title: The Characteristics of Hepatic Gsα-cAMP Axis in HSHF Diet-Fed Obese Insulin Resistance Rats and Genetic Diabetic Mice.
abstract: Stimulatory G protein α-subunit (Gsα) mediated cAMP signal is required for elevated hepatic glucose production (HGP) in diabetic patients. However, it remains obscure of the exact characteristics of hepatic Gsα-cAMP signal axis (including Gsα, glucagon receptor, β2-adrenergic receptor, cAMP, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). In current study, we investigated the changing characteristics of hepatic Gsα-cAMP signal axis and blood glucose in high-sugar-high-fat (HSHF)-diet-induced IR Wistar rats and db/db diabetic mice. As expected, the HSHF-diet rats were characterized by hyperinsulinemia, hyperglycemia and impaired glucose tolerance. According to a threshold (1.7) of homeostasis model assessment ratio (HOMA-R), the process of IR in HSHF-diet rats could be divided into slight and high IR stages, with the week-23 as the cut-off point. In early slight IR stage, key molecules expressions of hepatic Gsα-cAMP signal axis in HSHF-diet rats were up-regulated with significantly elevated fasting blood glucose (FBG) from 18 to 23 weeks. Unexpectedly, in high IR stage, hepatic Gsα-cAMP signal axis was recovered comparatively to that of normal chow-diet rats, and no significant differences in FBG levels were found. However, in diabetic db/db mice, up-regulation of hepatic Gsα-cAMP signal axis was responsible for its severely increased fasting hyperglycaemia. Our data revealed a positive correlation between hepatic Gsα-cAMP signal axis and FBG in slight IR stage of HSHF-diet rats and diabetic db/db mice. The current finding thus suggested hepatic Gsα-cAMP signal axis plays a central role in regulating of FBG during the developing and development of T2DM.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology.|State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College.
authors.forename: Nina
authors.initials: N
authors.lastname: Xue
authors.affiliation: Beijing Institute of Pharmacology and Toxicology.
authors.forename: Chen
authors.initials: C
authors.lastname: Wei
authors.affiliation: Beijing Institute of Pharmacology and Toxicology.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology.
authors.forename: Hongying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Stomatology, The Fourth Military Medical University.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D000242:Cyclic AMP / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D059305:Diet, High-Fat; D000073417:Dietary Sugars; D004195:Disease Models, Animal; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D000073417:Dietary Sugars; D044385:GTP-Binding Protein alpha Subunits; D007328:Insulin; D005934:Glucagon; D000242:Cyclic AMP
keywords: fasting blood glucose; hepatic glucose production; insulin resistance; stimulatory Gα signal axis; type 2 diabetes mellitus