title: Characterization of the gene expression profile of heterozygous liver-specific glucokinase knockout mice at a young age.
abstract: In the liver, glucokinase (GCK) facilitates hepatic glucose uptake during hyperglycemia and is essential for the regulation of a network of glucose-responsive genes involved in glycolysis, glycogen synthesis, and lipogenesis. To better understand the consequences of changes in response to a liver-specific deficiency of GCK function, we examined the expression profiles of genes involved in glucose metabolism in the liver, pancreas, muscle and adipose tissue in heterozygous liver-specific Gck knockout (Gck(w/-)) mice. Our results showed that with the development of a liver GCK deficiency, significant decreases in the mRNA levels for insulin receptor and Glut2 were observed in the liver, and HkII in muscle, while glucagon mRNA increased markedly in the pancreas. The levels of circulating glucagon hormone levels increased with increased mRNA levels. Depite a decrease in muscle HkII levels, the hexokinase activity level did not change. Our findings suggest that in liver-specific Gck(w/-) mice, peripheral tissues use different strategies to tackle with hyperglycemia even at a young age. By identifying the specific changes that occur in different tissues at an early stage of glucokinase deficiency, potentially we can develop interventions to prevent further progression to diabetes.
authors.affiliation: Department of Pharmacology, Peking University, Health Science Center, Beijing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Guo
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Mao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Rongjing
authors.initials: R
authors.lastname: Song
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jia
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lei
authors.forename: David M
authors.initials: DM
authors.lastname: Irwin
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Huanran
authors.initials: H
authors.lastname: Tan
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000375:Aging / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D005508:Food Deprivation; D020869:Gene Expression Profiling; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D005941:Glucokinase / Q000172:deficiency* / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006579:Heterozygote; D006593:Hexokinase / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000235:genetics
chemical_list: D001786:Blood Glucose; D051273:Glucose Transporter Type 2; C495682:Slc2a2 protein, mouse; D005934:Glucagon; D006593:Hexokinase; D005941:Glucokinase; D011972:Receptor, Insulin; D005947:Glucose