Many factors impact the fluctuating rates of glucose flux and clearance in one's daily life (meal size and composition, gastric emptying rate, physical activity, etc.). With this constantly changing need for circulating insulin abundance, it is challenging for the treatment strategy to be entirely successful in individuals with type 1 diabetes (T1D), and transient periods of hypoglycemia occur. Humans have evolved metabolic strategies to cope with hypoglycemia, and these include counter-regulatory endocrine responses to increase hepatic glucose production as well as selection of alternative fuels for mitochondrial respiration. The central nervous system can use glycolytic end products that were produced by other tissues (circulating lactate) as well as ketones to some extent. The ability to take up and oxidize these alternative fuels is likely critical for tolerance of and survival through hypoglycemia.
展开▼
