Regulation of adiponectin receptor gene expression in diabetic mice.
Adiponectin is an adipocyte-derived factor that plays pivotal roles in lipid and glucose metabolism in muscle and liver. The following two adiponectin receptor types were recently identified: AdipoR1 is abundantly expressed in muscle, whereas AdipoR2 is predominantly expressed in the liver. To clarify the regulation of adiponectin receptor gene expression in diabetic states, we examined mRNA levels of AdipoR1 in the muscles of diabetic animals by Northern blotting. The level of AdipoR1 mRNA was increased approximately 2.5-fold in muscle of streptozotocin (STZ) diabetic mice, but the normal level was restored by insulin administration, indicating that insulin has an inhibitory effect on AdipoR1 expression. To confirm this inhibitory effect of insulin, we performed in vitro experiments using C2C12 skeletal muscle cells. Insulin treatment for 24 h decreased AdipoR1 expression by approximately 60% in C2C12 cells. In addition, this effect was mediated by the phosphatidylinositol 3-kinase-dependent pathway rather than the mitogen-activated protein kinase pathway. AdipoR1 expression in insulin-resistant diabetic mice was also investigated. AdipoR1 expression was decreased by 36% in type 2 diabetic obese db/db mice compared with lean mice. In contrast, hepatic AdipoR2 expression was not significantly changed in either STZ mice or genetically obese mice. Our results indicate that regulation of AdipoR1, but not that of AdipoR2, may be involved in glucose and lipid metabolism in diabetic states.
Inukai
Kouichi
K
Division of Endocrinology and Diabetes, Deptartment of Internal Medicine, Saitama Medical School, Saitama 350-0495, Japan. inukai@saitama-med.ac.jp
Nakashima
Youhei
Y
Watanabe
Masaki
M
Takata
Nobuki
N
Sawa
Takahiro
T
Kurihara
Susumu
S
Awata
Takuya
T
Katayama
Shigehiro
S
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005786:Gene Expression Regulation; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013311:Streptozocin
D007328:Insulin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D013311:Streptozocin