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Intercellular gap junctional communication is required for an optimal metabolic response of the functional units of liver
Author(s) -
Saez J C
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510250348
Subject(s) - gap junction , connexin 32 , connexin , biology , intracellular , stimulation , microbiology and biotechnology , neuromuscular junction , schwann cell , wild type , endocrinology , medicine , gene , neuroscience , genetics , mutant
The gap junction protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann's cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination in the mouse genome and have generated homozygous connexin32‐deficient mice that were viable and fertile but weighed on the average approximately ≈17% less than wild‐type controls. Electrical stimulation of sympathetic nerve in connexin32‐deficient liver triggered a 78% lower amount of glucose mobilization from glucose stores, when compared with wild‐type liver. Thus, connexin32‐containing gap junctions are essential in mouse liver for maximal intercellular propagation of the noradrenaline signal from sympathetic nerve endings, to perivenous (downstream) hepatocytes. In connexin32‐defective liver, the amount of connexin26 protein expressed was found to be lower than in wild‐type liver and the total area of gap junction plaques was approximately ≈1,000‐fold smaller than in wild‐type liver. In contrast to patients with connexin32 defects suffering from X chromosome‐linked Charcot‐Marie‐Tooth disease (CMTX) due to demyelination in Schwann cells of peripheral nerves, connexin32‐deficient mice did not show neurological abnormalities when analyzed at 3 months of age. It is possible, however, that they may develop neurodegenerative symptoms at an older age.