Dietary Bioactive Ingredients Modulating the cAMP Signaling in Diabetes Treatment

Wang, Yanan; Liu, Qing; Kang, Seong‐Gook; Huang, Kunlun; Tong, Teng

doi:10.3390/nu13093038

Cited by 7 publications

(4 citation statements)

References 125 publications

(148 reference statements)

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“…In addition to the colon and kidney, our results also indicated that olfr78 is widely distributed in the subcutaneous tissue, soleus, brown adipose tissue, liver, and pancreas (Figure 3a), which are also involved in the regulation of glucose homeostasis (Stanford et al, 2015;Wang et al, 2021;Wen et al, 2022). Recent studies have shown that some…”

Section: Discussionsupporting

confidence: 55%

Olfr78, a novel short‐chain fatty acid receptor, regulates glucose homeostasis and gut GLP‐1 secretion in mice

Wang,

Li,

Guo

et al. 2023

Food Frontiers

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Olfr78, which is a novel receptor for short‐chain fatty acid (SCFA) acetate and propionate, plays essential roles in some cellular processes. The present study aimed to investigate the role of olfr78 in regulating energy metabolism and delineate the underlying mechanisms using olfr78−/− mice. Deletion of olfr78 did not influence the adiposity of mice fed either normal chow or a high‐fat diet (HFD). However, olfr78−/− mice exhibited glucometabolic dysfunction, as evidenced by increased fasting blood glucose levels, decreased serum insulin levels, and impaired oral glucose tolerance under HFD feeding. When compared to wild‐type (WT) mice, olfr78 deficiency enhanced HFD‐induced gluconeogenesis and increased the mRNA expression of key gluconeogenic genes in the liver and kidney. Quantitative real‐time PCR results revealed that olfr78 expression was higher in the colon compared with other tissues in WT mice. Analysis of the gut microbiota in the feces of olfr78−/− mice using 16S rRNA gene sequencing revealed altered relative abundances of some representative SCFAs producers along with decreased levels of SCFAs, including propionic, isobutyric, 2‐methylbutyric, valeric, isovaleric, and 4‐methylvaleric acids. Importantly, mice lacking olfr78 had low circulating levels of glucagon‐like peptide 1 (GLP‐1). In the STC‐1 enteroendocrine cell line, propionate and acetate induced the secretion of the gut hormone GLP‐1, and this effect was partially abolished by olfr78 siRNA‐mediated knockdown. Together, these results suggest a previously undescribed, specific regulatory role for gut olfr78 in glucose homeostasis and highlight olfr78 as a potential target for diabetes treatment.

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Section: Discussionsupporting

confidence: 55%

Olfr78, a novel short‐chain fatty acid receptor, regulates glucose homeostasis and gut GLP‐1 secretion in mice

Wang,

Li,

Guo

et al. 2023

Food Frontiers

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“…At the same time, KEGG analysis identified novel pathways that are differentially regulated in diabetic tendinopathy, including the cAMP signaling pathway and Calcium signaling pathway. Previous studies have shown that Cyclic adenosine monophosphate (cAMP) is an important intracellular second messenger, which plays various physiological roles through the activation of protein kinase A(PKA), and is a key regulatory factor in regulating metabolism and maintaining glucose homeostasis [ 25 ]. cAMP is known to play an important regulatory role in a variety of important physiological and pathological processes, including endothelial angiogenesis [ 26 ], osteoclast function [ 27 ], and reduction of oxidative stress [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics reveals dynamic changes in the “gene profiles” of rat supraspinatus tendon at three different time points after diabetes induction

Xu,

Zhang,

Wang

et al. 2024

BMC Med Genomics

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Objective There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the “gene profile” of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. Methods A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups’ DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Results T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways (p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. Conclusions Transcriptomics reveals dynamic changes in the“gene profiles”of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.

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“…Diabetes has been linked to an elevated hepatic cAMP content in rats [ 61 , 62 ]. This is in line with our data, which revealed elevated cAMP levels in hepatocytes of the prediabetic NZO mice.…”

Section: Discussionmentioning

confidence: 99%

Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model

Liebmann

Pfeifer

Grupe

et al. 2022

IJMS

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Female New Zealand obese (NZO) mice are an established model of preconceptional (pc.) prediabetes that progresses as gestational diabetes mellitus (GDM) during gestation. It is known that NZO mice show improvement in insulin sensitivity and glucose-stimulated insulin secretion (GSIS) during gestation in vivo. The latter is no longer detectable in ex vivo perifusion experiments in isolated islets of Langerhans, suggesting a modulation by extrapancreatic factors. Here, we demonstrated that plasma 17β-estradiol (E2) levels increased markedly in NZO mice during gestation. The aim of this work was to determine whether these increased E2 levels are responsible for the improvement in metabolism during gestation. To achieve this goal, we examined its effects in isolated islets and primary hepatocytes of both NZO and metabolically healthy NMRI mice. E2 increased GSIS in the islets of both strains significantly. Hepatic glucose production (HGP) failed to be decreased by insulin in NZO hepatocytes but was reduced by E2 in both strains. Hepatocytes of pregnant NZO mice showed significantly lower glucose uptake (HGU) compared with NMRI controls, whereby E2 stimulation diminished this difference. Hepatocytes of pregnant NZO showed reduced glycogen content, increased cyclic adenosine monophosphate (cAMP) levels, and reduced AKT activation. These differences were abolished after E2 stimulation. In conclusion, our data indicate that E2 stabilizes and prevents deterioration of the metabolic state of the prediabetic NZO mice. E2 particularly increases GSIS and improves hepatic glucose utilization to a lower extent.

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Dietary Bioactive Ingredients Modulating the cAMP Signaling in Diabetes Treatment

Cited by 7 publications

References 125 publications

Olfr78, a novel short‐chain fatty acid receptor, regulates glucose homeostasis and gut GLP‐1 secretion in mice

Olfr78, a novel short‐chain fatty acid receptor, regulates glucose homeostasis and gut GLP‐1 secretion in mice

Transcriptomics reveals dynamic changes in the “gene profiles” of rat supraspinatus tendon at three different time points after diabetes induction

Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model

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