Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study

AbstractWe assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=–0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

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Progression from High Insulin Resistance to Type 2 Diabetes Does Not Entail Additional Visceral Adipose Tissue Inflammation

PLoS ONE ◽

10.1371/journal.pone.0048155 ◽

2012 ◽

Vol 7 (10) ◽

pp. e48155 ◽

Cited By ~ 22

Author(s):

Nuria Barbarroja ◽

Chary Lopez-Pedrera ◽

Lourdes Garrido-Sanchez ◽

Maria Dolores Mayas ◽

Wilfredo Oliva-Olivera ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

High Insulin ◽

Visceral Adipose

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The combination of insulin resistance and visceral adipose tissue estimation improves the performance of metabolic syndrome as a predictor of type 2 diabetes

Diabetic Medicine ◽

10.1111/dme.14274 ◽

2020 ◽

Vol 37 (7) ◽

pp. 1192-1201 ◽

Cited By ~ 2

Author(s):

N. E. Antonio‐Villa ◽

O. Y Bello‐Chavolla ◽

A. Vargas‐Vázquez ◽

R. Mehta ◽

C. A. Aguilar‐Salinas ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Visceral Adipose

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Galectin-3 Deletion Enhances Visceral Adipose Tissue Inflammation and Dysregulates Glucose Metabolism in Mice on a High-Fat Diet

Serbian Journal of Experimental and Clinical Research ◽

10.1515/sjecr-2016-0030 ◽

2016 ◽

Vol 17 (3) ◽

pp. 231-240 ◽

Cited By ~ 1

Author(s):

Ilija Jeftic ◽

Marina Miletic-Kovacevic ◽

Nemanja Jovicic ◽

Jelena Pantic ◽

Nebojsa Arsenijevic ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Glucose Metabolism ◽

Visceral Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Galectin 3 ◽

Visceral Adipose

Abstract Obesity and type 2 diabetes mellitus (T2DM) constitute major health problems worldwide. Increased visceral adiposity enhances the risk of insulin resistance and type 2 diabetes. The mechanisms involved in obesity-associated chronic inflammation in metabolic tissues (metaflammation) that lead to insulin resistance and dysregulated glucose metabolism are incompletely defined. Galectin-3 (Gal-3), a β-galactoside-binding lectin, modulates immune/inflammatory responses and specifically binds to metabolic danger molecules. To dissect the role of Gal-3 in obesity and diabetes, Gal-3-deficient (LGALS3-/-) and wild-type (WT) C57Bl/6 male mice were placed on a high-fat diet (HFD, 60% kcal fat) or a standard chow diet (10% kcal fat) for 6 months and metabolic, histological and immunophenotypical analyses of the visceral adipose tissue were performed. HFD-fed LGALS3-/- mice had higher body weights and more body weight gain, visceral adipose tissue (VAT), hyperglycaemia, hyperinsulinemia, insulin resistance and hyperlipidemia than diet-matched WT mice. Compared to WT mice, the enlarged VAT in obese LGALS3-/- mice contained larger adipocytes. Additionally, we demonstrate enhanced inflammation in the VAT of LGALS3-/- mice compared with diet-matched WT mice. The VAT of LGALS3-/- mice fed a HFD contained more numerous dendritic cells and proinflammatory F4/80+CD11c+CD11b+ and F4/80high macrophages. In contrast to WT mice, the numbers of CXCR3+ and CD8+ T cells were increased in the VAT of Gal-3-deficient mice after 6 months of high-fat feeding. We provide evidence that Gal-3 ablation results in enhanced HFD-induced adiposity, inflammation in the adipose tissue, insulin resistance and hyperglycaemia. Thus, Gal-3 represents an important regulator of obesity-associated immunometabolic alterations.

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Expression of Syntaxin 8 in Visceral Adipose Tissue Is Increased in Obese Patients with Type 2 Diabetes and Related to Markers of Insulin Resistance and Inflammation

Archives of Medical Research ◽

10.1016/j.arcmed.2014.12.003 ◽

2015 ◽

Vol 46 (1) ◽

pp. 47-53 ◽

Cited By ~ 5

Author(s):

Andoni Lancha ◽

Santiago López-Garrido ◽

Amaia Rodríguez ◽

Victoria Catalán ◽

Beatriz Ramírez ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Obese Patients ◽

Visceral Adipose

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Visceral Adipose Tissue as an Indicator of Insulin Resistance in Nonobese Patients with New Onset Type 2 Diabetes Mellitus

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2006-923886 ◽

2006 ◽

Vol 114 (02) ◽

pp. 58-62 ◽

Cited By ~ 16

Author(s):

O. Basat ◽

S. Ucak ◽

H. Ozkurt ◽

M. Basak ◽

S. Seber ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Nonobese Patients ◽

Visceral Adipose ◽

New Onset

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Irisin Is Expressed and Produced by Human Muscle and Adipose Tissue in Association With Obesity and Insulin Resistance

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-2749 ◽

2013 ◽

Vol 98 (4) ◽

pp. E769-E778 ◽

Cited By ~ 395

Author(s):

José María Moreno-Navarrete ◽

Francisco Ortega ◽

Marta Serrano ◽

Ester Guerra ◽

Gerard Pardo ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Human Muscle ◽

Gene Markers ◽

Negatively Associated ◽

Visceral Adipose

Context: Recently irisin (encoded by Fndc5 gene) has been reported to stimulate browning and uncoupling protein 1 expression in sc adipose tissue of mice. Objective: The objective of the study was to investigate FNDC5 gene expression in human muscle and adipose tissue and circulating irisin according to obesity, insulin sensitivity, and type 2 diabetes. Design, Patients, and Main Outcome Measure: Adipose tissue FNDC5 gene expression and circulating irisin (ELISA) were analyzed in 2 different cohorts (n = 125 and n = 76); muscle FNDC5 expression was also evaluated in a subcohort of 34 subjects. In vitro studies in human preadipocytes and adipocytes and in induced browning of 3T3-L1 cells (by means of retinoblastoma 1 silencing) were also performed. Results: In both sc and visceral adipose tissue, FNDC5 gene expression decreased significantly in association with obesity and was positively associated with brown adipose tissue markers, lipogenic, insulin pathway-related, mitochondrial, and alternative macrophage gene markers and negatively associated with LEP, TNFα, and FSP27 (a known repressor of brown genes). Circulating irisin and irisin levels in adipose tissue were significantly associated with FNDC5 gene expression in adipose tissue. In muscle, the FNDC5 gene was 200-fold more expressed than in adipose tissue, and its expression was associated with body mass index, PGC1α, and other mitochondrial genes. In obese participants, FNDC5 gene expression in muscle was significantly decreased in association with type 2 diabetes. Interestingly, muscle FNDC5 gene expression was significantly associated with FNDC5 and UCP1 gene expression in visceral adipose tissue. In men, circulating irisin levels were negatively associated with obesity and insulin resistance. Irisin was secreted from human adipocytes into the media, and the induction of browning in 3T3-L1 cells led to increased secreted irisin levels. Conclusions: Decreased circulating irisin concentration and FNDC5 gene expression in adipose tissue and muscle from obese and type 2 diabetic subjects suggests a loss of brown-like characteristics and a potential target for therapy.

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