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Context Increased standing time has been associated with improved health, but the underlying mechanism is unclear. Objectives We herein investigate if increased weight loading increases energy demand and thereby glucose uptake (GU) locally in bone and/or muscle in the lower extremities. Methods In this single-center clinical trial with a randomized crossover design (ClinicalTrials.gov ID, NCT05443620), we enrolled 10 men with body mass index between 30 and 35 kg/m2. Participants were treated with both high load (standing with weight vest weighing 11% of body weight) and no load (sitting) on the lower extremities. GU was measured using whole-body quantitative positron emission tomography/computed tomography imaging. The primary endpoint was the change in GU ratio between loaded bones (ie, femur and tibia) and nonloaded bones (ie, humerus). Results High load increased the GU ratio between lower and upper extremities in cortical diaphyseal bone (eg, femur/humerus ratio increased by 19%, P =.029), muscles (eg, m. quadriceps femoris/m. triceps brachii ratio increased by 28%, P =.014), and certain bone marrow regions (femur/humerus diaphyseal bone marrow region ratio increased by 17%, P =.041). Unexpectedly, we observed the highest GU in the bone marrow region of vertebral bodies, but its GU was not affected by high load. Conclusion Increased weight-bearing loading enhances GU in muscles, cortical bone, and bone marrow of the exposed lower extremities. This could be interpreted as increased local energy demand in bone and muscle caused by increased loading. The physiological importance of the increased local GU by static loading remains to be determined. [ABSTRACT FROM AUTHOR]

This article explores the relationship between insulin hypersecretion and impaired insulin action on glucose metabolism. It presents two competing hypotheses regarding the role of insulin hypersecretion in promoting obesity and insulin resistance. The study conducted by Tricò et al. focuses on individuals with insulin hypersecretion and finds that they have higher rates of de novo lipogenesis and increased adipose tissue. The article also discusses the limitations of current methods used to assess insulin sensitivity and highlights the complexity of glucose homeostasis. Overall, this research provides important insights into the regulation of plasma glucose concentration and raises questions about the traditional understanding of the relationship between insulin sensitivity, insulin secretion, and plasma glucose levels. Further research is needed to better understand the mechanisms underlying insulin hypersecretion and its impact on metabolic health. [Extracted from the article]

Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where the pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells. We examined the relationship between GAL-1 and soluble immune markers and T-cell subsets in a cohort of children with T1D and/or CeD relative to healthy children. GAL-1, together with several soluble immune markers [e.g. interleukins (IL)], tumor necrosis factor (TNF), acute phase proteins, and matrix metalloproteinases (MMP) were measured in sera from children with T1D and/or CeD by fluorochrome (Luminex) technique using children without these diseases as a reference. Subgroups of T cells, including T-regulatory (Treg) cells, were analysed by flow cytometry. Association between GAL-1, pro-inflammatory markers, and Treg cells differed depending on which illness combination was present. In children with both T1D and CeD, GAL-1 correlated positively with pro-inflammatory markers (IL-1β, IL-6, and TNF-α). Composite scores increased the strength of correlation between GAL-1 and pro-inflammatory markers, Th1-associated interferon (IFN)-γ, and T1D-associated visfatin. Contrary, in children diagnosed with exclusively T1D, GAL-1 was positively correlated to CD25hi and CD25hiCD101+ Treg cells. For children with only CeD, no association between GAL-1 and other immune markers was observed. In conclusion, the association observed between GAL-1, soluble immune markers, and Treg cells may indicate a role for GAL-1 in the pathophysiology of T1D and, to some extent, also in CeD. Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells and the association observed between GAL-1, soluble immune markers, and T regulatory (Treg) cells may indicate a role for GAL-1 in the pathophysiology of children with T1D and, to some extent, also in children with CeD. Graphical Abstract [ABSTRACT FROM AUTHOR]

The article "Response to Comment on Mittendorfer et al. Insulin Hypersecretion as Promoter of Body Fat Gain and Hyperglycemia" discusses the complexities of insulin signaling and insulin resistance. It highlights the role of spare receptors in achieving a maximal response to insulin, even when the number of insulin receptors on the cell surface is low. The text emphasizes that spare receptors do not protect against impaired insulin sensitivity, which is commonly observed in obesity. The authors, Bettina Mittendorfer, James D. Johnson, Giovanni Solinas, and Per-Anders Jansson, provide insights into the mechanisms of insulin resistance and the importance of understanding insulin signaling in metabolic disorders. [Extracted from the article]

Adipose tissue (AT) had emerged as an endocrine organ and a key regulator of the metabolically triggered inflammation. The aims of this study were 1) to investigate the usefulness of a multiplexed bioassay in characterizing a panel of adipokines in subcutaneous (sc) microdialysate samples and 2) to determine whether lean and obese individuals differ in their interstitial adipokines levels following microdialysis (MD) probe insertion. Ultrafiltrating MD membranes were inserted in opposite sites of the sc abdominal AT of six lean (L) and six obese (OB) males at the beginning (M1) and during the last 120 rain (M2) of the study. Interstitial and serum concentrations of adipokines were quantified using the Luminex technique and ELISA at 60-rain intervals for 5 h. In comparison with L subjects, OB subjects exhibited elevated interstitial leptin (P < 0.001), IL-8 (P < 0.05), and IL-18 levels (P = 0.05), as well as higher serum concentrations of leptin (P < 0.0001), IL-6 (P < 0.0001), tumor necrosis factor-[alpha] (P < 0.001), IL-8 (P = 0.01) and interferon-[gamma]-inducible protein 10 (P < 0.05). In samples from the M1 membranes, leptin decreased and IL-1[alpha], IL-18, and RANTES (regulated on activation, normal T-cell expressed and secreted) remained relatively stable, whereas IL-6, IL-8, and monocyte chemoattractant protein-1 significantly increased after the first hour (P < 0.0001 vs. baseline). Notably, either the magnitude of increase from the initial values or the time pattern of all the adipokines in M 1 and M2 dialysates were similar between the groups. In conclusion, the current work provides valuable information on the optimal time frame to collect in situ AT microdialysate samples. Further studies are needed, however, to unravel the intricate interplay of cytokines in AT interstitial fluid. adipose tissue; inflammation; subcutaneous microdialysis

A study was conducted to determine the serum levels of retinol-binding protein 4, a molecule secreted by adipocytes, correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Levels of adipocytes secreted molecule appear to be elevated in serum before the development of frank diabetes and might be used to identify insulin resistance and associated cardiovascular risk factors.