Gastric inhibitory polypeptide/glucose‐dependent insulinotropic polypeptide signaling in adipose tissue

Yamane, Shunsuke; Harada, Norio

doi:10.1111/jdi.12942

Cited by 9 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GIP is secreted from enteroendocrine K cells of the upper small intestine ( Iwasaki et al., 2015 ). LCT ingestion strongly induces GIP secretion, and GIP hypersecretion contributes to the development of obesity and insulin resistance ( Harada et al., 2008 , 2011 ; Joo et al., 2017 ; Shimazu-Kuwahara et al., 2017 ; Yamane and Harada, 2019 ). In contrast, studies using GIP -overexpressing mice or GIP agonist have shown that pharmacological activation of GIP signaling is beneficial for suppression of body weight gain and insulin resistance ( Kim et al., 2012 ; Mroz et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK

et al. 2021

Self Cite

View full text Add to dashboard Cite

Summary Long-chain triglycerides (LCTs) intake strongly stimulates GIP secretion from enteroendocrine K cells and induces obesity and insulin resistance partly due to GIP hypersecretion. In this study, we found that medium-chain triglycerides (MCTs) inhibit GIP secretion after single LCT ingestion and clarified the mechanism underlying MCT-induced inhibition of GIP secretion. MCTs reduced the CCK effect after single LCT ingestion in wild-type (WT) mice, and a CCK agonist completely reversed MCT-induced inhibition of GIP secretion. In vitro studies showed that medium-chain fatty acids (MCFAs) inhibit long-chain fatty acid (LCFA)-stimulated CCK secretion and increase in intracellular Ca 2+ concentrations through inhibition of GPR120 signaling. Long-term administration of MCTs reduced obesity and insulin resistance in high-LCT diet-fed WT mice, but not in high-LCT diet-fed GIP -knockout mice. Thus, MCT-induced inhibition of GIP hypersecretion reduces obesity and insulin resistance under high-LCT diet feeding condition.

show abstract

Section: Introductionmentioning

confidence: 99%

Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The plausibility of a causal effect of fasting circulating GIP on reducing insulin sensitivity and promoting β-cell function is supported by evidence from other studies [ 39 , 40 ]. GIP is an incretin secreted post-prandially by enteroendocrine K-cells found in the gastrointestinal tract, stomach, and pancreas [ 41 ]. GIP stimulates the release of insulin from pancreatic β-cells, which facilitates the storage and clearance of dietary triglycerides as well as adipose tissue expansion [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…GIP is an incretin secreted post-prandially by enteroendocrine K-cells found in the gastrointestinal tract, stomach, and pancreas [ 41 ]. GIP stimulates the release of insulin from pancreatic β-cells, which facilitates the storage and clearance of dietary triglycerides as well as adipose tissue expansion [ 41 ]. High-fat diets in mice were found to induce hypersecretion of GIP [ 42 ], and these increased GIP levels have been proposed to play an important role in the reduced insulin sensitivity that is observed in the presence of high-fat-diet consumption and elevated BMI [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analyses suggest a causal role for circulating GIP and IL-1RA levels in homeostatic model assessment-derived measures of β-cell function and insulin sensitivity in Africans without type 2 diabetes

Meeks,

Bentley,

Assimes

et al. 2023

Genome Med

View full text Add to dashboard Cite

Background In vitro and in vivo studies have shown that certain cytokines and hormones may play a role in the development and progression of type 2 diabetes (T2D). However, studies on their role in T2D in humans are scarce. We evaluated associations between 11 circulating cytokines and hormones with T2D among a population of sub-Saharan Africans and tested for causal relationships using Mendelian randomization (MR) analyses. Methods We used logistic regression analysis adjusted for age, sex, body mass index, and recruitment country to regress levels of 11 cytokines and hormones (adipsin, leptin, visfatin, PAI-1, GIP, GLP-1, ghrelin, resistin, IL-6, IL-10, IL-1RA) on T2D among Ghanaians, Nigerians, and Kenyans from the Africa America Diabetes Mellitus study including 2276 individuals with T2D and 2790 non-T2D individuals. Similar linear regression models were fitted with homeostatic modelling assessments of insulin sensitivity (HOMA-S) and β-cell function (HOMA-B) as dependent variables among non-T2D individuals (n = 2790). We used 35 genetic variants previously associated with at least one of these 11 cytokines and hormones among non-T2D individuals as instrumental variables in univariable and multivariable MR analyses. Statistical significance was set at 0.0045 (0.05/11 cytokines and hormones). Results Circulating GIP and IL-1RA levels were associated with T2D. Nine of the 11 cytokines and hormones (exceptions GLP-1 and IL-6) were associated with HOMA-S, HOMA-B, or both among non-T2D individuals. Two-stage least squares MR analysis provided evidence for a causal effect of GIP and IL-RA on HOMA-S and HOMA-B in multivariable analyses (GIP ~ HOMA-S β = − 0.67, P-value = 1.88 × 10−6 and HOMA-B β = 0.59, P-value = 1.88 × 10−5; IL-1RA ~ HOMA-S β = − 0.51, P-value = 8.49 × 10−5 and HOMA-B β = 0.48, P-value = 5.71 × 10−4). IL-RA was partly mediated via BMI (30-34%), but GIP was not. Inverse variance weighted MR analysis provided evidence for a causal effect of adipsin on T2D (multivariable OR = 1.83, P-value = 9.79 × 10−6), though these associations were not consistent in all sensitivity analyses. Conclusions The findings of this comprehensive MR analysis indicate that circulating GIP and IL-1RA levels are causal for reduced insulin sensitivity and increased β-cell function. GIP’s effect being independent of BMI suggests that circulating levels of GIP could be a promising early biomarker for T2D risk. Our MR analyses do not provide conclusive evidence for a causal role of other circulating cytokines in T2D among sub-Saharan Africans.

show abstract

“…However, it seems that GIP is of significant importance in the development of obesity and its complications, through interactions with various body organs. The hypothesis was raised that GIP signaling participates in the development of hepatic steatosis [30]. Thus, our study aimed to investigate whether enhanced secretion of GIP in obese humans may affect markers of liver injury, liver targeted FGFs, and plasma miRNA profile.…”

Section: Discussionmentioning

confidence: 99%

“…The results reported by Junker showed that non-diabetic patients with NAFLD have normal secretion of GIP and GLP-1, but a reduced incretin effect, although patients with cirrhosis have elevated concentrations of GIP and GLP-1, and a reduced incretin effect [54,55]. Recent papers underlie an important role of GIPR signaling in adipose tissue in HFD-induced insulin resistance and hepatic steatosis in vivo with no direct effect on fat accumulation [30]. It was shown that deletion of GIPR signaling in adipocytes results in the decrease in interleukin (IL)-6 production in adipose tissue and subsequent decrease in fat synthesis in the liver through the IL-6-SOCS3-SREBP-1c pathway.…”

Section: Discussionmentioning

confidence: 99%

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

et al. 2020

View full text Add to dashboard Cite

Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25–40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01–0.32)], triglycerides [β = 0.21 (95% CI: 0.06–0.36], and FGF-21 [β = 0.20 (95%CI: 0.03–0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03–0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02–5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut–liver cross-talk.

show abstract

Gastric inhibitory polypeptide/glucose‐dependent insulinotropic polypeptide signaling in adipose tissue

Abstract: GIPR signaling in adipose tissue plays an important role in HFD‐induced insulin resistance and hepatic steatosis in vivo, with no direct effect on fat accumulation, through IL‐6 signaling

Cited by 9 publications

References 20 publications

Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK

Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK

Mendelian randomization analyses suggest a causal role for circulating GIP and IL-1RA levels in homeostatic model assessment-derived measures of β-cell function and insulin sensitivity in Africans without type 2 diabetes

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

Contact Info

Product

Resources

About