Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence

Table 1

Cellular pathways linking physical inactivity and insulin resistance (IST = insulin signal transduction).

Molecular mechanisms	Effects of physical inactivity	Experimental evidence	Clinical evidence
Genetic modulations	Modulates expression/function of IST elements	[26]	[18, 19]
Beta cells’ insufficiency	Induces beta cell insufficiency and reduces pancreatic islet mass	[43, 44]	[37, 40–42, 129]
Obesity and dyslipidemia	Reduces energy expenditure toward dyslipidemia and higher risk of obesity which in turn stimulates insulin resistance	—	[50–53]
Mitochondrial dysfunction	Reduces mitochondrial mass, which in turn impairs insulin expression/secretion/signaling	[68]	[19, 67, 69, 70]
Oxidative damages	Increases free radical species followed by more systemic oxidative stress	[76]	[77, 78]
Inflammation	Onset and progress low-grade inflammatory response, which in turn induce insulin resistance	—	[91–93]
Sex steroids	Modulates sex steroid expression/secretion leading to impaired glucose homeostasis	—	[104, 105]
Capillarization	Reduces the amount of vascular network, which in turn impairs insulin sensitivity	—	[106, 112]
Ceramide synthesis	Increases the amount of ceramide synthesis, which in turn interferes with insulin signaling	—	[125–127]