Adiponectin Increases Secretion of Rat Submandibular Gland via Adiponectin Receptors-Mediated AMPK Signaling

Abstract

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.

Decreased submandibular adiponectin is involved in the progression of autoimmune sialoadenitis in non‐obese diabetic mice

“…In addition, AdipoR1/2 mRNA has been detected in cultured human minor salivary gland epithelial cells (Katsiougiannis et al , ) and mouse embryos SMG (Zhou et al , ). Our recent study has shown that adiponectin and AdipoRs are expressed in rat SMG (Ding et al , ). In the present study, we provided further evidence that adiponectin and AdipoRs were expressed in both mouse and human SMGs.…”

“…It is known that submandibular gland (SMG), which is structurally and functionally different from minor salivary gland, is the main resource of saliva under resting state (Langdon, ). Our laboratory recently found that adiponectin was expressed in rat SMG and adiponectin acted as a promoter of saliva secretion in isolated SMG (Ding et al , ). However, the possible role of adiponectin in SMG under pathological state is still unclear.…”

Measurement of salivary adiponectin concentrations in dogs

“…This suggests the presence of mild chronic gingival inflammation before tooth‐cleaning, which had resolved by day 14, and is similar to the changes described in people . Mechanisms involved in increased salivary adiponectin concentrations in the presence of chronic gingivitis would include (1) increased permeability of regional blood vessels due to localized periodontitis or gingivitis, leading to adiponectin leakage from the blood, or (2) increased local production of salivary adiponectin from a damaged gingiva, as a reaction of regulating local inflammation . Further studies should now be considered to elucidate the pathogenesis of increased salivary adiponectin in dogs with acute gingival inflammation.…”

Altered autophagy and sympathetic innervation in salivary glands from high-fat diet mice

“…Ding et al (2013) 10 described perfusion of isolated salivary glands with adiponectin which stimulated saliva secretion. Therefore we investigated if a high fat diet could modify the levels of adiponectin in submandibular gland.…”

“…8,9 Thus receptors present in salivary glands might be involved in the effects of metabolic changes regulation such as local inflammatory and immunological processes. 10 The consumption of high caloric palatable foods has increased significantly in recent decades leading obesity to achieve epidemic proportions with negative impacts for the economy and general health worldwide. 11,12 Therefore understanding the pathophysiology mechanism involved in the development of obesity and its related diseases has become timely.…”