scholarly journals Increased Plasma FGF21 and Activated FGF21 Signaling in Adipose Tissue and Its Possible Association With Insulin Sensitivity in Specific GDM Subtype

2021 ◽  
Author(s):  
Ning WANG ◽  
Bo SUN ◽  
Mengjun WANG ◽  
Yang MI ◽  
Huan CHEN ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Fasting Blood Glucose ◽  
Normal Glucose Tolerance ◽  
Gene Expressions ◽  
Fgf Receptor ◽  
Ppar Γ ◽  
Fgf21 Level ◽  
Normal Glucose ◽  
Beta Gene

Abstract Background: To study the discrepancy of the insulin sensitivity alteration pattern, circulating fibroblast growth factor (FGF21) levels and FGF21 signaling in visceral white adipose tissue (vWAT) of gestational diabetes mellitus (GDM) subtypes.Methods: 26 GDM women with either a predominant of insulin-secretion defect (GDM-dysfunction, n = 9) or insulin-sensitivity defect (GDM-resistance, n = 17)] and 13 normal glucose tolerance (NGT) women scheduled for caesarean-section at term were studied. Plasma and vWAT samples were collected at delivery.Results: The insulin sensitivity was improved from the 2nd trimester to delivery in the GDM-resistance group. Elevated circulating FGF21 concentration at delivery, increased FGF receptor 1c and decreased klotho beta gene expressions, enhanced ERK1/2 phosphorylation, and increased GLUT1, IR-B, PPAR-γ gene expressions in vWAT were found in the GDM-resistance group as compared with the NGT group. The circulating FGF21 concentration was negatively correlated with fasting blood glucose (r = -0.574, P < 0.001), and associated with the GDM-resistance group (r = 0.574, P < 0.001) in pregnant women at delivery. However, we observed no insulin sensitivity alteration in GDM-dysfunction and NGT groups during pregnancy. No differences of plasma FGF21 level and FGF21 signaling in vWAT at delivery were found between women in the GDM-dysfunction and the NGT group. Conclusions: Women with GDM heterogeneity exhibited different insulin sensitivity alteration patterns. The improvement of insulin sensitivity may relate to the elevated circulating FGF21 concentration and activated FGF21 signaling in vWAT at delivery in the GDM-resistance group.Trial registration: ChiCTR, ChiCTR 1900026735, registered 20 October 2019, https://www.chictr.org.cn/25/showproj.aspx?proj=44559

scholarly journals Association of Elevated Plasma FGF21 and Activated FGF21 Signaling in Visceral White Adipose Tissue and Improved Insulin Sensitivity in Gestational Diabetes Mellitus Subtype: A Case-Control Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Wang ◽  
Bo Sun ◽  
Haonan Guo ◽  
Yingyu Jing ◽  
Qi Ruan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
White Adipose Tissue ◽  
Fasting Blood Glucose ◽  
Normal Glucose Tolerance ◽  
Fgf Receptor

ObjectiveTo study the discrepancy of the insulin sensitivity alteration pattern, circulating fibroblast growth factor (FGF21) levels and FGF21 signaling in visceral white adipose tissue (vWAT) of gestational diabetes mellitus (GDM) subtypes.Methods26 GDM women with either a predominant of insulin-secretion defect (GDM-dysfunction, n = 9) or insulin-sensitivity defect (GDM-resistance, n = 17) and 13 normal glucose tolerance (NGT) women scheduled for caesarean-section at term were studied. Blood and vWAT samples were collected at delivery.ResultsThe insulin sensitivity was improved from the 2nd trimester to delivery in the GDM-resistance group. Elevated circulating FGF21 concentration at delivery, increased FGF receptor 1c and decreased klotho beta gene expression, enhanced ERK1/2 phosphorylation, and increased GLUT1, IR-B, PPAR-γ gene expression in vWAT were found in the GDM-resistance group as compared with the NGT group. The circulating FGF21 concentration was negatively correlated with fasting blood glucose (r = -0.574, P &lt; 0.001), and associated with the GDM-resistance group (r = 0.574, P &lt; 0.001) in pregnant women at delivery. However, we observed no insulin sensitivity alteration in GDM-dysfunction and NGT groups during pregnancy. No differences of plasma FGF21 level and FGF21 signaling in vWAT at delivery were found between women in the GDM-dysfunction and the NGT group.ConclusionsWomen with GDM heterogeneity exhibited different insulin sensitivity alteration patterns. The improvement of insulin sensitivity may relate to the elevated circulating FGF21 concentration and activated FGF21 signaling in vWAT at delivery in the GDM-resistance group.

scholarly journals Differences in the link between insulin sensitivity and ectopic fat in men of Black African and White European ethnicity

2020 ◽  
Vol 182 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Oluwatoyosi Bello ◽  
Meera Ladwa ◽  
Olah Hakim ◽  
Chinmay Marathe ◽  
Fariba Shojaee-Moradie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Normal Glucose Tolerance ◽  
Whole Body ◽  
Ectopic Fat ◽  
Black African ◽  
Hepatic Insulin Sensitivity ◽  
Normal Glucose ◽  
Skeletal Muscle Insulin Sensitivity ◽  
Ectopic Fat Deposition

Objectives In men of black west African (BAM) and white European (WEM) ethnicity, we aimed to (1) compare adipose tissue, peripheral and hepatic insulin sensitivity and (2) investigate associations between ectopic fat and insulin sensitivity by ethnicity. Design and methods In overweight BAM (n = 21) and WEM (n = 23) with normal glucose tolerance, we performed a two-step hyperinsulinaemic–euglycaemic clamp with infusion of [6,6 2H2]-glucose and [2H5]-glycerol to measure whole body, peripheral, hepatic and adipose tissue insulin sensitivity (lipolysis). Visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular (IMCL) lipids were measured using MRI and spectroscopy. Associations between insulin sensitivity and ectopic fat were assessed using Pearson’s correlation coefficient by ethnicity and regression analysis. Results There were no ethnic differences in whole body or tissue-specific insulin sensitivity (all P  > 0.05). Suppression of lipolysis was inversely associated with VAT and IHL in WEM but not BAM (VAT: WEM r = −0.68, P < 0.01; BAM r = 0.07, P = 0.79. IHL: WEM r = −0.52, P = 0.01; BAM r = −0.12, P = 0.63). IMCL was inversely associated with skeletal muscle insulin sensitivity in WEM but not BAM (WEM r = −0.56, P < 0.01; BAM r = −0.09, P = 0.75) and IHL was inversely associated with hepatic insulin sensitivity in WEM but not BAM (WEM r = −0.53, P = 0.02; BAM r = −0.13, P = 0.62). Conclusions Ectopic fat deposition may play a lesser role in reducing insulin sensitivity in men of black African ethnicity and may not be driven by lipolysis. Resistance to storing VAT, IHL and IMCL may enable men of black African ethnicity to maintain comparable insulin sensitivity to white Europeans.

scholarly journals Prep1 Deficiency Induces Protection from Diabetes and Increased Insulin Sensitivity through a p160-Mediated Mechanism

2008 ◽  
Vol 28 (18) ◽  
pp. 5634-5645 ◽  
Author(s):  
Francesco Oriente ◽  
Luis Cesar Fernandez Diaz ◽  
Claudia Miele ◽  
Salvatore Iovino ◽  
Silvia Mori ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Normal Glucose Tolerance ◽  
Glucose Disposal ◽  
Protein Levels ◽  
Normal Glucose ◽  
Enhanced Expression ◽  
The Stability

ABSTRACT We have examined glucose homeostasis in mice hypomorphic for the homeotic transcription factor gene Prep1. Prep1-hypomorphic (Prep1 i / i ) mice exhibit an absolute reduction in circulating insulin levels but normal glucose tolerance. In addition, these mice exhibit protection from streptozotocin-induced diabetes and enhanced insulin sensitivity with improved glucose uptake and insulin-dependent glucose disposal by skeletal muscle. This muscle phenotype does not depend on reduced expression of the known Prep1 transcription partner, Pbx1. Instead, in Prep1 i / i muscle, we find normal Pbx1 but reduced levels of the recently identified novel Prep1 interactor p160. Consistent with this reduction, we find a muscle-selective increase in mRNA and protein levels of PGC-1α, accompanied by enhanced expression of the GLUT4 transporter, responsible for insulin-stimulated glucose uptake in muscle. Indeed, using L6 skeletal muscle cells, we induced the opposite effects by overexpressing Prep1 or p160, but not Pbx1. In vivo skeletal muscle delivery of p160 cDNA in Prep1 i / i mice also reverses the molecular phenotype. Finally, we show that Prep1 controls the stability of the p160 protein. We conclude that Prep1 controls insulin sensitivity through the p160-GLUT4 pathway.

scholarly journals Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance

2021 ◽  
Vol 8 ◽  
Author(s):  
Kiriko Watanabe ◽  
Moritake Higa ◽  
Yoshimasa Hasegawa ◽  
Akihiro Kudo ◽  
Richard C. Allsopp ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Regional Differences ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Sensitivity Index ◽  
Insulinogenic Index ◽  
Genetic Traits ◽  
Normal Glucose

Purpose: Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants.Methods: This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database.Results: Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulinAUC/glucoseAUC or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber.Conclusions: We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.

scholarly journals Circulating betatrophin/ANGPTL8 levels correlate with body fat distribution in individuals with normal glucose tolerance but not those with glucose disorders

2019 ◽  
Author(s):  
Jing Zheng ◽  
Juan Liu ◽  
Beverly S Hong ◽  
Yanbing Li
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Lower Limb ◽  
Fat Distribution ◽  
Normal Glucose Tolerance ◽  
Body Fat Distribution ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Glucose

Abstract Background: The relationship between betatrophin/ANGPTL8 and obesity has been investigated using body mass index (BMI); however, since BMI reflects overall adiposity rather than body fat distribution, it remains unclear whether fat deposition in different areas of the body affects betatrophin expression. Here, we investigated the correlation between circulating betatrophin levels and body fat distribution in patients with different glucose tolerance. Methods: In 128 participants with impaired glucose tolerance (IGT; n = 64) or normal glucose tolerance (NGT; n = 64), we measured circulating betatrophin levels by enzyme-linked immunosorbent assay and body fat distribution (subcutaneous, visceral, and limb fat) using magnetic resonance imaging (MRI) and a body fat meter. Results: After controlling for age, sex, and BMI, betatrophin was correlated positively with visceral adipose tissue-to-subcutaneous adipose tissue ratio ( VAT/SAT ratio; r = 0.339, p = 0.009) and negatively with body fat ratio (BFR; r = -0.275, p = 0.035), left lower limb fat ratio (LLR; r = -0.330, p = 0.011), and right lower limb fat ratio (RLR; r = -0.288, p = 0.027) in the NGT group, with these correlations remaining after controlling for triglycerides. VAT/SAT ratio (standardized β = 0.419, p = 0.001) was independently associated with serum betatrophin levels; however, betatrophin was not associated with body fat distribution variables in the IGT group. Conclusions: Circulating betatrophin levels correlated positively with VAT/SAT ratio and negatively with lower limb fat, but not subcutaneous or upper limb fat, in individuals with normal glucose tolerance. Thus, betatrophin may be a poten­tial biomarker for body fat distribution in individuals without glucose disorders.

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