Identification of Genipin as a Potential Treatment for Type 2 Diabetes.
Int J Mol Sci
; 24(3)2023 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-36768454
ABSTRACT
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 ß-cells. While there are several pharmaceutical therapies for T2D, no effective treatment is available for reversing the functional decline of pancreatic ß-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 ß-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 Ca2+. Inhibition of PLC ablated genipin-stimulated Ca2+ increase and GLP-1 secretion, suggesting that genipin-induced GLP-1 release from cells is dependent on the PLC/Ca2+ 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.
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Diabetes Mellitus Tipo 2
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article