Production of a mouse strain with impaired glucose tolerance by systemic
heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes
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Authors: | Mikako SAITO Asako KANEDA Tae SUGIYAMA Ryousuke IIDA Keiko OTOKUNI Misako KABURAGI Hideaki MATSUOKA |
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Affiliation: | Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan |
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Abstract: | Exon II of glucokinase (Gk) was deleted to produce a systemicheterozygous Gk knockout (Gk+/−) mouse. Therelative expression levels of Gk in the heart, lung, liver, stomach, andpancreas in Gk+/− mice ranged from 0.41–0.68 versus that inwild (Gk+/+) mice. On the other hand, its expression levels inthe brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels inthe spleen and kidney were nearly zero. Gk knockout caused no remarkableoff-target effect on the expression of 7 diabetes causing genes (Shp,Hnf1a, Hnf1b, Irs1,Irs2, Kir6.2, and Pdx1) in 10 organs.The glucose tolerance test was conducted to determine the blood glucose concentrationsjust after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). TheFBG-GTT2h plots obtained with the wild strain fed the control diet (CD),Gk+/− strain fed the CD, andGk+/− strain fed the HFD were distributed in separate areasin the FBG-GTT2h diagram. The respective areas could be defined as the normal state,prediabetes state, and diabetes state, respectively. Based on the results, the criteriafor prediabetes could be defined for the Gk+/− straindeveloped in this study. |
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Keywords: | glucokinase glucose tolerance test high-fat diet prediabetes model mouse systemic heterozygous knockout |
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