Insulin resistance and cellular metabolism fundamentals: a review

Nutrient and oxygen uptake are the basis of cellular metabolism. Metabolic demand dynamically controls internal stability, energy harnessing, cellular homeostasis, membrane fluidity, nutrient uptake, signal transduction, intercellular communication, and ultimately, organism survival. Physiological glucose resistance protects cells against glucose overconsumption and oxidative stress but may become pathological in both insulin-independent and insulin-dependent cells. The plasma membrane lipid bilayer, composed of phospholipids with fatty acid tails of varying degrees of unsaturation, contributes to membrane fluidity. Red blood cells (RBCs) are more susceptible to glucose resistance than other cells because they move through extreme environments with low pH and high pressure. Therefore, RBCs are more likely to develop pathological glucose resistance, thereby impairing oxygen transport and increasing dependence on anaerobic glycolysis in other normal tissues. This shift results in lactic acid accumulation, leading to a vicious cycle of metabolic dysfunction and glucose resistance. Moreover, glucose resistance affects the glucose consumption by RBCs, which can lead to elevated blood glucose levels. This hyperglycemia triggers enhanced insulin secretion by beta cells. Insulin upregulates glucose uptake in normal insulin-sensitive cells and stimulates glycogen storage in the liver and muscle. Excess glucose in adipocytes is converted to fat, promoting lipogenesis.