Internal Hyperglycemia Unawareness: A Neuroendocrine Hypothesis of Central Glucose Sensor Adaptation and Persistent Hepatic Gluconeogenesis

This record presents a hypothesis proposing the concept of Internal Hyperglycemia Unawareness. The model suggests that chronic hyperglycemia may induce adaptive desensitization of hypothalamic glucose-sensing mechanisms, resulting in persistent hepatic gluconeogenesis despite elevated blood glucose levels. A schematic diagram illustrating the proposed neuroendocrine brain–liver regulatory pathway and the potential role of vasopressin signaling through V1 and V1b receptors is included. The work integrates clinical observations of asymptomatic hyperglycemia with emerging insights into neuroendocrine regulation of glucose metabolism.

Key Words 

• Hyperglycemia
• Neuroendocrine regulation
• Gluconeogenesis
• Hypothalamus
• Vasopressin
• Diabetes physiology
• Brain–liver axis .