Central Versus Peripheral Glucose Sensing and the Response to Hypoglycemia

Abstract

One of the most significant limits in our ability to tightly control blood glucose in patients with diabetes is the occurrence of hypoglycemia. It is now clear that when blood glucose drops in a normal individual, there is a rapid and well-coordinated endocrine response (1). Glucagon, epinephrine, norepinephrine, cortisol, and growth hormone levels rise as the glucose level falls (1). The combination of low blood glucose and elevated hormones limits glucose utilization by the tissues of the body and stimulates glucose production by the liver (2). As a consequence of these metabolic adjustments, the fall in blood glucose is limited and the ensuing hypoglycemia is minimized. In an individual with diabetes, the glucagon response to hypoglycemia begins to diminish relatively early in the disease process (1). Later, even the sympatho-adrenal response may become limited (1). As a consequence, individuals with diabetes, particularly type 1 diabetes, are at increased risk for serious hypoglycemia. Understanding more about the normal response to hypoglycemia and about the failure of the normal response in diabetic individuals is thus of great importance. A recent debate in this area relates to the site of hypoglycemic sensing. While it has long been known that the brain is involved in detecting low blood glucose, data began to appear in the early 1990s supporting the view that hypoglycemic sensing was also occurring at peripheral sites, particularly within the hepato-portal region. A series of articles by Donovan and …