{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:28:38Z","timestamp":1787610518905,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Liraglutide, an acylated analog of glucagon-like peptide 1 (GLP-1), could improve glycemic control in diabetes. Moreover, endogenous opioid peptides play a role in blood sugar regulation. Since GLP-1 receptors are also expressed in extra-pancreatic tissues, this study investigates the effect of liraglutide on endogenous opioid secretion in type 1-like diabetes. The endogenous opioid level was determined by enzyme-linked immunosorbent assay. The direct effect of liraglutide on endogenous opioid secretion was determined in the isolated adrenal medulla. Acute treatment with liraglutide dose-dependently attenuated hyperglycemia, and increased the plasma opioid neuropeptide, beta-endorphin (BER) levels in diabetic rats. These effects have been blocked by GLP-1 receptor antagonist, naloxone. Additionally, the effects of liraglutide were markedly reduced in adrenalectomized diabetic rats. In the isolated adrenal medulla, liraglutide induced BER secretion and increased the BER mRNA levels. Subcellular effects of liraglutide on the adrenal gland were further identified to mediate through the exchange proteins directly activated by cAMP, mainly using the pharmacological blockade. After repeatedly administering liraglutide, metabolic changes in diabetic rats were investigated, and genes associated with gluconeogenesis in the liver were downregulated. Naloxone pretreatment inhibited these effects of liraglutide, indicating the involvement of endogenous opioids. The present study indicated that liraglutide had an acute effect of reducing hyperglycemia by regulating endogenous opioid BER and modifying the glucose homeostasis.<\/jats:p>","DOI":"10.3390\/ph13110407","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T09:46:18Z","timestamp":1605865578000},"page":"407","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Liraglutide Activates Glucagon-Like Peptide 1 Receptor to Attenuate Hyperglycemia through Endogenous Beta-Endorphin in Diabetic Rats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4983-4666","authenticated-orcid":false,"given":"Kai-Chun","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Tajen University, Pingtung 907, Taiwan"},{"name":"Pharmacological Department of Herbal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan"},{"name":"Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nursing, Tzu Chi University of Science and Technology, Hualien City 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Chuen","family":"Shieh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Tajen University, Pingtung 907, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juei-Tang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Chi-Mei Medical Center, Tainan City 710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Gerontology and Health Care Management, Chang Gung University of Science and Technology, Taoyuan City 613, Taiwan"},{"name":"Department of Otorhinolaryngology, Taipei City Hospital, Taipei City 110, Taiwan"},{"name":"Department of Exercise and Health Sciences, University of Taipei, Taipei City 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1021\/jm9909645","article-title":"Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration","volume":"43","author":"Knudsen","year":"2000","journal-title":"J. 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