Abstract
Development of therapeutic measures to reduce the risk of potentially fatal episodes of hypoglycaemia and thus to achieve the full benefits of intensive insulin therapy in diabetic patients requires a complete understanding of the multifactorial mechanisms for repeated hypoglycaemia-induced blunting of the sympatho-adrenal response (BSAR). After critical analysis of the hypotheses, this review paper suggests a heuristic theory. This theory suggests two mechanisms for the BSAR, each involving a critical role for the central brain noradrenergic system. Furthermore, this theory also suggests that the lateral hypothalamus (LH) plays an important role in this phenomenon. Within the framework of this theory, explanations for 1) sexual dimorphism in the adrenomedullary response (AR), 2) dissociation in the blunting of the AR and the sympathetic response (SR) and 3) antecedent exercise-induced blunting of the AR are provided. In addition, habituation of orexin-A neurons is suggested to cause defective awakening. Moreover, potential therapeutics measures have been also suggested that will reduce or prevent severe episodes of hypoglycaemia.
Keywords: Hypoglycaemia unawareness, Insulin therapy, Defective arousal, Glucose-sensing, Brain glycogen, Noradrenaline
Current Diabetes Reviews
Title: Mechanisms of the Blunting of the Sympatho-Adrenal Response: A Theory
Volume: 5 Issue: 2
Author(s): B. Parekh
Affiliation:
Keywords: Hypoglycaemia unawareness, Insulin therapy, Defective arousal, Glucose-sensing, Brain glycogen, Noradrenaline
Abstract: Development of therapeutic measures to reduce the risk of potentially fatal episodes of hypoglycaemia and thus to achieve the full benefits of intensive insulin therapy in diabetic patients requires a complete understanding of the multifactorial mechanisms for repeated hypoglycaemia-induced blunting of the sympatho-adrenal response (BSAR). After critical analysis of the hypotheses, this review paper suggests a heuristic theory. This theory suggests two mechanisms for the BSAR, each involving a critical role for the central brain noradrenergic system. Furthermore, this theory also suggests that the lateral hypothalamus (LH) plays an important role in this phenomenon. Within the framework of this theory, explanations for 1) sexual dimorphism in the adrenomedullary response (AR), 2) dissociation in the blunting of the AR and the sympathetic response (SR) and 3) antecedent exercise-induced blunting of the AR are provided. In addition, habituation of orexin-A neurons is suggested to cause defective awakening. Moreover, potential therapeutics measures have been also suggested that will reduce or prevent severe episodes of hypoglycaemia.
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Cite this article as:
Parekh B., Mechanisms of the Blunting of the Sympatho-Adrenal Response: A Theory, Current Diabetes Reviews 2009; 5 (2) . https://dx.doi.org/10.2174/157339909788166846
DOI https://dx.doi.org/10.2174/157339909788166846 |
Print ISSN 1573-3998 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6417 |
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