications, and stress proteins have been shown to protect organisms in vitro and in vivo against oxidative stress. To study the putative role of one of the most abundant cytoprotective stress proteins, inducible cytoplasmic 72-kDa-mass heat shock protein (Hsp-72), in the pathogenesis of diabetes, we measured its mRNA concentration in muscle biopsies from six type 2 diabetic patients and six healthy control subjects (protocol 1) as well as in 12 twin pairs discordant for type 2 diabetes and 12 control subjects undergoing a euglycemic-hyperinsulinemic clamp in combination with indirect calorimetry (protocol 2). The amount of Hsp-72 mRNA in muscle was significantly lower in type 2 diabetic patients than in healthy control subjects (in protocol 1: 5.2 +/- 2.2 vs. 53 +/- 32 million copies of Hsp-72 mRNA/microg total RNA, n = 6, P = 0.0039; in protocol 2: 3.2 +/- 3.3 vs. 43 +/- 31 million copies of Hsp-72 mRNA/microg total RNA, n = 12, P = 0.0001). Hsp-72 mRNA levels were also markedly reduced in the nondiabetic co-twins compared with healthy control subjects (5.8 +/- 5.0 vs. 43 +/- 31, n = 12, P = 0.0001), but they were also statistically significantly different from their diabetic co-twins when the difference between the pairs was compared (P = 0.0280). Heat shock protein mRNA content in muscle of examined patients correlated with the rate of glucose uptake and other measures of insulin-stimulated carbohydrate and lipid metabolism. In conclusion, the finding of decreased levels of Hsp-72 mRNA in skeletal muscle of patients with type 2 diabetes and its relationship with insulin resistance raises the question of whether heat shock proteins are involved in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetes.
authors.affiliation: Department of Cellular Biology, BIOREX Research and Development, Veszprem, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Kurucz
authors.forename: Agota
authors.initials: A
authors.lastname: Morva
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Karl-Fredrik
authors.initials: KF
authors.lastname: Eriksson
authors.forename: Xudong
authors.initials: X
authors.lastname: Huang
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Laszlo
authors.initials: L
authors.lastname: Koranyi
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005215:Fasting; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic
chemical_list: D001786:Blood Glucose; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose