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Identification of Genipin as a Potential Treatment for Type 2 Diabetes
The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of β-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the funct...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917294/ https://www.ncbi.nlm.nih.gov/pubmed/36768454 http://dx.doi.org/10.3390/ijms24032131 |
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author | Wu, Yajun Wang, Yao Liu, Dongmin |
author_facet | Wu, Yajun Wang, Yao Liu, Dongmin |
author_sort | Wu, Yajun |
collection | PubMed |
description | The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of β-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic β-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca(2+). Inhibition of PLC ablated genipin-stimulated Ca(2+) increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca(2+) pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg/kg/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease. |
format | Online Article Text |
id | pubmed-9917294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99172942023-02-11 Identification of Genipin as a Potential Treatment for Type 2 Diabetes Wu, Yajun Wang, Yao Liu, Dongmin Int J Mol Sci Article The prevalence of type 2 diabetes (T2D) has been rising dramatically in many countries around the world. The main signatures of T2D are insulin resistance and dysfunction of β-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic β-cells in T2D patients. It has been well recognized that glucagon-like peptide-1 (GLP-1), which is an incretin hormone secreted from intestinal L-cells, plays a vital role in regulating glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell function. We found that genipin, a natural compound from Elli, can directly target intestinal L-cells, leading to the secretion of GLP-1. Incubation of the cells with genipin elicited a rapid increase in intracellular Ca(2+). Inhibition of PLC ablated genipin-stimulated Ca(2+) increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca(2+) pathway. In vivo, acute administration of genipin stimulated GLP-1 secretion in mice. Chronically, treatment with genipin via oral gavage at 50 mg/kg/day for 6 weeks reversed hyperglycemia and insulin resistance in high-fat-diet (HFD)-induced obese mice. Moreover, genipin alleviated the impaired lipid metabolism and decreased lipid accumulation in the liver of obese mice. These results suggest that naturally occurring genipin might potentially be a novel agent for the treatment of T2D and diet-induced fatty liver disease. MDPI 2023-01-21 /pmc/articles/PMC9917294/ /pubmed/36768454 http://dx.doi.org/10.3390/ijms24032131 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Yajun Wang, Yao Liu, Dongmin Identification of Genipin as a Potential Treatment for Type 2 Diabetes |
title | Identification of Genipin as a Potential Treatment for Type 2 Diabetes |
title_full | Identification of Genipin as a Potential Treatment for Type 2 Diabetes |
title_fullStr | Identification of Genipin as a Potential Treatment for Type 2 Diabetes |
title_full_unstemmed | Identification of Genipin as a Potential Treatment for Type 2 Diabetes |
title_short | Identification of Genipin as a Potential Treatment for Type 2 Diabetes |
title_sort | identification of genipin as a potential treatment for type 2 diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917294/ https://www.ncbi.nlm.nih.gov/pubmed/36768454 http://dx.doi.org/10.3390/ijms24032131 |
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