Abstract:
BACKGROUND:Adiponectin acts as an insulin sensitizer in rodent models. The direct effect of adiponectin in intact type 2 diabetic muscle is unknown. We examined whether adiponectin stimulates glucose transport in isolated skeletal muscle strips from type 2 diabetic men. METHODS:We obtained open muscle biopsies from 12 men with type 2 diabetes (56 +/- 1 years, 30.5 +/- 1.1 kg/m(2)), and from 15 non-diabetic men (59 +/- 1 years, 28.0 +/- 1.0 kg/m(2)). Skeletal muscle strips were isolated and exposed to globular adiponectin (2.5 microg/mL), insulin (120 nM) and/or AICAR (1 mM) in vitro for 1 h. Glucose transport was analysed by accumulation of intracellular 3-O-methyl [(3)H] glucose, phosphorylation of Akt-Ser(473) and Akt-Thr(308) was determined using phosphospecific antibodies, and adiponectin receptor 1 and 2 content was measured using specific antibodies. RESULTS:Globular adiponectin increased glucose transport rate by 1.3-fold (P < 0.01) in type 2 diabetic, but not in non-diabetic muscle. Insulin-stimulated glucose transport rate was unaltered by exposure to globular adiponectin in either group. AICAR increased glucose transport and enhanced insulin-stimulated glucose transport in type 2 diabetic and non-diabetic muscles. Insulin-stimulated phosphorylation of Akt-Ser(473) or Akt-Thr(308) was comparable in type 2 diabetic and non-diabetic muscles, and unaltered by the addition of globular adiponectin in either group. Adiponectin receptor expression was similar in skeletal muscle from type 2 diabetic and non-diabetic men. CONCLUSIONS:Globular adiponectin directly increases glucose transport in skeletal muscle from type 2 diabetic patients. This may occur via Akt-independent signalling routes.
journal_name
Diabetes Metab Res Revjournal_title
Diabetes/metabolism research and reviewsauthors
Kuoppamaa H,Skrobuk P,Sihvo M,Hiukka A,Chibalin AV,Zierath JR,Koistinen HAdoi
10.1002/dmrr.883subject
Has Abstractpub_date
2008-10-01 00:00:00pages
554-62issue
7eissn
1520-7552issn
1520-7560journal_volume
24pub_type
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