Abstract
There is significant evidence that acute stress, a challenge to an organism's homeostasis, has dramatic effects on metabolic control. Acute stress impairs blood glucose control in people with both type 1 and type 2 diabetes. In addition, growing evidence suggests that metabolic responses to stress in people without diabetes may be a crucial determinant of health. Acute dysregulation of blood glucose in the hospital setting, including both hyper- and hypoglycemia, predicts short- and long-term morbidity and mortality in patients with critical illnesses. Animal studies indicate that exposure to physiological and psychological stressors activates a highly conserved network of neural circuits that ultimately coordinate the functions of multiple organs to increase blood glucose. In this article, we provide an overview of the neural populations and circuits that increase blood glucose in response to acute stress, including our research funded by the American Diabetes Association Pathway to Stop Diabetes program, highlighting the impacts on clinical outcomes and opportunities for the development of therapies for diabetes. This article is part of a series of perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program. ARTICLE HIGHLIGHTS: Internal and external stressors rapidly increase blood glucose, a highly conserved metabolic response. Multiple stress-modulated neural populations in the brain stem, hypothalamus, and forebrain contribute to regulation of the hypothalamo-pituitary-adrenal axis and sympathetic nervous system to elicit hyperglycemia. Exaggerated or diminished glucose responses to acute stress are associated with increased risk of type 2 diabetes and poor health outcomes. A greater understanding of the neural circuitry contributing to stress hyperglycemia and how these circuits are disrupted has the potential to provide new approaches to improve glycemic control.