Effects of Amino Acids on Glucose Disposal

Free fatty acids are known to inhibit carbohydrate disposal and oxidation. This action may play an important role in the pathophysiology of insulin resistance and non-insulin-dependent diabetes mellitus. To investigate whether amino acids (AAs) have similar actions, we determined the effects of an intravenously infused mixture of 15 AAs on carbohydrate disposal during euglycemichyperinsulinemic clamps associated with either basal or high glucagon concentrations in healthy male volunteers. Plasma glucose concentration was clamped at ∼4.7 mM (coefficient of variation 4.7%). Insulin infusion (7.18 pmol · kg⁻¹ · min⁻¹) raised serum insulin concentrations from 36–50 pM to between 300 and 600 pM. AA infusions (0.5 g · kg⁻¹ h⁻¹ · 4 h) raised plasma α-amino N₂ concentrations about five- to six-fold. Infusion of AAs, somatostatin (somatotropin release inhibitory factor, SRIF), and high-glucagon replacement (3.0 ng · kg⁻¹ · min⁻¹) reduced the rate of exogenous glucose infusion needed to maintain euglycemia from 51.1 ± 7.2 μmol · kg⁻¹ · min⁻¹ (saline + SRIF + high glucagon) to 28.3 ±11.1 μmol · kg⁻¹ · min⁻¹ and stimulated endogenous glucose production (from 0 to ∼17 μmol · kg⁻¹ · min⁻¹). Thus, glucose disposal (exogenous infusion plus endogenous production of glucose) remained essentially unchanged. During infusion of AAs + SRIF + basal glucagon replacement (0.25 ng · kg⁻¹ · min⁻¹), endogenous glucose production remained completely suppressed, and the rates of exogenous glucose infusion did not change (compared with saline + SRIF + basal glucagon replacement). The data showed that 1) hyperaminoacidemia associated with hyperglucagonemia stimulated endogenous glucose production despite hyperinsulinemia, and 2) intravenous infusion of a mixture of 15 AAs had no inhibitory effect on insulin-stimulated total-body glucose disposal.