Effects of Alterations in Acid-Base Effects on Insulin Signaling

Abstract

Insulin tightly regulates glucose levels within a narrow range through its action on muscle, adipose tissue and the liver. The activation of insulin receptors activates multiple intracellular pathways with different functions. Another tightly regulated complex system in the body is acid-base balance. Metabolic acidosis, defined as a blood pH < 7.35 and serum bicarbonate < 22 mmol/L, has clear pathophysiologic consequences including an effect on insulin action. With the ongoing intake of typical acid-producing Western diets and the age-related decline in renal function, there is an increase in acid levels within the range considered to be normal. This modest increase in acidosis is referred to as "acid stress" and it may have some pathophysiological consequences. In this article, we discuss the effects of acid stress on insulin actions in different tissues.

Keywords: acid stress; growth; hormone; lipolysis; proteolysis; renal function.

Figure 1

Intracellular insulin signaling pathways. Abbreviations: IRS—insulin receptor substrate; PI3K—phosphatidylinositol kinase; PDK3—phosphoinositide-dependent protein kinase 1; Akt—a seronine/threonine kinase, also known as protein kinases B; ChREBP—carbohydrate response element-binding protein; mTOR—mechanistic target of rapamycin; Grb2—growth factor receptor bound protein 2; MEK—mitogen activated protein kinase; MAP kinase—mitogen activated protein kinase.

Figure 2

Effects of insulin and counterregulatory hormones on energy balance.