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AMPK ACTIVATION BY ADIPONECTIN IN RENAL TUBULES OF CONTROL AND DIABETIC RATS
Author(s) -
Cammisotto Philippe G,
Londono Irene,
Gingras Diane,
Bendayan Moise
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1131-d
Subject(s) - ampk , medicine , endocrinology , adiponectin receptor 1 , diabetic nephropathy , adiponectin , glycogen , apoptosis , chemistry , amp activated protein kinase , kidney , diabetes mellitus , biology , protein kinase a , phosphorylation , insulin resistance , biochemistry
Adiponectin and AMPK regulate glucose metabolism and apoptosis. We have examined their role in renal tubules that accumulate glycogen and undergo apoptosis in diabetic nephropathy. Rat kidneys were processed for light microscopy and biochemical determinations. Renal tubules were isolated and incubated in vitro. Western blots were carried out with semi‐quantitative evaluations. Adiponectin receptors ADIPOR1 is present on the luminal side of epithelial cells of distal tubules and thin ascending limb (TAL) in normal and hyperglycaemic rats. ADIPOR2 was not detected. The same cells were positive for catalytic sub‐units α1 and α2, the regulatory sub‐unit β2 and the phosphorylated active form of AMPK. Interestingly, glycogen‐filled tubular cells in tissues of diabetic rats displayed a much lighter staining for active AMPK while ADIPOR1 fluorescence was markedly increased. In vitro incubation of tubules showed that levels of activated AMPK were strongly decreased in hyperglycaemic conditions while total AMPK and ADIPOR1 levels were increased. AICAR and adiponectin potently activated AMPK in tubules from control rats but weakly in those of hyperglycaemic rats. In summary, ADIPOR1 and AMPK are expressed by distal tubules and TAL. Basal and stimulated AMPK activities are decreased in hyperglycaemic conditions. These results suggest that adiponectin resistance develops in renal tubules, which may lead to the accumulation of large glycogen deposits and apoptosis in diabetic nephropathy. (Supported by CIHR).