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Series GSE48815 Query DataSets for GSE48815
Status Public on Apr 01, 2014
Title Glucagon regulates Hepatic Kisspeptin1 to Impair Insulin Secretion in Diabetes Mellitus
Organism Mus musculus
Experiment type Expression profiling by array
Summary Glucagon and insulin are counter-regulatory pancreatic hormones that precisely control blood glucose homeostasis1. Type 2 diabetes mellitus (T2DM) is characterized by inappropriately elevated blood glucagon2-5 levels as well as insufficient glucose stimulated insulin secretion (GSIS) by pancreatic ß-cells6. Early in the pathogenesis of T2DM, hyperglucagonemia is observable antecedent to ß-cell dysfunction7-9; and in mice, liver-specific activation of glucagon receptor-dependent signaling results in impaired GSIS10. However, the mechanistic relationship between hyperglucagonemia, hepatic glucagon action, and ß-cell dysfunction remains poorly understood. Here we show that glucagon action stimulates hepatic production of the neuropeptide kisspeptin1, which acts in an endocrine manner on ß-cells to suppress GSIS. In vivo glucagon administration acutely stimulates hepatic kisspeptin1 production, and kisspeptin1 is increased in livers from humans with T2DM and from mouse models of diabetes mellitus. Synthetic kisspeptin1 potently suppresses GSIS in vivo and in vitro from normal isolated islets, which express the kisspeptin1 receptor Kiss1R. Administration of a Kiss1R antagonist in diabetic Leprdb/db mice potently augments GSIS and reduces glycemia. Our observations indicate in the pathogenesis of T2DM an endocrine mechanism sequentially linking hyperglucagonemia via hepatic kisspeptin1 production to impaired insulin secretion. In addition, our findings suggest Kiss1R antagonism as a therapeutic avenue to improve ß-cell function in T2DM.
Overall design Total RNA from L-Δprkar1a KO mice compared to control D-glucose mice
Contributor(s) Song W, Turner SD, Hussain MA
Citation(s) 24703698
Submission date Jul 11, 2013
Last update date Jun 14, 2018
Contact name Stephen Turner
Organization name Signature Science, LLC
Street address 1670 Discovery Drive
City Charlottesville
State/province VA
ZIP/Postal code 22911
Country USA
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (15)
GSM1185206 Liver ctrl rep1
GSM1185207 Liver PRKAR1A ko rep1
GSM1185208 Liver ctrl rep2
BioProject PRJNA211832

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Supplementary file Size Download File type/resource
GSE48815_RAW.tar 3.1 Mb (http)(custom) TAR
GSE48815_non-normalized.txt.gz 6.0 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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