scholarly journals Role of anatomical location, cellular phenotype and perfusion of adipose tissue in intermediary metabolism: A narrative review

2022 ◽  
Author(s):  
Stefania Camastra ◽  
Ele Ferrannini
Keyword(s):  
Insulin Resistance ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
Muscle Blood Flow ◽  
Diaphragm Muscle ◽  
Whole Body ◽  
Anatomical Location ◽  
Renal Tubular Cells ◽  
Muscle Tissues

AbstractIt is well-established that adipose tissue accumulation is associated with insulin resistance through multiple mechanisms. One major metabolic link is the classical Randle cycle: enhanced release of free fatty acids (FFA) from hydrolysis of adipose tissue triglycerides impedes insulin-mediated glucose uptake in muscle tissues. Less well studied are the different routes of this communication. First, white adipose tissue depots may be regionally distant from muscle (i.e., gluteal fat and diaphragm muscle) or contiguous to muscle but separated by a fascia (Scarpa’s fascia in the abdomen, fascia lata in the thigh). In this case, released FFA outflow through the venous drainage and merge into arterial plasma to be transported to muscle tissues. Next, cytosolic triglycerides can directly, i.e., within the cell, provide FFA to myocytes (but also pancreatic ß-cells, renal tubular cells, etc.). Finally, adipocyte layers or lumps may be adjacent to, but not anatomically segregated, from muscle, as is typically the case for epicardial fat and cardiomyocytes. As regulation of these three main delivery paths is different, their separate contribution to substrate competition at the whole-body level is uncertain. Another important link between fat and muscle is vascular. In the resting state, blood flow is generally higher in adipose tissue than in muscle. In the insulinized state, fat blood flow is directly related to whole-body insulin resistance whereas muscle blood flow is not; consequently, fractional (i.e., flow-adjusted) glucose uptake is stimulated in muscle but not fat. Thus, reduced blood supply is a major factor for the impairment of in vivo insulin-mediated glucose uptake in both subcutaneous and visceral fat. In contrast, the insulin resistance of glucose uptake in resting skeletal muscle is predominantly a cellular defect.

scholarly journals COMP-angiopoietin-1 enhances skeletal muscle blood flow and insulin sensitivity in mice

2009 ◽  
Vol 297 (2) ◽  
pp. E402-E409 ◽  
Author(s):  
Hoon Ki Sung ◽  
Yong-Woon Kim ◽  
Soo Jeong Choi ◽  
Jong-Yeon Kim ◽  
Kyung Hee Jeune ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Chow Diet ◽  
High Fat ◽  
Angiopoietin 1

To test whether chronic enhanced blood flow alters insulin-stimulated glucose uptake, we measured skeletal muscle glucose uptake in chow-fed and high-fat-fed mice injected with adenovirus containing modified angiopoietin-1, COMP-Ang1, via euglycemic-hyperinsulinemic clamp. Blood flow rates and platelet endothelial cell adhesion molecule-1 positive endothelial cells in the hindlimb skeletal muscle were elevated in COMP-Ang1 compared with control LacZ. Whole body glucose uptake and whole body glycogen/lipid synthesis were elevated in COMP-Ang1 compared with LacZ in chow diet. High-fat diet significantly reduced whole body glucose uptake and whole body glycolysis in LacZ mice, whereas high-fat-fed COMP-Ang1 showed a level of whole body glucose uptake that was comparable with chow-fed LacZ and showed increased glucose uptake compared with high-fat-fed LacZ. Glucose uptake and glycolysis in gastrocnemius muscle of chow-fed COMP-Ang1 were increased compared with chow-fed LacZ. High-fat diet-induced whole body insulin resistance in the LacZ was mostly due to ∼40% decrease in insulin-stimulated glucose uptake in skeletal muscle. In contrast, COMP-Ang1 prevented diet-induced skeletal muscle insulin resistance compared with high-fat-fed LacZ. Akt phosphorylation in skeletal muscle was increased in COMP-Ang1 compared with LacZ in both chow-fed and high-fat-fed groups. These results suggest that increased blood flow by COMP-Ang1 increases insulin-stimulated glucose uptake and prevents high-fat diet-induced insulin resistance in skeletal muscle.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

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.

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

Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

2000 ◽  
Vol 279 (2) ◽  
pp. E376-E385 ◽  
Author(s):  
Bente Stallknecht ◽  
Jens J. Larsen ◽  
Kari J. Mikines ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
...  
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Subcutaneous Adipose Tissue ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Glycerol Concentration ◽  
Adipose Tissue Blood Flow ◽  
Subcutaneous Adipose

Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men [insulin infusion rates: 10,000 ( step I), 20,000 ( step II), and 150,000 ( step III) μU · min−1 · m−2]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle (glucose only). Adipose tissue blood flow was measured by 133Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration difference was increased in T during the clamp but not in S subjects in both adipose tissue and muscle [adipose tissue: step I ( n = 8), 0.48 ± 0.18 mM (T), 0.23 ± 0.11 mM (S); step II ( n = 8), 0.19 ± 0.09 (T), −0.09 ± 0.24 (S); step III( n = 5), 0.47 ± 0.24 (T), 0.06 ± 0.28 (S); (T: P < 0.001, S: P > 0.05); muscle: step I ( n = 4), 1.40 ± 0.46 (T), 0.31 ± 0.21 (S); step II ( n = 4), 1.14 ± 0.54 (T), −0.08 ± 0.14 (S); step III( n = 4), 1.23 ± 0.34 (T), 0.24 ± 0.09 (S); (T: P < 0.01, S: P > 0.05)]. Interstitial glycerol concentration decreased faster in T than in S subjects [half-time: T, 44 ± 9 min ( n = 7); S, 102 ± 23 min ( n = 5); P < 0.05]. In conclusion, training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis in subcutaneous adipose tissue. Insulin per se does not influence subcutaneous adipose tissue blood flow.

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.

Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans

2006 ◽  
Vol 291 (1) ◽  
pp. E108-E114 ◽  
Author(s):  
Rikke Krogh-Madsen ◽  
Peter Plomgaard ◽  
Kirsten Møller ◽  
Bettina Mittendorfer ◽  
Bente K. Pedersen
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Muscle Tissue ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Tnf Α

Inflammation is associated with insulin resistance, and both tumor necrosis factor (TNF)-α and interleukin (IL)-6 may affect glucose uptake. TNF induces insulin resistance, whereas the role of IL-6 is controversial. High plasma levels of IL-18 are associated with insulin resistance in epidemiological studies. We investigated the effects of TNF and IL-6 on IL-18 gene expression in skeletal muscle and adipose tissue. Nine human volunteers underwent three consecutive interventions, receiving an infusion of recombinant human (rh)IL-6, rhTNF, and saline. Insulin sensitivity was assessed by measurement of whole body glucose uptake with the stable isotope tracer method during a euglycemic hyperinsulinemic clamp (20 mU·min−1·kg−1), which was initiated 1 h after the IL-6-TNF-saline infusion. Cytokine responses were measured in plasma, muscle, and fat biopsies. Plasma concentrations of TNF and IL-6 increased 10- and 38-fold, respectively, during the cytokine infusions. Whole body insulin-mediated glucose uptake was significantly reduced during TNF infusion but remained unchanged during IL-6 infusion. TNF induced IL-18 gene expression in muscle tissue, but not in adipose tissue, whereas IL-6 infusion had no effect on IL-18 gene expression in either tissue. We conclude that TNF-induced insulin resistance of whole body glucose uptake is associated with increased IL-18 gene expression in muscle tissue, indicating that TNF and IL-18 interact, and both may have important regulatory roles in the pathogenesis of insulin resistance.

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.

Sign in / Sign up

Export Citation Format

Share Document