Format

Send to

Choose Destination
See comment in PubMed Commons below
Regul Pept. 2011 Apr 11;167(2-3):177-84. doi: 10.1016/j.regpep.2011.01.003. Epub 2011 Jan 21.

GLP-1-derived nonapeptide GLP-1(28-36)amide targets to mitochondria and suppresses glucose production and oxidative stress in isolated mouse hepatocytes.

Author information

1
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA 02114, United States.

Abstract

BACKGROUND:

Uncontrolled hepatic glucose production (gluconeogenesis), and glycogenolysis, is a major contributor to the fasting hyperglycemia associated with type 2 diabetes. Here we report the discovery of a C-terminal nonapeptide (FIAWLVKGRamide) derived from GLP-1 that suppresses glucose production and oxidative stress in isolated mouse hepatocytes. The nonapeptide, GLP-1(28-36)amide, was reported earlier to be a major product derived from the cleavage of GLP-1 by the endopeptidase NEP 24.11.

METHODS AND RESULTS:

Hepatocytes were isolated from the livers of normal and diet-induced obese mice. We find that the GLP-1(28-36)amide nonapeptide rapidly enters isolated mouse hepatocytes by GLP-1 receptor-independent mechanisms, and targets to mitochondria where it inhibits gluconeogenesis and oxidative stress.

CONCLUSIONS:

These findings suggest that GLP-1 not only acts on a cell surface G-protein coupled receptor activating kinase-regulated signaling pathways, but a small C-terminal peptide derived from GLP-1 also enters cells, targets mitochondria, and exerts insulin-like actions by modulating oxidative phosphorylation. GLP-1(28-36)amide, or a peptide mimetic derived there from, might prove to be a useful treatment for fasting hyperglycemia and metabolic syndrome in type 2 diabetes.

PMID:
21256872
DOI:
10.1016/j.regpep.2011.01.003
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center