title: Leptin therapy in insulin-deficient type I diabetes.
abstract: In nonobese diabetic mice with uncontrolled type 1 diabetes, leptin therapy alone or combined with low-dose insulin reverses the catabolic state through suppression of hyperglucagonemia. Additionally, it mimics the anabolic actions of insulin monotherapy and normalizes hemoglobin A1c with far less glucose variability. We show that leptin therapy, like insulin, normalizes the levels of a wide array of hepatic intermediary metabolites in multiple chemical classes, including acylcarnitines, organic acids (tricarboxylic acid cycle intermediates), amino acids, and acyl CoAs. In contrast to insulin monotherapy, however, leptin lowers both lipogenic and cholesterologenic transcription factors and enzymes and reduces plasma and tissue lipids. The results imply that leptin administration may have multiple short- and long-term advantages over insulin monotherapy for type 1 diabetes.
authors.affiliation: Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: May-yun
authors.initials: MY
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.forename: Gregory O
authors.initials: GO
authors.lastname: Clark
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Olga R
authors.initials: OR
authors.lastname: Ilkayeva
authors.forename: Brett R
authors.initials: BR
authors.lastname: Wenner
authors.forename: James R
authors.initials: JR
authors.lastname: Bain
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Roger H
authors.initials: RH
authors.lastname: Unger
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004343:Drug Implants; D005786:Gene Expression Regulation; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use; D020738:Leptin / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000201:enzymology; D055442:Metabolome; D051379:Mice; D016688:Mice, Inbred NOD; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D004343:Drug Implants; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014280:Triglycerides; D005934:Glucagon; D000263:Adenylate Kinase