scholarly journals Enhancing Exercise Responsiveness across Prediabetes Phenotypes by Targeting Insulin Sensitivity with Nutrition

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Julian M. Gaitan ◽  
Arthur Weltman ◽  
Steven K. Malin
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Clinical Pathology ◽  
Nutrition Therapy ◽  
The Novel ◽  
Carbohydrate Composition ◽  
Whole Grain ◽  
Hepatic Insulin Sensitivity ◽  
Low Glycemic Index

Exercise is a cornerstone therapy for chronic diseases related to multiorgan insulin resistance. However, not all individuals show the anticipated improvement in insulin sensitivity following exercise and these individuals are considered exercise resistant. Caloric restriction is an approach to enhance the effect of exercise on increasing peripheral and hepatic insulin sensitivity, as replenishing expended calories blunts these benefits. Alternatively, restricting carbohydrate intake, independent of energy balance, following exercise provides an additive effect on peripheral insulin sensitivity when compared to refeeding carbohydrate. Although carbohydrate composition modulates insulin sensitivity, few have studied effects of low glycemic index or whole-grain diets following exercise across prediabetes phenotypes on insulin sensitivity. Herein, we propose the novel hypothesis that the combination of individualized nutrition therapy and exercise should be based on the clinical pathology of prediabetes to overcome exercise resistance and improve responsiveness in people at risk for type 2 diabetes and cardiovascular disease.

Starch and β-glucan in a whole-grain-like structural form improve hepatic insulin sensitivity in diet-induced obese mice

2019 ◽  
Vol 10 (8) ◽  
pp. 5091-5101 ◽  
Author(s):  
Kaiyun Luo ◽  
Xufeng Wang ◽  
Genyi Zhang
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Hepatic Insulin Resistance ◽  
Obese Mice ◽  
Structural Form ◽  
Whole Grain ◽  
Hepatic Insulin Sensitivity

WGLSF improves hepatic insulin resistance and glucose homeostasis in diet-induced obese mice.

scholarly journals Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tina Schumann ◽  
Jörg König ◽  
Christian von Loeffelholz ◽  
Daniel F. Vatner ◽  
Dongyan Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Mitochondrial Respiration ◽  
Lipid Accumulation ◽  
Genome Wide Association Studies ◽  
Alcoholic Fatty Liver ◽  
Hepatic Insulin Sensitivity ◽  
Hepatic Lipid

AbstractGenome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

Long-Term Oral L-Arginine Administration Improves Peripheral and Hepatic Insulin Sensitivity in Type 2 Diabetic Patients

Diabetes Care ◽  
2001 ◽  
Vol 24 (5) ◽  
pp. 875-880 ◽  
Author(s):  
P. Piatti ◽  
L. D. Monti ◽  
G. Valsecchi ◽  
F. Magni ◽  
E. Setola ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Hepatic Insulin Sensitivity ◽  
Type 2 Diabetic

Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

2014 ◽  
Author(s):  
◽  
Leryn J. Boyle
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Physical Inactivity ◽  
Vascular Dysfunction ◽  
Insulin Stimulation

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.

Increasing endogenous PPARγ ligands improves insulin sensitivity and protects against diet-induced obesity without side effects of thiazolidinediones

2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Side Effects ◽  
Knockout Mice ◽  
Fasting Glucose ◽  
Binding Mode ◽  
Fluid Retention ◽  
Diet Induced Obesity

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals Elevated and Correlated Expressions of miR-24, miR-30d, miR-146a, and SFRP-4 in Human Abdominal Adipose Tissue Play a Role in Adiposity and Insulin Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yury O. Nunez Lopez ◽  
Gabriella Garufi ◽  
Magdalena Pasarica ◽  
Attila A. Seyhan
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Linear Models ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Abdominal Adipose Tissue ◽  
Systemic Insulin Resistance ◽  
Novel Association ◽  
Regulatory Loop

Objective. We explored the relationships among microRNAs (miRNAs) and SFRP4, as they relate to adipose tissue functions including lipolysis, glucose and glycerol turnover, and insulin sensitivity. Methods. Abdominal adipose tissue (AbdAT) levels of thirteen microRNAs (miRNAs), SFRP4, and VEGF in lean nondiabetic subjects (n=7), subjects with obesity (n=5), and subjects with obesity and type 2 diabetes (T2DM) (n=5) were measured by qPCR. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp. Osmium fixation and Coulter counting were used for adipocyte sizing. Data were analyzed using generalized linear models that adjusted for age, gender, and ethnicity. Results. AbdAT miR-24, miR-30d, and miR-146a were elevated in subjects with obesity (P<0.05) and T2DM (P<0.1) and positively correlated with measures of percent body fat by DXA (rmiR.24=0.894, rmiR.146a=0.883, P<0.05), and AbdAT SFRP4 (rmiR.30=0.93, rmiR.146a=0.88, P<0.05). These three miRNAs additionally correlated among themselves (rmiR.24~miR.146a=0.90, rmiR.30~miR.146a=0.85, P<0.01). Conclusions. This study suggests a novel association between the elevated levels of miRNAs miR-24, miR-30d, and miR-146a (apparently coregulated) and the level of SFRP4 transcript in AbdAT of subjects with obesity and T2DM. These molecules might be part of a regulatory loop involved in AbdAT remodeling/adiposity and systemic insulin resistance. This trial is registered with NCT00704197.

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