Until now, catecholamines were the drugs of choice to treat hypotension during shock states. Catecholamines, however, also have marked metabolic effects, particularly on glucose metabolism, and the degree of this metabolic response is directly related to the beta2-adrenoceptor activity of the individual compound used. Under physiologic conditions, infusing catecholamine is associated with enhanced rates of aerobic glycolysis (resulting in adenosine triphosphate production), glucose release (both from glycogenolysis and gluconeogenesis), and inhibition of insulin-mediated glycogenesis. Consequently, hyperglycemia and hyperlactatemia are the hallmarks of this metabolic response. Under pathophysiologic conditions, the metabolic effects of catecholamines are less predictable because of changes in receptor affinity and density and in drug kinetics and the metabolic capacity of the major gluconeogenic organs, both resulting from the disease per se and the ongoing treatment. It is also well-established that shock states are characterized by a hypermetabolic condition with insulin resistance and increased oxygen demands, which coincide with both compromised tissue microcirculatory perfusion and mitochondrial dysfunction. This, in turn, causes impaired glucose utilization and may lead to inadequate glucose supply and, ultimately, metabolic failure. Based on the landmark studies on intensive insulin use, a crucial role is currently attributed to glucose homeostasis. This article reviews the effects of the various catecholamines on glucose utilization, both under physiologic conditions, as well as during shock states. Because, to date (to our knowledge), no patient data are available, results from relevant animal experiments are discussed. In addition, potential strategies are outlined to influence the catecholamine-induced effects on glucose homeostasis.

Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

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