title: Reciprocal regulation of insulin and plasma 5'-AMP in glucose homeostasis in mice.
abstract: A previous investigation has demonstrated that plasma 5'-AMP (pAMP) exacerbates and causes hyperglycemia in diabetic mice. However, the crosstalk between pAMP and insulin signaling to regulate glucose homeostasis has not been investigated in depth. In this study, we showed that the blood glucose level was more dependent on the ratio of insulin to pAMP than on the absolute level of these two factors. Administration of 5'-AMP significantly attenuated the insulin-stimulated insulin receptor (IR) autophosphorylation in the liver and muscle tissues, resulting in the inhibition of downstream AKT phosphorylation. A docking analysis indicated that adenosine was a potential inhibitor of IR tyrosine kinase. Moreover, the 5'-AMP treatment elevated the ATP level in the pancreas and in the isolated islets, stimulating insulin secretion and increasing the plasma level of insulin. The insulin administration decreased the 5'-AMP-induced hyper-adenosine level by the up-regulation of adenosine kinase activities. Our results indicate that blood glucose homeostasis is reciprocally regulated by pAMP and insulin.
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Yibei
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Molecular MetabolismNanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, ChinaDepartment of RadiologyNanjing University of Chinese Medicine, Nanjing 210000, ChinaDepartment of Biochemistry and Molecular BiologyJiangsu University School of Medicine, Zhenjiang 212013, China jfzhang@mail.njust.edu.cn.
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002478:Cells, Cultured; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000241:Adenosine
keywords: 5′-AMP; glucose homeostasis; hyper-adenosine; insulin; insulin receptor; phosphorylation