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Insulin Resistance and Inflammation.

Evgenii Gusev1, Alexey Sarapultsev1,2, Yulia Zhuravleva1

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Insulin resistance (IR) drives cardiometabolic disease by linking chronic inflammation and cellular stress. This process accelerates vascular injury through self-reinforcing loops between IR and inflammation.

Keywords:
MASLD/NAFLDcellular stressglucose and lipid transportersglucotoxicityinflammationinsulin resistancelipotoxicitymetabolic syndromeobesitytype 2 diabetes

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Area of Science:

  • Cardiovascular Biology
  • Metabolic Disease Research
  • Cellular Stress Response

Background:

  • Insulin resistance (IR) is a key factor in cardiometabolic disease, influencing inflammation and vascular pathology.
  • IR stems from chronic inflammation (meta-inflammation) and cellular stress, leading to endothelial dysfunction and atherogenesis.
  • Understanding the multilevel links between IR, cellular stress, and vascular complications is crucial.

Purpose of the Study:

  • To synthesize the multilevel connections between insulin receptor signaling, intracellular stress pathways, and tissue dysfunction.
  • To propose an integrative framework explaining how chronic stress and inflammation exacerbate IR and vascular injury.
  • To identify convergence points for future mechanistic and translational research.

Main Methods:

  • Conceptual narrative review based on targeted database searches and citation tracking.
  • Distinction between mechanistic/experimental evidence and human observational/interventional data.
  • Framing causal inferences based on mechanistic and interventional findings.

Main Results:

  • Chronic activation of stress-response pathways under nutrient excess and inflammation leads to maladaptive processes.
  • Self-reinforcing loops between IR and inflammation accelerate vascular injury.
  • Identified convergence points for prioritizing research and hypothesis testing.

Conclusions:

  • An integrative framework highlights the interplay between IR, cellular stress, and inflammation in driving cardiometabolic disease.
  • Maladaptive stress responses are central to the progression of IR and vascular pathology.
  • This framework provides a basis for future research into preventing and treating IR-related complications.