Adiponectin increases secretion of rat submandibular gland via adiponectin receptors-mediated AMPK signaling

• Published in: PloS one 2013-05, Vol.8 (5), p.e63878-e63878
• Main Authors: Ding, Chong, Li, Li, Su, Yun-Chao, Xiang, Ruo-Lan, Cong, Xin, Yu, Hong-Kui, Li, Sheng-Lin, Wu, Li-Ling, Yu, Guang-Yan
• Format: Article
• Language: English
• Subjects: Acinar cells; Adenosine kinase; Adenosine monophosphate; Adenylate Kinase - metabolism; Adiponectin; Adiponectin - pharmacology; AMP; Animals; Aquaporin 5 - metabolism; Biology; Cardiovascular disease; Cell Line; Cytoplasm; Diabetes; Education; Electric Impedance; Electrical junctions; Energy metabolism; Enzyme Activation - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Exocrine glands; Glands; Hospitals; Humans; Immunofluorescence; Immunoglobulins; In Vitro Techniques; Inflammation; Kinases; Laboratory animals; Male; Maxillofacial surgery; Medicine; Metabolism; mRNA; Perfusion; Permeability; Phosphorylation - drug effects; Physiology; Polymerase chain reaction; Protein kinase; Protein kinases; Protein Transport - drug effects; Proteins; Rats; Rats, Sprague-Dawley; Receptors; Receptors, Adiponectin - metabolism; Ribonucleic acid; RNA; RNA, Small Interfering - metabolism; RNA-mediated interference; Rodents; Saliva; Science; Signal Transduction - drug effects; Signaling; Submandibular gland; Submandibular Gland - cytology; Submandibular Gland - enzymology; Submandibular Gland - secretion; Submandibular Gland - ultrastructure; Tight junctions; Tight Junctions - drug effects; Tight Junctions - metabolism; Tight Junctions - ultrastructure; Tissues; Type 2 diabetes; Ultrastructure
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063878

Adiponectin and adiponectin receptors (AdipoR1/2) are expressed in various tissues and are involved in the regulation of multiple functions such as energy metabolism and inflammatory responses. However, the effect of adiponectin and AdipoRs in submandibular glands has not been fully evaluated. In the present study, we found that mRNA and protein of both adiponectin and AdipoR1/2 were expressed in rat submandibular glands and in the SMG-C6 cell line, as evidenced by RT-PCR and Western blot analysis. Immunofluorescence staining showed that adiponectin was diffused in the cytoplasm, while AdipoR1/2 was concentrated in the membrane of acinar cells. Saliva flow was significantly increased by full length adiponectin (fAd) or globular adiponectin (gAd) perfusion in isolated rat submandibular glands. 5-Aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR), an adenosine monophosphate activated protein kinase (AMPK) activator, also increased saliva secretion. fAd, gAd, and AICAR all increased the average width of apical tight junctions in perfused submandibular glands, and decreased transepithelial electrical resistance (TER) in SMG-C6 cells, suggesting that adiponectin promoted secretion by modulating paracellular permeability. fAd and gAd increased p-AMPK levels, while AraA, an AMPK antagonist, abolished fAd- and gAd-induced changes in secretion, tight junction ultrastructure, and TER. Moreover, both AdipoR1 and AdipoR2 were required for fAd- or gAd-induced p-AMPK and TER responses, suggesting from their inhibition following AdipoR1 or AdipoR2 knockdown, and co-knockdown of AdipoRs by RNA interference. Our results suggest that adiponectin functions as a promoter of salivary secretion in rat submandibular glands via activation of AdipoRs, AMPK, and paracellular permeability.