The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin-linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycemia and insulinemia concurrently with a reduction of the expression and membrane presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wild-type littermates (WT). Tolerance tests and insulin sensitivity indexes confirmed the insulin resistance in cKD-ILK, suggesting a similar stage to prediabetes in humans. Under randomly fed conditions, no differences between cKD-ILK and WT were observed in the expression of insulin receptor (IR-B) and its substrate IRS-1 expressions. The IR-B isoform phosphorylated at tyrosines 1150/1151 was increased, but the AKT phosphorylation in serine 473 was reduced in cKD-ILK tissues. Similarly, ILK-blocked myotubes reduced their GLUT4 promoter activity and GLUT4 expression levels. On the other hand, the glucose uptake capacity in response to exogenous insulin was impaired when ILK was blocked and , although IR/IRS/AKT phosphorylation states were increased but not different between groups. We conclude that ILK depletion modifies the transcription of GLUT4, which results in reduced peripheral insulin sensitivity and glucose uptake, suggesting ILK as a molecular target and a prognostic biomarker of insulin resistance.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1530/JOE-16-0662 | DOI Listing |
Background/objectives: Obesity is associated with numerous metabolic complications including insulin resistance, dyslipidemia, and a reduced capacity for physical activity. Whole-body ablation of liver fatty acid-binding protein (LFABP) in mice was shown to alleviate several of these metabolic complications; high fat (HF) fed LFABP knockout (LFABP ) mice developed higher fat mass than their wild-type (WT) counterparts but displayed a metabolically healthy obese (MHO) phenotype with normoglycemia, normoinsulinemia, and reduced hepatic steatosis compared with WT. LFABP is expressed in both liver and intestine, thus in the present study, LFABP conditional knockout (cKO) mice were generated to determine the contributions of LFABP specifically within the liver or the intestine to the whole body phenotype of the global knockout.
View Article and Find Full Text PDFSarcopenia (SP), an age-associated condition marked by muscle weakness and loss has been strongly connected with metabolic factors according to substantial evidence. Nevertheless, the causal correlation between SP and serum metabolites, and the biological signaling pathways involved, is still not well understood. We performed a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal relationships between 1091 levels and 309 ratios of metabolites with SP traits, alongside investigating the relevant biological signaling pathways.
View Article and Find Full Text PDFFood Sci Nutr
January 2025
Department of Horticulture and Food Security JKUAT Nairobi Kenya.
Microgreens of Brassica plants have attracted increasing research interest in the management of the prevailing epidemic of Type 2 diabetes mellitus (T2DM) because of their high nutritional value. This study evaluated the antidiabetic effects of Microgreens Ethanolic Extract (BMEE) in type-2 diabetic rats. For the normoglycemic assay, rats were divided into five groups and received a single oral dose of 100, 250, and 500 mg/kg of BMEE while the control groups received distilled water and Glibenclamide.
View Article and Find Full Text PDFCureus
December 2024
Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, JPN.
The purpose of this study is to examine the pregestational BMI value that results in insulin use in Japanese patients with gestational diabetes mellitus (GDM) and to assess whether the type of GDM treatment affects postpartum glucose tolerance. This retrospective study included 21 GDM patients treated until parturition at our department from 2013 to 2017. We calculated the pregestational BMI related to insulin treatment and the significant elevation in homeostasis model assessment of insulin resistance (HOMA-IR) by receiver operating characteristics curve (ROC) analysis.
View Article and Find Full Text PDFCureus
December 2024
Department of Medical Affairs, Eris Lifesciences Ltd., Ahmedabad, IND.
Background Polycystic ovary syndrome (PCOS) poses a significant health concern among reproductive-aged women and is characterized by ovarian dysfunction, hyperandrogenism, and insulin resistance. This study aims to assess the efficacy and safety of metformin and myo-inositol combination therapy compared to metformin monotherapy in patients with PCOS. Materials and methods This was a phase III, double-blind, randomized controlled clinical trial.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!