Search for the Hypoglycemia Receptor Using the Local Irrigation Approach
The central nervous system (CNS) has been implicated in glucose homeostasis since Claude Bernard’s1 observation in the mid-19th century that puncture of the fourth ventricle of the brain resulted in glycosuria. Observations in the early part of this century that specific lesions in the hypothalamus were associated with hyperglycemia and glycosuria, provided added support for a role of the CNS in glucose metabolism. 2,3 Extensive research has subsequently revealed that the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) are capable of exerting reciprocal control over glucose metabolism.4–6 Electrical stimulation of the VMH leads to hyperglycemia, hepatic glycogenosis, hyperglucagonemia, and hyppinsulinemia. 7,8 Conversely, lesions to the VMH are characterized by hyperinsulinemia. 4,5 Chemical stimulation of the LH with epinephrine or norepinephrine leads to elevated secretion of insulin. 9 A similar insulin response has been observed with electrical stimulation of the dorsal motor nucleus of the vagus, with which the LH interacts. It has been further shown that the VMH and LH are capable of direct effects upon hepatic glycogenosis, gluconeogenesis and glycogenesis. Stimulation of the VMH activates glycogen phosphorylase and Dhosphoenolpyruvate carboxykinase (PEPCK), while reducing pyruvate kinase activity. 10,11 Alternatively, stimulation of the LH leads to activation of glycogen synthetase and suppression of PEPCK activity. 10,11 Thus the VMH and LH have the potential to exert a strong control over hepatic glycogen metabolism via direct hepatic innervation and innervation of endocrine glands.
KeywordsBlood Glucose Concentration Insulin Infusion Lateral Hypothalamus Glucagon Response Hypoglycemic Unawareness
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