scholarly journals FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans

2017 ◽  
Vol 102 (10) ◽  
pp. 3806-3813 ◽  
Author(s):  
Ricardo J Samms ◽  
Jo E Lewis ◽  
Luke Norton ◽  
Francis B Stephens ◽  
Christopher J Gaffney ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fibroblast Growth Factor 21 ◽  
Oral Glucose ◽  
High Fat ◽  
Postprandial Period ◽  
Carbohydrate Consumption ◽  
Adult Humans ◽  
The Impact

Abstract Context Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose, and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin. Objective The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action. Methods Circulating glucose, insulin, total and bioactive FGF21, and fibroblast activation protein were measured in adults with and without type 2 diabetes (T2D) following an oral glucose tolerance test (OGTT), and under a series of insulin and glucose clamp conditions and following high-fat diet in healthy adults. Results Circulating total and bioactive FGF21 levels responded acutely to OGTT, and their ratio was attenuated in T2D patients with reduced postprandial insulin response. The clamp studies revealed that insulin but not glucose accounts for the postprandial rise in FGF21. Finally, there was an attenuated rise in FGF21 in response to a high-fat dietary intervention that is known to alter insulin-stimulated substrate utilization in metabolically active tissues. Conclusions Insulin rather than glucose per se increases total and bioactive FGF21 in the postprandial period in adult humans. Understanding the impact of T2D on bioactive FGF21 will have a significant effect upon the efficacy of therapeutic agents designed to target the FGF21 pathway.

scholarly journals PL-017 High-fat overfeeding increases intramuscular triglyceride content and perilipin protein expression in human skeletal muscle

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Katie Whytock ◽  
Siôn Parry ◽  
Mark Turner ◽  
Lewis James ◽  
Richard Fergusson ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Insulin Signalling ◽  
Tolerance Test ◽  
Whole Body ◽  
Future Research ◽  
Oral Glucose ◽  
Type I ◽  
High Fat ◽  
Intramuscular Triglyceride ◽  
High Calorie

Objective High-fat high-calorie diets can induce whole body insulin resistance (IR) whilst increasing stores of intramuscular triglyceride (IMTG) contained within lipid droplets (LD). Perilipin (PLIN) proteins assist in IMTG storage. Synaptosomal-associated protein (SNAP23) may support LD growth and also direct IMTG-derived fatty acids (FA) to mitochondria for β-oxidation. The objectives of this study were: 1) to test the hypothesis that 7 days of high-fat overfeeding increases IMTG content to prevent lipid induced muscle IR and 2) identify changes in PLINs, SNAP23 and mitochondria content and colocalisation of PLINs with LD, and SNAP23 with LD and mitochondria. Methods Muscle biopsies were obtained from thevastus lateralisof thirteen healthy individuals (age: 23±1years, BMI: 24.4±0.7kg.m-2) before (0min) and during (30min) an oral glucose tolerance test (OGTT), pre and post 7-days consuming a high-fat (65% energy) high-calorie (+50% kcal) diet. IMTG, PLIN2, PLIN3, PLIN5, SNAP23 and mitochondria content were measured using (semi)-quantitative confocal immunofluorescence microscopy. PLIN2, PLIN3 and PLIN5 colocalisation to LD was measured using object-based colocalisation analyses. Pearson’s correlation coefficient quantified colocalisation between SNAP23 and plasma membrane (PM), mitochondria and LD. Phosphorylation of intermediates of the muscle insulin-signalling cascade (Akt and AS160) were measured at 0 and 30 min of the OGTT before and after the dietary intervention. Results Following overfeeding phosphorylation of Akt and AS160 in muscle was not impaired during the OGTT, however Matsuda index of whole-body insulin sensitivity decreased (-23%; P < 0.01). IMTG content increased in type I fibres (+100%; P < 0.001) due to both an increase in LD number (+43%; P < 0.001) and size (+44%; P< 0.001). Of the PLINs investigated, only PLIN3 content increased (+50%;P < 0.01) exclusively in type I fibres. PLIN2-associated LD increased (+80%; P < 0.01) in type I fibres only, whereas PLIN3 and PLIN5-associated LD were unaltered. SNAP23 and mitochondria content did not change, nor did the colocalisation of SNAP23 with the PM, mitochondria or LD. Conclusions Our data confirm the hypothesis that following high-fat overfeeding IMTG stores increased whilst activation of key muscle insulin signalling components were maintained. The increase in IMTG stores is likely supported by the concurrent increase in total PLIN3 content and a redistribution of existing stores of PLIN2 to the expanded LD pool in type I fibres. To confirm if increased IMTG storage protects muscle from IR future research should determine whether meal-derived FAs are directed to IMTG rather than ceramides and diacylglycerol.

The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy

2019 ◽  
Vol 123 (5) ◽  
pp. 516-528 ◽  
Author(s):  
J. F. Plows ◽  
J. M. Ramos Nieves ◽  
F. Budin ◽  
K. Mace ◽  
C. M. Reynolds ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Lactobacillus Rhamnosus ◽  
Tissue Expression ◽  
Tolerance Test ◽  
Preclinical Model ◽  
Oral Glucose ◽  
High Fat ◽  
The Impact

AbstractGlucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: a Multi-Center Cohort Study

2021 ◽  
Author(s):  
Rain Yamamoto ◽  
Majken K Jensen ◽  
Sarah Aroner ◽  
Jeremy D Furtado ◽  
Bernard Rosner ◽  
...  
Keyword(s):  
Cohort Study ◽  
Insulin Sensitivity ◽  
Clinical Investigation ◽  
Biological Effects ◽  
Sandwich Elisa ◽  
Insulin Response ◽  
Protein Composition ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Euglycemic Hyperinsulinemic Clamp

Abstract Context HDL in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. Objective We investigated the prospective associations between HDL subspecies containing and lacking apoC-III at baseline and insulin sensitivity at year 3. Design, Setting, and Participants A prospective cohort study of 864 healthy volunteers drawn from the RISC study, a multi-center European clinical investigation, whose recruitment initiated in 2002 with a follow-up of 3 years. Main Measures Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT) at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich ELISA-based method. Results The two HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (p-heterogeneity=0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (p-trend=0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (p-trend=0.01), compared to the lowest quintile. No significant association was observed for total HDL, and VLDL and LDL containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. Conclusion Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.

scholarly journals Histologic and Metabolic Derangement in High-Fat, High-Fructose, and Combination Diet Animal Models

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jai Sun Lee ◽  
Dae Won Jun ◽  
Eun Kyung Kim ◽  
Hye Joon Jeon ◽  
Ho Hyun Nam ◽  
...  
Keyword(s):  
Animal Model ◽  
Body Weight Gain ◽  
Tolerance Test ◽  
Combination Group ◽  
Oral Glucose ◽  
High Fat ◽  
Metabolic Derangement ◽  
Fat Accumulation ◽  
Nonalcoholic Fatty Liver ◽  
High Fructose

Background. We used high-fat (HF), high-fructose (HFr), and combination diets to create a dietary animal model of nonalcoholic fatty liver disease (NAFLD). Comparison of both clinical phenotypes has not been well defined. The purpose of this study was to compare histologic and metabolic characteristics between diets in an animal model of NAFLD.Methods. NAFLD was induced in rats by feeding them HF, HFr, and combination (HF + HFr) diets for 20 weeks. The degree of intrahepatic fat accumulation, inflammation, and oxidative stress was evaluated. Metabolic derangements were assessed by the oral glucose tolerance test and the intrahepatic insulin signal pathway.Results. Body weight gain and intrahepatic fat accumulation were more prominent in the HF feeding group than in the HFr group. The expressions of NOX-4 and TLR-4 were higher in the HF and HFr combination groups than in the HF-only group. Other intrahepatic inflammatory markers, MCP-1, TNF-α, and endoplasmic reticulum stress markers, were the highest in the HF + HFr combination group. Although intrahepatic fat deposition was less prominent in the HFr diet model, intrahepatic inflammation was noted.Conclusions. Intrahepatic inflammation and metabolic derangements were more prominent in the HF and HFr combination model than in the HF monodiet model.

scholarly journals Effects of Weight Loss on FGF-21 in Human Subjects: An Exploratory Study

2019 ◽  
Vol 16 (23) ◽  
pp. 4877
Author(s):  
Headland ◽  
Clifton ◽  
Keogh
Keyword(s):  
Weight Loss ◽  
Exploratory Study ◽  
Wound Repair ◽  
Dietary Intervention ◽  
Human Subjects ◽  
Restriction Pattern ◽  
Energy Restriction ◽  
Fibroblast Growth Factor 21 ◽  
Continuous Energy ◽  
The Impact

Fibroblast growth factor-21 (FGF-21), is a protein involved in cell growth and differentiation, development, wound repair and metabolism. Research looking at the impact of weight loss on FGF-21 levels is limited. The objective of this exploratory study was to determine changes in serum FGF-21 levels following weight loss induced by either continuous energy restriction or intermittent energy restriction. A sub cohort of participants who completed a 12-month dietary intervention trial following continuous energy restriction, or a week-on week-off energy restriction pattern, were selected for analysis. FGF-21 levels were not altered by weight loss and were not correlated with body weight or BMI at baseline or 12 months. Weight loss after 12 months either through continuous energy restriction or intermittent energy restriction was −5.9 ± 4.5 and −4.9 ± 3.4 kg, respectively. There was no change in FGF-21 levels, 0.3 ± 0.9 and 0.04 ± 0.2 ng/mL (p = 0.2). In conclusion, weight loss in healthy overweight or obesity subjects did not affect FGF-21 levels.

Probiotics lower plasma glucose in the high-fat fed C57BL/6J mouse

2010 ◽  
Vol 1 (2) ◽  
pp. 189-196 ◽  
Author(s):  
U. Andersson ◽  
C. Bränning ◽  
S. Ahrné ◽  
G. Molin ◽  
J. Alenfall ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Plasma Glucose ◽  
Short Chain Fatty Acids ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Control Group ◽  
Oral Glucose ◽  
Gut Health ◽  
High Fat ◽  
Early Diabetes

Today, the gut microbiota is considered a key organ in host nutritional metabolism and recent data have suggested that alterations in gut microbiota contribute to the development of type 2 diabetes and obesity. Accordingly, a whole range of beneficial effects relating to inflammation and gut health have been observed following administration of probiotics to both humans and different animal models. The objective of this study was to evaluate the metabolic effects of an oral probiotic supplement, Lactobacillus plantarum DSM 15313, to high-fat diet (HFD) fed C57BL/6J mice, a model of human obesity and early diabetes. The mice were fed the experimental diets for 20 weeks, after which the HFD had induced an insulin-resistant state in both groups compared to the start of the study. The increase in body weight during the HFD feeding was higher in the probiotic group than in the control group, however, there were no significant differences in body fat content. Fasting plasma glucose levels were lower in the group fed the probiotic supplement, whereas insulin and lipids were not different. Caecal levels of short-chain fatty acids were not significantly different between the groups. An oral glucose tolerance test showed that the group fed probiotics had a significantly lower insulin release compared to the control group, although the rate of glucose clearance was not different. Taken together, these data indicate that L. plantarum DSM 15313 has anti-diabetic properties when fed together with an HFD.

scholarly journals Fructose Consumption Contributes to Hyperinsulinemia in Adolescents With Obesity Through a GLP-1–Mediated Mechanism

2019 ◽  
Vol 104 (8) ◽  
pp. 3481-3490 ◽  
Author(s):  
Alfonso Galderisi ◽  
Cosimo Giannini ◽  
Michelle Van Name ◽  
Sonia Caprio
Keyword(s):  
Glucose Tolerance ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Cell Function ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Double Blind ◽  
Obesity And Diabetes ◽  
Glucose Ingestion

Abstract Context The consumption of high-fructose beverages is associated with a higher risk for obesity and diabetes. Fructose can stimulate glucagon-like peptide 1 (GLP-1) secretion in lean adults, in the absence of any anorexic effect. Objective We hypothesized that the ingestion of glucose and fructose may differentially stimulate GLP-1 and insulin response in lean adolescents and adolescents with obesity. Design We studied 14 lean adolescents [four females; 15.9 ± 1.6 years of age; body mass index (BMI), 21.8 ± 2.2 kg/m2] and 23 adolescents with obesity (five females; 15.1 ± 1.6 years of age; BMI, 34.5 ± 4.6 kg/m2). Participants underwent a baseline oral glucose tolerance test to determine their glucose tolerance and estimate insulin sensitivity and β-cell function [oral disposition index (oDIcpep)]. Eligible subjects received, in a double-blind, crossover design, 75 g of glucose or fructose. Plasma was obtained every 10 minutes for 60 minutes for the measures of glucose, insulin, and GLP-1 (radioimmunoassay) and glucose-dependent insulinotropic polypeptide (GIP; ELISA). Incremental glucose and hormone levels were compared between lean individuals and those with obesity by a linear mixed model. The relationship between GLP-1 increment and oDIcpep was evaluated by regression analysis. Results Following the fructose challenge, plasma glucose excursions were similar in both groups, yet the adolescents with obesity exhibited a greater insulin (P &lt; 0.001) and GLP-1 (P &lt; 0.001) increase than did their lean peers. Changes in GIP were similar in both groups. After glucose ingestion, the GLP-1 response (P &lt; 0.001) was higher in the lean group. The GLP-1 increment during 60 minutes from fructose drink was correlated with a lower oDIcpep (r2 = 0.22, P = 0.009). Conclusion Fructose, but not glucose, ingestion elicits a higher GLP-1 and insulin response in adolescents with obesity than in lean adolescents. Fructose consumption may contribute to the hyperinsulinemic phenotype of adolescent obesity through a GLP-1–mediated mechanism.

scholarly journals The SLC16A11 Risk Haplotype for Type 2 Diabetes (T2D) Is Associated to Differentiated Responses in Weight Loss, and Glucose Metabolism After Treatments to Prevent T2D

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1275-1275
Author(s):  
Magdalena Sevilla ◽  
Donaji Gomez-Velasco ◽  
Ivette Cruz-Bautista ◽  
Laura Lazaro-Carrera ◽  
Paloma Almeda-Valdes ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Prolonged Release ◽  
Risk Haplotype ◽  
The Impact

Abstract Objectives A haplotype in SLC16A11 is associated with decreased insulin action, and risk for type 2 diabetes (T2D) in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D. Methods We recruited subjects with at least one prediabetes criteria according to the American Diabetes Association, and body mass index 25–45 kg/m2. Subjects were randomized in two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids and 15% protein sources + physical activity (&gt;150 min medium intensity per week), or LSI + metformin (750 mg prolonged release twice a day). Interventions were prescribed by standardized dietitians. The goal was to achieve &gt;3% weight loss. We evaluated the early treatment response in a follow-up period of 12 weeks with intermediate visits each 3 weeks to reinforce knowledge and treatment goals. Evaluations (baseline and post-treatment) included an oral glucose tolerance test (OGTT), and dual-energy X-ray absorptiometry. Adherence to treatment was measured trough electronic recordings. Participants were genotyped for the risk allele rs13342232. Researchers remained blinded to the genotype results. The effects of the risk haplotype were evaluated with linear and logistic regressions adjusted by age, sex, and baseline body fat %. Results We evaluated 61 subjects, 30 carriers, and 31 non-carriers. Most of participants (57%) achieved ≥3% weight loss. The LSI + metformin treatment increased in carriers, 2 times OR 3 IC95% (1.07 – 8.6) (P = 0.04) the probability to reach the ≥3% weight loss goal compared with LSI and non-carriers. In the same treatment, carriers had a greater decrease in the total and incremental area under the curve of insulin in the OGTT IC95% (−1.75 −0.11) (P = 0.02) compared with non-carriers and LSI. Carriers also had higher decrease in postprandial glucose compared with non-carriers regardless of treatment −12.63 + 30.38 vs 0.71 30.24 (P = 0.02). Conclusions After 12 weeks of treatment, carriers with prediabetes showed a higher probability achieve weight loss and to improve insulin secretion with metformin. Regardless of the treatment, carriers were prone to improve postprandial glucose. Funding Sources Miguel Aleman Medical Research Award.

Sign in / Sign up

Export Citation Format

Share Document