Beta-adrenergic blockade inhibits thermogenesis and lipolysis during glucoprivation in humans

Glucoprivic stress induced by 2-DG (2-deoxy-D-glucose) is associated with increased oxygen consumption (thermogenesis) and sympathetic nervous system activity, as well as elevations of circulating levels of various hormones and metabolic substrates. To examine the role of beta-adrenergic stimulation in the thermogenic, hyperglycemic, and lipolytic responses to glucoprivation, we administered intravenous infusions of propranolol or normal saline (placebo) during 2-DG challenges in seven healthy males. 2-DG alone produced large increments in plasma catecholamine levels, hyperglycemia, a 3.5-fold increase in plasma free fatty acid (FFA) levels, a 15 beat/min increase in pulse rate, and hypothermia in spite of a 20% increase in oxygen consumption. When propranolol was given, 2-DG produced only a 50% increase in FFA levels, no change in oxygen consumption, and a 17 beat/min fall in pulse rate associated with a 25% increase in mean arterial blood pressure. Propranolol only slightly attenuated the hyperglycemia and hypothermia associated with 2-DG but potentiated the elevations of plasma epinephrine levels. It is concluded that 2-DG-induced thermogenesis and lipolysis are primarily dependent on beta-adrenergic stimulation.