المؤلفون: Masatoshi Tanaka, Tomoko Tanaka, Daiji Kawanami, Takako Kawanami, Takashi Nomiyama, Shinichiro Irie, Ryoko Motonaga, Kazuki Nabeshima, Nobuya Hamanoue, Yuriko Hamaguchi, Makito Tanabe, Tsuyoshi Horikawa, Toru Shigeoka, Toshihiko Yanase

المصدر: Journal of Diabetes Investigation, Vol 11, Iss 5, Pp 1137-1149 (2020)
Journal of Diabetes Investigation

مصطلحات موضوعية: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Apoptosis, Mice, Prostate cancer, 0302 clinical medicine, Tumor Cells, Cultured, Medicine, Receptor, Aged, 80 and over, medicine.diagnostic_test, digestive, oral, and skin physiology, Articles, General Medicine, Middle Aged, Cell cycle, Prognosis, Gene Expression Regulation, Neoplastic, Real-time polymerase chain reaction, Original Article, Glucagon‐like peptide‐1 receptor, hormones, hormone substitutes, and hormone antagonists, Adult, Basic Science and Research, endocrine system, Mice, Nude, 030209 endocrinology & metabolism, Glucagon-Like Peptide-1 Receptor, Diseases of the endocrine glands. Clinical endocrinology, Flow cytometry, Young Adult, 03 medical and health sciences, In vivo, Biomarkers, Tumor, Internal Medicine, Animals, Humans, Aged, Cell Proliferation, business.industry, Cell growth, Prostatic Neoplasms, Cancer, medicine.disease, RC648-665, Xenograft Model Antitumor Assays, 030104 developmental biology, Cancer research, business

الوصف: Aims/Introduction Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti‐prostate cancer effect of glucagon‐like peptide‐1 receptor (GLP‐1R) agonist exendin‐4. The attenuation of cell proliferation in the prostate cancer cell line was dependent on GLP‐1R expression. Here, we examined the relationship between human prostate cancer severity and GLP‐1R expression, as well as the effect of forced expression of GLP‐1R using a lentiviral vector. Materials and Methods Prostate cancer tissues were extracted by prostatectomy and biopsy. GLP‐1R was overexpressed in ALVA‐41 cells using a lentiviral vector (ALVA‐41‐GLP‐1R cells). GLP‐1R expression was detected by immunohistochemistry and quantitative polymerase chain reaction. Cell proliferation was examined by growth curves and bromodeoxyuridine incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were carried out using a xenografted model. Results GLP‐1R expression levels were significantly inversely associated with the Gleason score of human prostate cancer tissues. Abundant GLP‐1R expression and functions were confirmed in ALVA‐41‐GLP‐1R cells. Exendin‐4 significantly decreased ALVA‐41‐GLP‐1R cell proliferation in a dose‐dependent manner. DNA synthesis and G1‐to‐S phase transition were inhibited in ALVA‐41‐GLP‐1R cells. SKP2 expression was decreased and p27Kip1 protein was subsequently increased in ALVA‐41‐GLP‐1R cells treated with exendin‐4. In vivo experiments carried out by implanting ALVA‐41‐GLP‐1R cells showed that exendin‐4 decreased prostate cancer growth by activation of GLP‐1R overexpressed in ALVA41‐GLP‐1R cells. Conclusions Forced expression of GLP‐1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progression in vitro and in vivo. Therefore, GLP‐1R activation might be a potential therapy for prostate cancer.
Forced expression of glucagon‐like peptide‐1 receptor attenuates prostate cancer cell proliferation by inhibiting cell cycle progression both in vitro and in vivo. Glucagon‐like peptide‐1 receptor activation might be a potential therapy for not only type 2 diabetes, but also prostate cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b206b93d5bd5e14e7fa0638780ac368Test
https://doaj.org/article/46b73efe4bc4460ab61d39d90ff1417dTest

المؤلفون: Yuichiro Yamada, Kenta Murotani, Yusuke Seino, Yutaka Seino, Minori Ishitobi, Yuji Yamazaki, Yuuka Fujiwara, Ryota Usui, Yoshiyuki Hamamoto, Hitoshi Kuwata, Sodai Kubota, Daisuke Yabe, Takeshi Kurose, Takuya Haraguchi, Saki Kubota-Okamoto

المصدر: Journal of Diabetes Investigation
Journal of Diabetes Investigation, Vol 12, Iss 12, Pp 2162-2171 (2021)

مصطلحات موضوعية: Blood Glucose, Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Glucagon-Like Peptides, Gastric emptying, Type 2 diabetes, chemistry.chemical_compound, 0302 clinical medicine, Japan, Insulin, Prospective Studies, digestive, oral, and skin physiology, Articles, General Medicine, Middle Aged, Postprandial Period, Clinical Science and Care, Postprandial, GLP‐1 receptor agonist, Female, Original Article, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, endocrine system, medicine.medical_specialty, Recombinant Fusion Proteins, 030209 endocrinology & metabolism, Gastric Inhibitory Polypeptide, Diseases of the endocrine glands. Clinical endocrinology, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Lixisenatide, Internal medicine, islet hormones, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Glucagon-like peptide 1 receptor, Liraglutide, business.industry, RC648-665, Glucagon, medicine.disease, Immunoglobulin Fc Fragments, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Dulaglutide, Apolipoprotein B-48, Peptides, business

الوصف: Aims/Introduction Differences in the glucose‐lowering mechanisms of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting. Materials and Methods A single‐arm, prospective, observational study was conducted to evaluate the effects of various GLP‐1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate. Participants were subjected to meal tolerance tests before and 2 weeks and 12 weeks after GLP‐1RA initiation. Effects on postprandial secretions of glucose‐dependent insulinotropic polypeptide (GIP) and apolipoprotein B48 were also investigated. Results Eighteen subjects with type 2 diabetes received one of three GLP‐1RAs, i.e., lixisenatide, n = 7; liraglutide, n = 6; or dulaglutide, n = 5. While 12‐week administration of all of the GLP‐1RAs significantly reduced HbA1c, only lixisenatide and liraglutide, but not dulaglutide, significantly reduced body weight. Postprandial glucose elevation was improved by all of the GLP‐1RAs. Postprandial insulin levels were suppressed by lixisenatide, while insulin levels were enhanced by liraglutide. Postprandial glucagon levels were suppressed by lixisenatide. The gastric emptying rate was significantly delayed by lixisenatide, while liraglutide and dulaglutide had limited effects on gastric emptying. GIP secretion was suppressed by lixisenatide and liraglutide. Apolipoprotein B48 secretion was suppressed by all of the GLP‐1RAs. Conclusions All of the GLP‐1RAs were found to improve HbA1c in a 12‐week prospective observational study in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose‐lowering effects and body weight reduction were observed.
GLP‐1 receptor agonists (lixisenatide, liraglutide, and dulaglutide) were found to improve postprandial glucose excursions in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose‐lowering effects were observed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::306175bf3a5c32c1eda622a58314861dTest
https://doi.org/10.1111/jdi.13598Test

المؤلفون: Kohei Kaku, Tomohiko Kimura

المصدر: Journal of Diabetes Investigation
Journal of Diabetes Investigation, Vol 12, Iss 7, Pp 1141-1143 (2021)

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, endocrine system, Endocrinology, Diabetes and Metabolism, Incretin, 030209 endocrinology & metabolism, Type 2 diabetes, JDI Updates, Incretins, Diseases of the endocrine glands. Clinical endocrinology, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Drug Development, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Intensive care medicine, Dipeptidyl-Peptidase IV Inhibitors, business.industry, digestive, oral, and skin physiology, General Medicine, RC648-665, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 2, business, hormones, hormone substitutes, and hormone antagonists

الوصف: This article is about new prospects for incretin-related drugs in the treatment of type 2 diabetes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09b35fc932a1083bf8b9daf34a5841fcTest
https://pubmed.ncbi.nlm.nih.gov/33151639Test

المؤلفون: Katsumi Iizuka, Daisuke Yabe, Sodai Kubota, Yangyang Liu

المصدر: Journal of Diabetes Investigation
Journal of Diabetes Investigation, Vol 11, Iss 6, Pp 1422-1425 (2020)

مصطلحات موضوعية: 0301 basic medicine, Cardiotonic Agents, Endocrinology, Diabetes and Metabolism, Metabolite, 030209 endocrinology & metabolism, Pharmacology, Diseases of the endocrine glands. Clinical endocrinology, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adenosine Triphosphate, Glucagon-Like Peptide 1, Commentaries, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Cyclic adenosine monophosphate, Protein kinase A, education, education.field_of_study, business.industry, Pinocytosis, General Medicine, Soluble adenylyl cyclase, RC648-665, Prognosis, Adenosine, Cytoprotection, Peptide Fragments, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Commentary, business, Adenosine triphosphate, medicine.drug, Signal Transduction

الوصف: Molecular mechanism underlying glucagon-like peptide-1 exertion of cardioprotective effects in glucagon-like peptide-1 receptor-dependent and -independent manners. Glucagon-like peptide-1 (28-36a) enters coronary artery endothelial cells through macropinocytosis and binds to mitochondrial trifunctional protein-α, shifting substrate utilization to increase adenosine triphosphate production and modulating a adenosine triphosphate-sensor soluble adenylyl cyclase, thereby producing cyclic adenosine monophosphate and activating protein kinase A to exert cytoprotection from oxidative injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f723c66d952b65d7b8b3a65732d680acTest
https://pubmed.ncbi.nlm.nih.gov/32428993Test

المؤلفون: David A. D'Alessio

المصدر: Journal of Diabetes Investigation

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, endocrine system, Proceedings of INCRETIN 2015, A Symposium Celebrating the 45th Anniversary of the Discovery of GIP, 29–31 July 2015, Vancouver, Canada. This publication has been supported by: The Local Organizing Committee of INCRETIN 2015, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Mini Review, Incretin, 030209 endocrinology & metabolism, Proglucagon, Incretins, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, Glucagon-Like Peptide 1, Internal medicine, Internal Medicine, medicine, Animals, Humans, Insulin, Review Articles, geography, geography.geographical_feature_category, business.industry, Insulin secretion, digestive, oral, and skin physiology, General Medicine, Fasting, Islet, Glucagon-like peptide-1, Glucagon‐like peptide‐1, 030104 developmental biology, Postprandial, Endocrinology, Glucagon-Secreting Cells, Blood sugar regulation, business, hormones, hormone substitutes, and hormone antagonists, Hormone

الوصف: Glucagon‐like peptide‐1 (GLP‐1) is a product of proglucagon cleavage synthesized in L cells in the intestinal mucosa, α‐cells in the pancreatic islet, and neurons in the nucleus of the solitary tract. GLP‐1 is essential for normal glucose tolerance and acts through a specific GLP‐1 receptor that is expressed by islet β‐cells as well as other cell types. Because plasma concentrations of GLP‐1 increase following meal ingestion it has been generally presumed that GLP‐1 acts as a hormone, communicating information from the intestine to the endocrine pancreas through the circulation. However, there are a number of problems with this model including low circulating concentrations of GLP‐1 in plasma, limited changes after meal ingestion and rapid metabolism in the plasma. Moreover, antagonism of systemic GLP‐1 action impairs insulin secretion in the fasting state, suggesting that the GLP‐1r is active even when plasma GLP‐1 levels are low and unchanging. Consistent with these observations, deletion of the GLP‐1r from islet β‐cells causes intolerance after IP or IV glucose, challenges that do not induce GLP‐1 secretion. Taken together, these data support a model whereby GLP‐1 acts through neural or paracrine mechanisms to regulate physiologic insulin secretion. In contrast, bariatric surgery seems to be a condition in which circulating GLP‐1 could have an endocrine effect. Both gastric bypass and sleeve gastrectomy are associated with substantial increases in postprandial GLP‐1 release and in these conditions interference with GLP‐1r signaling has a significant impact on glucose regulation after eating. Thus, with either bariatric surgery or treatment with long‐acting GLP‐1r agonists, circulating peptide mediates insulinotropic activity. Overall, a case can be made that physiologic actions of GLP‐1 are not hormonal, but that an endocrine mechanism of GLP‐1r activation can be co‐opted for therapeutics.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::06b7024e1ac004df6533654433dfddf5Test
http://europepmc.org/articles/PMC4854505Test

المؤلفون: Kenichi Katsurada, Toshihiko Yada

المصدر: Journal of Diabetes Investigation

مصطلحات موضوعية: 0301 basic medicine, Agonist, medicine.medical_specialty, endocrine system, medicine.drug_class, Proceedings of INCRETIN 2015, A Symposium Celebrating the 45th Anniversary of the Discovery of GIP, 29–31 July 2015, Vancouver, Canada. This publication has been supported by: The Local Organizing Committee of INCRETIN 2015, Endocrinology, Diabetes and Metabolism, Mini Review, Enteroendocrine Cells, Central nervous system, Incretin, Enteroendocrine cell, Biology, Cardiovascular, Brain stem, Glucagon-Like Peptide-1 Receptor, Cardiovascular Physiological Phenomena, 03 medical and health sciences, chemistry.chemical_compound, Mice, Glucagon-Like Peptide 1, Internal medicine, Internal Medicine, medicine, Solitary Nucleus, Animals, Humans, Neurotransmitter, Receptor, Review Articles, Solitary nucleus, Feeding, digestive, oral, and skin physiology, General Medicine, Feeding Behavior, Glucagon-like peptide-1, Rats, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, hormones, hormone substitutes, and hormone antagonists

الوصف: Glucagon‐like peptide‐1 (GLP‐1) is derived from both the enteroendocrine L cells and preproglucagon‐expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP‐1 is cleaved by dipeptidyl peptidase‐4 yielding a half‐life of less than 2 min, it is plausible that the gut‐derived GLP‐1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP‐1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain‐derived GLP‐1 is restriction of feeding. GLP‐1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP‐1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase‐4, and is highly likely to act on the brain by passing through the blood–brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP‐1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP‐1 and the pathway by which peripheral GLP‐1 informs the brain, and then discuss recent findings on the central effects of GLP‐1 and GLP‐1 receptor agonists.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdddc2c0f0749b93528dfada6f8fc391Test
http://europepmc.org/articles/PMC4854507Test

المؤلفون: Jacob Hecksher-Sørensen, Charles Pyke, Anna Secher, Lotte Bjerre Knudsen

المصدر: Journal of Diabetes Investigation

مصطلحات موضوعية: 0301 basic medicine, Agonist, endocrine system, medicine.medical_specialty, Pro-Opiomelanocortin, medicine.drug_class, Proceedings of INCRETIN 2015, A Symposium Celebrating the 45th Anniversary of the Discovery of GIP, 29–31 July 2015, Vancouver, Canada. This publication has been supported by: The Local Organizing Committee of INCRETIN 2015, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Mini Review, Hypothalamus, Neuropeptide, 030209 endocrinology & metabolism, Nerve Tissue Proteins, Pharmacology, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Animals, Humans, Obesity, Amphetamine, Pancreas, Review Articles, media_common, Neurons, Gastric emptying, Liraglutide, business.industry, digestive, oral, and skin physiology, Brain, Appetite, General Medicine, Glucagon-like peptide-1, Arcuate nucleus, 030104 developmental biology, Endocrinology, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug

الوصف: Liraglutide is a glucagon‐like peptide‐1 receptor (GLP‐1R) agonist marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide reduces bodyweight, and has recently also been approved for the obesity indication. Acutely, GLP‐1 markedly reduces gastric emptying, and this effect was previously believed to at least partly explain the effect on bodyweight loss. However, recent studies in both humans and animals have shown that GLP‐1R agonists, such as liraglutide, that lead to pharmacological concentrations for 24 h/day only have a minor effect on gastric emptying; such an effect is unlikely to have lasting effects on appetite reduction. Liraglutide has been shown to have direct effects in the arcuate nucleus of the rodent brain, activating pro‐opiomelanocortin neurons and increasing levels of the cocaine‐ and amphetamine‐stimulated transcript neuropeptide messenger ribonucleic acid, which correlate nicely to clinical studies where liraglutide was shown to increase feelings of satiety. However, despite the lack of a GLP‐1R on agouti‐related peptide/neuropeptide Y neurons, liraglutide also was able to prevent a hunger associated increase in agouti‐related peptide and neuropeptide Y neuropeptide messenger ribonucleic acid, again with a strong correlation to clinical studies that document reduced hunger feelings in patients while taking liraglutide. Studies using fluorescent labeled liraglutide, as well as other GLP‐1R agonists, and analysis using single‐plane illumination microscopy show that such medium‐sized peptide‐based compounds can directly access not only circumventricular organs of the brain, but also directly access discrete regions in the hypothalamus. The direct effects of long‐acting GLP‐1R agonists in the hypothalamus are likely to be an important new pathway in understanding GLP‐1R agonist mediated weight loss.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc17fa3d1b418b194c82d67a0dfcb83fTest
https://pubmed.ncbi.nlm.nih.gov/27186357Test