Leptin therapy in insulin-deficient type I diabetes.
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.
Wang
May-yun
MY
Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Chen
Lijun
L
Clark
Gregory O
GO
Lee
Young
Y
Stevens
Robert D
RD
Ilkayeva
Olga R
OR
Wenner
Brett R
BR
Bain
James R
JR
Charron
Maureen J
MJ
Newgard
Christopher B
CB
Unger
Roger H
RH
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
D001786:Blood Glucose; D004343:Drug Implants; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014280:Triglycerides; D005934:Glucagon; D000263:Adenylate Kinase