AIM: Glucagon-like peptide-1 (GLP-1) produces pleiotropic effects binding to the GLP-1 receptor (GLP1-R), potentiating insulin secretion in the pancreas. GLP1-R is expressed in peripheral tissues and evidence for its role in reproduction has come from knockout mice, although the relationship between GLP-1 and male fertility needs to be clarified. Given that human sperm is an insulin-sensitive and insulin-secreting cell, we hypothesized that the GLP-1/GLP1-R axis may be expressed and functional in these cells. RESULTS AND DISCUSSION: We revealed the presence of GLP1-R by Western blotting and immunofluorescence analyses. Because Exendin-4 (Ex-4) displays similar functional properties to native GLP-1, we used this agonist to perform a dose-response study on progressive motility and cholesterol efflux, showing that 300 pM Ex-4 was the most effective treatment. These actions are mediated by GLP1-R and independent from sperm-secreted insulin. The exposure to Ex-4 fueled phosphatidylinositol-3-kinase (PI3K)/AKT signaling and was reversed by H89, indicating a protein kinase A (PKA)-dependence of GLP-1/GLP1-R signaling. It emerged that in sperm, insulin secretion regulated by Ex-4 did not occur in a strictly glucose-dependent manner. A stimulatory action of Ex-4/GLP1-R on lactate dehydrogenase and glucose-6-phosphate dehydrogenase (G6PDH) activities was observed. Ex-4/GLP1-R decreased triglycerides content concomitantly to enhanced lipase and acyl-coenzyme A (acyl-CoA) dehydrogenase activities, addressing a lipolytic effect. CONCLUSION: Collectively, we discovered that human sperm is a new GLP1 incretin target, broadening our knowledge about the effects of the GLP1-R agonist in the male reproductive field. Further findings in humans should be conducted in the future to confirm it and to improve the translational aspect of this study. Published by Oxford University Press on behalf of the Endocrine Society 2020.
AIM: Glucagon-like peptide-1 (GLP-1) produces pleiotropic effects binding to the GLP-1 receptor (GLP1-R), potentiating insulin secretion in the pancreas. GLP1-R is expressed in peripheral tissues and evidence for its role in reproduction has come from knockout mice, although the relationship between GLP-1 and male fertility needs to be clarified. Given that human sperm is an insulin-sensitive and insulin-secreting cell, we hypothesized that the GLP-1/GLP1-R axis may be expressed and functional in these cells. RESULTS AND DISCUSSION: We revealed the presence of GLP1-R by Western blotting and immunofluorescence analyses. Because Exendin-4 (Ex-4) displays similar functional properties to native GLP-1, we used this agonist to perform a dose-response study on progressive motility and cholesterol efflux, showing that 300 pM Ex-4 was the most effective treatment. These actions are mediated by GLP1-R and independent from sperm-secreted insulin. The exposure to Ex-4 fueled phosphatidylinositol-3-kinase (PI3K)/AKT signaling and was reversed by H89, indicating a protein kinase A (PKA)-dependence of GLP-1/GLP1-R signaling. It emerged that in sperm, insulin secretion regulated by Ex-4 did not occur in a strictly glucose-dependent manner. A stimulatory action of Ex-4/GLP1-R on lactate dehydrogenase and glucose-6-phosphate dehydrogenase (G6PDH) activities was observed. Ex-4/GLP1-R decreased triglycerides content concomitantly to enhanced lipase and acyl-coenzyme A (acyl-CoA) dehydrogenase activities, addressing a lipolytic effect. CONCLUSION: Collectively, we discovered that human sperm is a new GLP1 incretin target, broadening our knowledge about the effects of the GLP1-R agonist in the male reproductive field. Further findings in humans should be conducted in the future to confirm it and to improve the translational aspect of this study. Published by Oxford University Press on behalf of the Endocrine Society 2020.
Entities:
Keywords:
GLP1; GLP1-R; human ejaculated spermatozoa; male fertility
Authors: Cristina Antinozzi; Marco Lista; Luisa Caponecchia; Pietro Salacone; Carlo Minganti; Francesco A Battaglia; Luigi Di Luigi; Paolo Sgrò Journal: Front Endocrinol (Lausanne) Date: 2021-07-28 Impact factor: 5.555
Authors: Rossella Cannarella; Aldo E Calogero; Rosita A Condorelli; Emanuela A Greco; Antonio Aversa; Sandro La Vignera Journal: Andrology Date: 2021-05-05 Impact factor: 3.842