Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis.
Type 2 diabetes mellitus (T2DM) is rapidly prevailing as a serious global health problem. Current treatments for T2DM may cause side effects, thus highlighting the need for newer and safer therapies. We tested the hypothesis that dietary capsaicin regulates glucose homeostasis through the activation of transient receptor potential vanilloid 1 (TRPV1)-mediated glucagon-like peptide-1 (GLP-1) secretion in the intestinal cells and tissues. Wild-type (WT) and TRPV1 knockout (TRPV1(-/-)) mice were fed dietary capsaicin for 24 weeks. TRPV1 was localized in secretin tumor cell-1 (STC-1) cells and ileum. Capsaicin stimulated GLP-1 secretion from STC-1 cells in a calcium-dependent manner through TRPV1 activation. Acute capsaicin administration by gastric gavage increased GLP-1 and insulin secretion in vivo in WT but not in TRPV1(-/-) mice. Furthermore, chronic dietary capsaicin not only improved glucose tolerance and increased insulin levels but also lowered daily blood glucose profiles and increased plasma GLP-1 levels in WT mice. However, this effect was absent in TRPV1(-/-) mice. In db/db mice, TRPV1 activation by dietary capsaicin ameliorated abnormal glucose homeostasis and increased GLP-1 levels in the plasma and ileum. The present findings suggest that TRPV1 activation-stimulated GLP-1 secretion could be a promising approach for the intervention of diabetes.
Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China.
Peijian
P
Wang
Zhencheng
Z
Yan
Jian
J
Zhong
Jing
J
Chen
Yinxing
Y
Ni
Li
L
Li
Liqun
L
Ma
Zhigang
Z
Zhao
Daoyan
D
Liu
Zhiming
Z
Zhu
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D019858:Enteroendocrine Cells / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007082:Ileum / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D050916:TRPV Cation Channels / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D052216:Glucagon-Like Peptide 1; D002211:Capsaicin