scholarly journals CD47 Deficiency Protects Mice From Diet-induced Obesity and Improves Whole Body Glucose Tolerance and Insulin Sensitivity

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Hasiyeti Maimaitiyiming ◽  
Heather Norman ◽  
Qi Zhou ◽  
Shuxia Wang
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Whole Body ◽  
Diet Induced Obesity

DPP4 deletion in adipose tissue improves hepatic insulin sensitivity in diet-induced obesity

2020 ◽  
Vol 318 (5) ◽  
pp. E590-E599 ◽  
Author(s):  
Tania Romacho ◽  
Henrike Sell ◽  
Ira Indrakusuma ◽  
Diana Roehrborn ◽  
Tamara R. Castañeda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hepatic Insulin Sensitivity ◽  
Dipeptidyl Peptidase 4 ◽  
Diet Induced Obesity ◽  
Hepatic Fat ◽  
Igf Binding ◽  
Igf Binding Protein

Besides a therapeutic target for type 2 diabetes, dipeptidyl peptidase 4 (DPP4) is an adipokine potentially upregulated in human obesity. We aimed to explore the role of adipocyte-derived DPP4 in diet-induced obesity and insulin resistance with an adipose tissue-specific knockout (AT-DPP4-KO) mouse. Wild-type and AT-DPP4-KO mice were fed for 24 wk with a high fat diet (HFD) and characterized for body weight, glucose tolerance, insulin sensitivity by hyperinsulinemic-euglycemic clamp, and body composition and hepatic fat content. Image and molecular biology analysis of inflammation, as well as adipokine secretion, was performed in AT by immunohistochemistry, Western blot, real-time-PCR, and ELISA. Incretin levels were determined by Luminex kits. Under HFD, AT-DPP4-KO displayed markedly reduced circulating DPP4 concentrations, proving AT as a relevant source. Independently of glucose-stimulated incretin hormones, AT-DPP4-KO had improved glucose tolerance and hepatic insulin sensitivity. AT-DPP4-KO displayed smaller adipocytes and increased anti-inflammatory markers. IGF binding protein 3 (IGFBP3) levels were lower in AT and serum, whereas free IGF1 was increased. The absence of adipose DPP4 triggers beneficial AT remodeling with decreased production of IGFBP3 during HFD, likely contributing to the observed, improved hepatic insulin sensitivity.

Expression of FOXC2 in adipose and muscle and its association with whole body insulin sensitivity

2004 ◽  
Vol 287 (4) ◽  
pp. E799-E803 ◽  
Author(s):  
Gina B. Di Gregorio ◽  
Rickard Westergren ◽  
Sven Enerback ◽  
Tong Lu ◽  
Philip A. Kern
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Forkhead Transcription Factor ◽  
Intravenous Glucose ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Tnf Α

FOXC2 is a winged helix/forkhead transcription factor involved in PKA signaling. Overexpression of FOXC2 in the adipose tissue of transgenic mice protected against diet-induced obesity and insulin resistance. We examined the expression of FOXC2 in fat and muscle of nondiabetic humans with varying obesity and insulin sensitivity. There was no relation between body mass index (BMI) and FOXC2 mRNA in either adipose or muscle. There was a strong inverse relation between adipose FOXC2 mRNA and insulin sensitivity, using the frequently sampled intravenous glucose tolerance test ( r = −0.78, P < 0.001). However, there was no relationship between muscle FOXC2 and any measure of insulin sensitivity. To separate insulin resistance from obesity, we examined FOXC2 expression in pairs of subjects who were matched for BMI but who were discordant for insulin sensitivity. Compared with insulin-sensitive subjects, insulin-resistant subjects had threefold higher levels of adipose FOXC2 mRNA ( P = 0.03). In contrast, muscle FOXC2 mRNA expression was no different between insulin-resistant and insulin-sensitive subjects. There was no association of adipose or muscle FOXC2 mRNA with either circulating or adipose-secreted TNF-α, IL-6, leptin, adiponectin, or non-esterified fatty acids. Thus adipose FOXC2 is more highly expressed in insulin-resistant subjects, and this effect is independent of obesity. This association between FOXC2 and insulin resistance may be related to the role of FOXC2 in PKA signaling.

The Effect of Handcycle Ergometer Exercise on Glucose Tolerance in Ambulatory and Non-Ambulatory Adolescents

2017 ◽  
Vol 29 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Kevin R. Short ◽  
April M. Teague ◽  
Jake C. Klein ◽  
Elizabeth Malm-Buatsi ◽  
Dominic Frimberger
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Upper Body ◽  
Whole Body ◽  
Control Group ◽  
Mobility Limitations ◽  
Upper Body Exercise ◽  
Significant Group ◽  
Ergometer Exercise ◽  
The Impact

Purpose:Whole body or leg exercise before a meal can increase insulin sensitivity, but it is unclear whether the same can occur with upper body exercise since a smaller muscle mass is activated. We measured the impact of a single session of handcycle exercise on glucose tolerance and insulin sensitivity.Methods:Nonambulatory (Non-Amb) adolescents with spina bifida or cerebral palsy (4F/3M), or ambulatory peers (Control, 4F/7M) completed 2 glucose tolerance tests on separate days, preceded by either rest or a 35-min bout of moderate-to-vigorous intermittent handcycle exercise.Results:The Non-Amb group had higher body fat (mean ± SD: 38 ± 12%, Control: 24 ± 9, p = .041) but similar VO2peak (17.7 ± 6.1 ml/kg/min, Control: 21.1 ± 7.9). Fasting glucose and insulin were normal for all participants. Compared with the rest trial, exercise resulted in a reduction in glucose area under the curve (11%, p = .008) without a significant group x trial interaction and no difference in the magnitude of change between groups. Insulin sensitivity was increased 16% (p = .028) by exercise in the Control group but was not significantly changed in the Non-Amb group.Conclusion:A single bout of handcycle exercise improves glucose tolerance in adolescents with and without mobility limitations and could therefore help maintain or improve metabolic health.

Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women

2008 ◽  
Vol 33 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Jennifer L. Kuk ◽  
Katherine Kilpatrick ◽  
Lance E. Davidson ◽  
Robert Hudson ◽  
Robert Ross
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Visceral Adipose Tissue ◽  
Skeletal Muscle Mass ◽  
Whole Body ◽  
Men And Women ◽  
Visceral Adipose

The relationship between skeletal muscle mass, visceral adipose tissue, insulin sensitivity, and glucose tolerance was examined in 214 overweight or obese, but otherwise healthy, men (n = 98) and women (n = 116) who participated in various exercise and (or) weight-loss intervention studies. Subjects had a 75 g oral glucose tolerance test and (or) insulin sensitivity measures by a 3 h hyperinsulinemic–euglycemic clamp technique. Whole-body skeletal muscle mass and visceral adipose tissue were measured using a multi-slice magnetic resonance imaging protocol. Total body skeletal muscle mass was not associated with any measure of glucose metabolism in men or women (p > 0.10). These observations remained independent of age and total adiposity. Conversely, visceral adipose tissue was a significant predictor of various measures of glucose metabolism in both men and women with or without control for age and (or) total body fat (p < 0.05). Although skeletal muscle is a primary site for glucose uptake and deposition, these findings suggest that unlike visceral adipose tissue, whole-body skeletal muscle mass per se is not associated with either glucose tolerance or insulin sensitivity in overweight and obese men and women.

Effect of metformin on substrate utilization after exercise training in adults with impaired glucose tolerance

2013 ◽  
Vol 38 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Steven K. Malin ◽  
Barry Braun
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Oxygen Uptake ◽  
Indirect Calorimetry ◽  
Substrate Utilization ◽  
Peak Oxygen Uptake ◽  
Whole Body ◽  
Glucose Kinetics

Metformin attenuates the higher insulin sensitivity that occurs with exercise training. Sixteen people with prediabetes trained for 10 weeks while taking metformin (n = 8) or placebo (n = 8). Substrate utilization was assessed using glucose kinetics and indirect calorimetry. After training, exercise whole-body fat oxidation was higher and glycogen use lower (p < 0.05), with no differences between groups. Blood glucose use was unchanged. Training-induced enhancement of insulin sensitivity (clamp) correlated with higher peak oxygen uptake (r = 0.70; p < 0.05), but was independent of glucose kinetic and substrate metabolism.

scholarly journals Incorporation of Unique, Diet-derived Fatty Acids into Hepatic Tissue Is Associated with Improved Glucose Homeostasis in Aged CD-1 Mice (OR24-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Allison Unger ◽  
Thomas Jetton ◽  
James Whitley ◽  
Jana Kraft
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Hepatic Tissue ◽  
Gas Liquid Chromatography ◽  
Mouse Population ◽  
Echium Oil ◽  
Dairy Fat ◽  
Fa Composition

Abstract Objectives We hypothesized that the chronic consumption of unique dietary FA derived from dairy fat and echium oil, respectively, would affect the FA composition and content of the hepatic tissue and correlate with parameters of glucose homeostasis in an aged, genetically heterogeneous mouse population. Our objectives were to i) measure glucose homeostasis, ii) determine the FA composition of hepatic tissue, and iii) correlate physiologic data and hepatic FA content by diet and sex. Methods From one month of age, CD-1 male and female mice (n = 10/diet/sex) were fed either a high-fat (40% total energy) control diet comprising of the FA composition of the typical U.S. American diet (CO), or an isoenergetic diet with 30% of CO fat replaced with dairy fat (BO) or echium oil (EO) for the study duration of 13 months. Every three months, whole-body glucose homeostasis was assessed (i.e., glucose tolerance and insulin tolerance tests (GTT and ITT, respectively)). At the end of the study, hepatic tissue was collected and analyzed for FA composition via gas-liquid chromatography. Results Hepatic content of stearidonic acid (SDA; 18:4 n-3) and γ-linolenic acid (18:3 n-6) was greatest in EO-fed mice (P < .0001). Mice fed a BO-diet had the greatest hepatic content of total odd- and branched-chain FA (OBCFA) and conjugated linoleic acids (P < .0001), as well as a greater hepatic content of 18:1 isomers compared to EO-fed mice (P < .001). In EO-fed females, hepatic content of SDA correlated with improved glucose tolerance, as determined by GTT area under the curve (r = −.94; P < 0.01), and in EO-fed males, hepatic content of SDA was positively associated with improved insulin sensitivity (r = .79; P < 0.05). In BO-fed males, hepatic content of total OCFA was negatively correlated with fasting plasma insulin levels (r = −.83; P < 0.05), and hepatic content of total iso BCFA was associated with improved insulin sensitivity (r = −.89; P < 0.05). Conclusions These findings demonstrate that habitual consumption of unique FA derived from dairy fat and echium oil influences hepatic FA composition and content and correlates with improvements in whole-body glucose homeostasis in an aged population. Furthermore, this study suggests that dietary fat quality may be part of an effective preventative strategy for metabolic diseases such as T2D in the elderly. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1006628).

scholarly journals SUN-670 P300 and CBP Are Necessary for Skeletal Muscle Insulin-Stimulated Glucose Uptake

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Vitor Fernandes Martins ◽  
Samuel LaBarge ◽  
Kristoffer Svensson ◽  
Jennifer M Cunliffe ◽  
Dion Banoian ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Binding Protein ◽  
Whole Body ◽  
Oral Glucose ◽  
Skeletal Muscle Insulin Sensitivity

Abstract Introduction: Akt is a critical mediator of insulin-stimulated glucose uptake in skeletal muscle. The acetyltransferases, E1A binding protein p300 (p300) and cAMP response element-binding protein binding protein (CBP) are phosphorylated and activated by Akt, and p300/CBP can acetylate and inactivate Akt, thus giving rise to a possible Akt-p300/CBP axis. Our objective was to determine the importance of p300 and CBP to skeletal muscle insulin sensitivity. Methods: We used Cre-LoxP methodology to generate mice with a tamoxifen-inducible, conditional knock out of Ep300 and/or Crebbp in skeletal muscle. At 13-15 weeks of age, the knockout was induced via oral gavage of tamoxifen and oral glucose tolerance, ex vivo skeletal muscle insulin sensitivity, and microarray and proteomics analysis were done. Results: Loss of both p300 and CBP in adult mouse skeletal muscle rapidly and severely impairs whole body glucose tolerance and skeletal muscle insulin sensitivity. Furthermore, giving back a single allele of either p300 or CBP rescues both phenotypes. Moreover, the severe insulin resistance in the p300/CBP double knockout mice is accompanied by significant changes in both mRNA and protein expression of transcript/protein networks critical for insulin signaling, GLUT4 trafficking, and metabolism. Lastly, in human skeletal muscle samples, p300 and CBP protein levels correlate significantly and negatively with markers of insulin resistance. Conclusions: p300 and CBP are jointly required for maintaining whole body glucose tolerance and insulin sensitivity in skeletal muscle.

scholarly journals Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses

2016 ◽  
Vol 8 (2) ◽  
pp. 206-215 ◽  
Author(s):  
O. A. Valenzuela ◽  
J. K. Jellyman ◽  
V. L. Allen ◽  
N. B. Holdstock ◽  
A. J. Forhead ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Young Adult ◽  
Glucose Tolerance ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Sexually Dimorphic ◽  
Genetic And Environmental Factors ◽  
Glucose Stimulated Insulin Secretion

In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose–insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic–euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose–insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.

scholarly journals Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

2012 ◽  
Vol 302 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
Elizabeth M. Marchionne ◽  
Maggie K. Diamond-Stanic ◽  
Mujalin Prasonnarong ◽  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Renin Inhibition

We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker ( fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser473 phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance.

scholarly journals Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery

2011 ◽  
Vol 300 (5) ◽  
pp. G795-G802 ◽  
Author(s):  
Erik N. Hansen ◽  
Robyn A. Tamboli ◽  
James M. Isbell ◽  
Jabbar Saliba ◽  
Julia P. Dunn ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Whole Body ◽  
Sensitivity Index ◽  
Mixed Meal ◽  
Early Improvement ◽  
Delivery Route ◽  
Over Time

Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB ( P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery ( P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB ( P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time ( P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.

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