title: Repin1 deficiency improves insulin sensitivity and glucose metabolism in db/db mice by reducing adipose tissue mass and inflammation.
abstract: Replication initiator 1 (Repin1) is a zinc finger protein playing a role in insulin sensitivity, body fat mass and lipid metabolism by regulating the expression key genes of glucose and lipid metabolism. Here, we tested the hypothesis that introgression of a Repin1 deletion into db/db mice improves glucose metabolism in vivo. We generated a whole body Repin1 deficient db/db double knockout mouse (Rep1(-/-)x db/db) and systematically characterized the consequences of Repin1 deficiency on insulin sensitivity, glucose and lipid metabolism parameters and fat mass. Hyperinsulinemic-euglycemic clamp studies revealed significantly improved insulin sensitivity in Rep1(-/-)x db/db mice, which are also characterized by lower HbA1c, lower body fat mass and reduced adipose tissue (AT) inflammation area. Our study provides evidence that loss of Repin1 in db/db mice improves insulin sensitivity and reduces chronic hyperglycemia most likely by reducing fat mass and AT inflammation.
authors.affiliation: German Diabetes Center Leipzig, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kunath
authors.affiliation: Department of Medicine, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Hesselbarth
authors.affiliation: Institute of Anatomy, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
authors.affiliation: German Diabetes Center Leipzig, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kern
authors.affiliation: IFB AdiposityDiseases, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dommel
authors.affiliation: IFB AdiposityDiseases, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: German Diabetes Center Leipzig, University of Leipzig, 04103, Leipzig, Germany; Department of Medicine, University of Leipzig, 04103, Leipzig, Germany; IFB AdiposityDiseases, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: German Diabetes Center Leipzig, University of Leipzig, 04103, Leipzig, Germany; Department of Medicine, University of Leipzig, 04103, Leipzig, Germany; IFB AdiposityDiseases, University of Leipzig, 04103, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: IFB AdiposityDiseases, University of Leipzig, 04103, Leipzig, Germany. Electronic address: nora.kloeting@medizin.uni-leipzig.de.
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D050154:Adiposity; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051379:Mice; D018345:Mice, Knockout; D016601:RNA-Binding Proteins
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; D016601:RNA-Binding Proteins; C552723:Repin1 protein, mouse; D005947:Glucose
keywords: Crown like structure; Db/db, adipose tissue; Dyslipidemia; Hypertriglyceridemia; Insulin sensitivity; Obesity; Repin1; Rip60