scholarly journals Four‑Stage Evolution of Diabetes or Whole Body Insulin Resistance (WBIR): Debunking of the Lipid‑Induced Insulin Resistance (LIIR) and Proposing of the Glycation‑Induced Insulin Resistance (GIIR)

2019 ◽  
Author(s):  
Song Jae Lee ◽  
Sang Won Shin
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Hepatic Insulin Resistance ◽  
Whole Body ◽  
Rapid Weight Loss ◽  
Global Parameter ◽  
Tissue Specific ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Even though it has long been known that diabetes develops in distinctive stages over a long span of time, no comprehensive diabetes development model has been developed yet. Insulin resistance (IR) plays a major role in development of diabetes. A widespread belief regarding IR is that it is a global parameter affecting the whole body simultaneously by merely impairing glucose uptake in tissues. However, investigation by a new methodology that we have named integrated approach suggests that IR not merely impairs glucose uptake in tissues but also produces tissue‑specific metabolic disruptions varying widely from tissue to tissue, and that IR would not necessarily develop simultaneously over the whole body but instead develop first preferentially in the muscle tissue with a relatively low cell turnover and then progresses in sequence to the subcutaneous adipose tissue to the visceral adipose tissue to the liver with higher cell turnovers. This is the most important rationale for subdividing IR into the four distinct tissue‑specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s‑AIR), visceral adipose insulin resistance (v‑AIR), and hepatic insulin resistance (HIR). Sequential development of tissue‑specific IRs, in the order of MIR, s‑AIR, v‑AIR, and HIR, producing tissue‑specific metabolic disruptions is nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin‑resistant stages. Four‑stage evolution from rapid weight gain to visceral obesity to rapid weight loss to full‑blown diabetic state not only complies well with the natural development history of diabetes, but also resolves most of controversies on diabetes or obesity. Development of the four‑stage WBIR evolution model, which also refutes the entrenched notion of the lipid‑induced insulin resistance (LIIR) but instead supports the glycation‑induced insulin resistance (GIIR) proposed in this study, may possibly be considered a breakthrough in study of diabetes or obesity.

scholarly journals Four‑Stage Evolution of Diabetes or Whole Body Insulin Resistance (WBIR): Debunking of the Lipid‑Induced Insulin Resistance (LIIR) and Proposing of the Glycation‑Induced Insulin Resistance (GIIR)

2019 ◽  
Author(s):  
Song Jae Lee ◽  
Sang Won Shin
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Hepatic Insulin Resistance ◽  
Whole Body ◽  
Rapid Weight Loss ◽  
Global Parameter ◽  
Tissue Specific ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Even though it has long been known that diabetes develops in distinctive stages over a long span of time, no comprehensive diabetes development model has been developed yet. Insulin resistance (IR) plays a central role in development of diabetes. A widespread belief regarding IR is that it is a global parameter affecting the whole body simultaneously by impairing merely glucose uptake in tissues. However, the analysis by a new methodology that we have named integrated approach suggests that IR not merely impairs glucose uptake in tissues but also produces tissue-specific metabolic disruptions varying widely from tissue to tissue, and that IR would not necessarily develop simultaneously over the whole body but instead develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue to the visceral adipose tissue to the liver with higher cell turnovers. This is the most important rationale for subdividing IR into four distinct tissue-specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Sequential development of tissue-specific IRs, in the order of MIR, s-AIR, v-AIR, and HIR, producing tissue-specific metabolic disruptions, is nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin-resistant stages. Four-stage evolution from rapid weight gain to visceral obesity to rapid weight loss to full-blown diabetic state not only complies well with the natural development history of diabetes, but also resolves most of controversies on diabetes or obesity. Development of the four-stage WBIR evolution model, which also refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but instead supports the glycation-induced insulin resistance (GIIR) proposed in this study, may possibly be considered a breakthrough in study of diabetes as well as obesity.

Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Strongly Predict Whole-Body Insulin Resistance in the Development of Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1790-P ◽  
Author(s):  
GRETHA J. BOERSMA ◽  
KERSTIN HEURLING ◽  
MARIA J. PEREIRA ◽  
EMIL JOHANSSON ◽  
MARK LUBBERINK ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Visceral Adipose Tissue ◽  
Whole Body ◽  
Visceral Adipose

scholarly journals Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People with Obesity

2021 ◽  
Author(s):  
Han-Chow E. Koh ◽  
Stephan van Vliet ◽  
Terri A. Pietka ◽  
Gretchen A. Meyer ◽  
Babak Razani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Plasma Fatty Acid ◽  
Insulin Resistant ◽  
High Insulin ◽  
Subcutaneous Adipose

We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [<sup>18</sup>F]fluorodeoxyglucose and [<sup>15</sup>O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin-sensitive, and ii) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin-resistant but not in those who are insulin-sensitive. We found high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT, but was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest several putative SAT factors that are commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.

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

2018 ◽  
Vol 50 (08) ◽  
pp. 627-639 ◽  
Author(s):  
Gretha Boersma ◽  
Emil Johansson ◽  
Maria Pereira ◽  
Kerstin Heurling ◽  
Stanko Skrtic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Visceral Adipose Tissue ◽  
Whole Body ◽  
Control Subjects ◽  
Visceral Adipose

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.

Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People with Obesity

2021 ◽  
Author(s):  
Han-Chow E. Koh ◽  
Stephan van Vliet ◽  
Terri A. Pietka ◽  
Gretchen A. Meyer ◽  
Babak Razani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Plasma Fatty Acid ◽  
Insulin Resistant ◽  
High Insulin ◽  
Subcutaneous Adipose

We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [<sup>18</sup>F]fluorodeoxyglucose and [<sup>15</sup>O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin-sensitive, and ii) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin-resistant but not in those who are insulin-sensitive. We found high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT, but was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest several putative SAT factors that are commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.

Inflammation and impaired adipogenesis in hypertrophic obesity in man

2009 ◽  
Vol 297 (5) ◽  
pp. E999-E1003 ◽  
Author(s):  
Birgit Gustafson ◽  
Silvia Gogg ◽  
Shahram Hedjazifar ◽  
Lachmi Jenndahl ◽  
Ann Hammarstedt ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Preadipocyte Differentiation ◽  
Metabolic Complications ◽  
Adipose Cell ◽  
Subcutaneous Adipose ◽  
Adipose Cell Size

Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNFα, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

1992 ◽  
Vol 263 (5) ◽  
pp. E850-E855 ◽  
Author(s):  
L. Simonsen ◽  
J. Bulow ◽  
J. Madsen ◽  
N. J. Christensen
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Epinephrine Infusion ◽  
Basal Period ◽  
Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

scholarly journals Collagen 24 α1 Is Increased in Insulin-Resistant Skeletal Muscle and Adipose Tissue

2020 ◽  
Vol 21 (16) ◽  
pp. 5738
Author(s):  
Xiong Weng ◽  
De Lin ◽  
Jeffrey T. J. Huang ◽  
Roland H. Stimson ◽  
David H. Wasserman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Resistant ◽  
Global View ◽  
Novel Association ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Aberrant extracellular matrix (ECM) remodelling in muscle, liver and adipose tissue is a key characteristic of obesity and insulin resistance. Despite its emerging importance, the effective ECM targets remain largely undefined due to limitations of current approaches. Here, we developed a novel ECM-specific mass spectrometry-based proteomics technique to characterise the global view of the ECM changes in the skeletal muscle and liver of mice after high fat (HF) diet feeding. We identified distinct signatures of HF-induced protein changes between skeletal muscle and liver where the ECM remodelling was more prominent in the muscle than liver. In particular, most muscle collagen isoforms were increased by HF diet feeding whereas the liver collagens were differentially but moderately affected highlighting a different role of the ECM remodelling in different tissues of obesity. Moreover, we identified a novel association between collagen 24α1 and insulin resistance in the skeletal muscle. Using quantitative gene expression analysis, we extended this association to the white adipose tissue. Importantly, collagen 24α1 mRNA was increased in the visceral adipose tissue, but not the subcutaneous adipose tissue of obese diabetic subjects compared to lean controls, implying a potential pathogenic role of collagen 24α1 in obesity and type 2 diabetes.

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