Inflammatory Mechanisms in the Regulation of Insulin Resistance

By Herbert Tilg, A. Moschen. Molecular Medicine, 2008

788 citations recorded by the source corpus.

Insulin resistance (IR) plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and nonalcoholic fatty liver disease. It has been demonstrated that IR is associated with a state of chronic low-grade inflammation, and several mediators released from various cell types, including immune cells and adipocytes, have been identified as being involved in the development of IR. Among those are several pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, and various adipocytokines. Furthermore, several transcription factors and kinases such as c-Jun N-terminal kinase (JNK) and inhibitor of kappa B kinase-β (IKKβ), a kinase located proximal of nuclear factor-κB (NF-κB), participate in this process. Hepatocyte-specific overexpression of NF-κB is associated with IR and can mimic all features of fatty liver disease. Whereas the evidence for an important role of many pro-inflammatory pathways in IR in in vitro and animal studies is overwhelming, data from interventional studies in humans to prove this concept are still minor. As a complex network of inflammatory cytokines, adipocytokines, transcription factors, receptor molecules, and acute-phase reactants are involved in the development of IR, new therapeutic approaches in IR-related diseases will be based on a better understanding of their complex interactions.

Subfields: Cancer Research, Cardiology and Cardiovascular Medicine, Epidemiology

View Paper: https://www.semanticscholar.org/paper/aa68bd4d95a85fbb0e1e680551d5f7ebd69725a4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Herbert Tilg
2. A. Moschen

In Cardiology and Cardiovascular Medicine

1. Herbert Tilg
2. A. Moschen

In Epidemiology

1. Herbert Tilg
2. A. Moschen
3. Jamal Naderi
4. M. Longo
5. C. Miele
6. G. A. Raciti
7. F. Beguinot
8. Federica Zatterale

Citations in the corpus

• Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes (2020, background): “Such inflammatory mediators modulate IR either directly by affecting insulin signaling or indirectly by stimulating inflammatory pathways (Tilg and Moschen, 2008).”
• Insulin resistance: Review of the underlying molecular mechanisms (2018, background): “IL‐1 reduces IRS‐1 expression via ERK1/2 and can also activate the IKKβ/NF‐κB pathway in adipocytes and skeletal muscle (Tilg & Moschen, 2008).”
• Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis (2010, background): “Insulin resistance is an important feature of NAFLD and is caused by a variety of factors, including soluble mediators derived from immune cells and/or adipose tissue.(68) Insulin resistance may augment inflammation in NASH because patients with type 2 diabetes mellitus are often worse in terms of h”
• The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives (2018, background): “Type 2 Diabetes Independent of the aetiopathogenetic mechanism among the different types of diabetes, the common pathway seems to be the inflammation in the pancreatic Langerhans beta cell islets (insulitis), in the concept of an auto-inflammatory process, which results in reduction in both beta cel”
• The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis (2017, background): “Inflammatory cytokines produced by the M1 macrophages act on surrounding fat cells and attenuate their sensitivity to insulin [84].”