Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
C. Bernard, Chiens rendus diabetiques, Comot. Rend. Soc. Biol. 1:60 (1849).
E. Sachs and M.E. MacDonald, Blood sugar studies in experimental pituitary and hypothalamic lesions, Arch. Neurol. Psvchiat. 13:335 (1925).
L.O. Morgan and C.A. Johnson, Experimental lesions in the tuber cinereum of the dog, Arch. Neurol. Psvchiat. 24:696 (1930).
C.A. Benzo, The hypothalamus and blood glucose regulation, Life Sci. 32:2509 (1983).
T. Shimazu, Neuronal regulation of hepatic glucose metabolism in mammals, Diabetes Metab. Rev. 3:185 (1987).
T. Shimazu, A. Fukuda, and T. Ban, Reciprocal influences of the ventromedial and lateral hypothalamic nuclei on blood glucose level and liver glycogen content, Nature 210:1178 (1966).
L.A. Frohman and L.L. Bernardis, Effect of hypothalamic stimulation on plasma glucose, insulin and glucagon levels, Am. J. Physiol. 221:1596 (1971).
S.C. Woods and D. Porte, Jr, Neural control of the endocrine pancreas, Physiol. Rev. 54:596 (1974).
T. Shimazu and K. Ishikawa, Modulation by the hypothalamus of glucagon and insulin secretion in rabbits: studies with electrical and chemical stimulations, Endocrinol. 108:605 (1981).
T. Shimazu, H. Matsushita, and K. Ishikawa, Hypothalamic control of liver glycogen metabolism in adult and aged rats, Brain Res. 144:343 (1978).
T. Shimazu and S. Ogasawara, Effect of hypothalamic stimulation on gluconeogenesis and glycolysis in rat liver, Am. J. Physiol. 228:1787 (1975).
W.B. Cannon, M.A. Mclver, and S.W. Bliss, Studies on the conditions of activity in endocrine glands. XIII. A sympathetic and adrenal mechanism for mobilizing sugar in hypoglycemia, Am. J. Physiol. 69:46 (1924).
R.R. Miselis and A.N. Epstein, Feeding induced by intracerebroventricular 2-deoxyglucose in the rat, Am. J. Phvsiol. 229:1438 (1975).
Y. Oomura, Glucose as a regulator of neuronal activity, in: “Advances in Metabolic Disorders,”vol. 10, A.J. Szabo, ed., Academic Press, New York (1983).
P. Cane, R. Artal, and R.N. Bergman, Putative hypothalamic glucoreceptors play no essential role in the response to moderate hypoglycemia, Diabetes 35:268 (1986).
P. Cane, C.K. Haun, J. Evered, J.H. Youn, and R.N. Bergman, Response to deep hypoglycemia does not involve glucoreceptors in carotid perfused tissue, Am. J. Physiol. 255:E680 (1988).
R.S. Reneman, D. Wellens, A.H.M. Jageneau, and L. Stynen, Vertebral and carotid blood distribution in the brain of the dog and the cat, Cardiovasc. Res. 8:65 (1974).
D.L.F. Wellens, J.M.R. Lucien, R.J.J. Wouters, P.B. DeReese, and R.S. Reneman, The cerebral blood distribution in dogs and cats. An anatomical and functional study, Brain Res. 86:42 (1975).
R.J. DiRocco and H.J. Grill, The forebrain is not essential for sympathoadrenal hyperglycemic response to glucoprivation, Science 204:1112 (1979).
R.C. Ritter, P.G. Slusser, and S. Stone, Glucoreceptors controlling feeding and blood glucose: Location in the hindbrain, Science 213:451 (1979).
D.W. Biggers, S.R. Myers, D. Neal, R. Stinson, N.B. Cooper, J.B. Jaspan, P.E. Williams, A.D. Cherrington, and R.T. Frizzell, Role of brain in counterregula-tion of insulin-induced hypoglycemia in dogs, Diabetes 38:7 (1989).
M. Russek, Participation of hepatic glucoreceptors in the control of intake of food, Nature 197:79 (1963).
A. Niijima, Afferent impulse discharges from glucoreceptors in the liver of the guinea pig, Ann. New York Acad. Sci. 157:690 (1969).
A. Niijima, Glucose-sensitive afferent nerve fibers in the liver and their role in food intake and blood glucose regulation, J.Autonom. Nerv. Svst. 9:207 (1983).
N.Y. Shimizu, Y. Oomura, D. Novin, C.V. Grijalva, and P.H. Cooper, Functional correlation between lateral hypothalamic glucose-sensitive neurons and hepatic portal glucose-sensitive units in rats, Brain Res. 265:49 (1983).
M. Schmitt, Influences of hepatic portal receptors on hypothalamic feeding and satiety centers, Am. J. Phvsiol. 225:1089 (1973).
A. Niijima and N. Mei, Glucose sensors in viscera and control of blood glucose level, NIPS 2:164 (1987).
E.M. Stricker, N. Rowland, C.F. Sailer, and M.I. Friedman, Homeostasis during hypoglycemia: Central control of adrenal secretion and peripheral control of feeding, Science 196:79 (1977).
C. M. Donovan, J.B. Halter, and R.N. Bergman, Importance of hepatic glucoreceptors in the sympathoadrenal response to hypoglycemia, Diabetes (In Press).
J.E. Gerich and P.J. Campell, Overview of counterregulation and its abnormalities in diabetes mellitus, Diabetes Metab. Rev. 4:93 (1988).
P.E. Cryer and J.E. Gerich, Relevance of glucose counterregulatory systems to patients with diabetes: Critical roles of glucagon and epinephrine, Diabetes Care 6:95 (1983).
S.A. Amiel, W.V. Tamborlane, L.Sacca, and R.S. Sherwin, Hypoglycemia and glucose counterregulation in normal and insulin-dependent diabetic subjects, Diabetes Metab. Rev. 4:71 (1988).
E.M. Stricker and M.J. McCann, Visceral factors in the control of food intake, Brain Res. Bull. 14:687 (1985).
J. Palmer, D. Henry, J. Benson, D. Johnson, and J. Ensinck, Glucagon response to hypoglycemia in sympathectomized man, J. Clin. Invest. 57:522 (1976).
J. Palmer, P. Werner, P. Hollander, and J. Ensinck, Evaluation of the control of glucagon secretion by the parasympathetic nervous system in man, Metabolism28:549 (1979).
R.J.M. Corrall and B.M. Frier, Acute hypoglycemia in man: central control of the pancreatic islet cell function, Metabolism 30:160 (1981).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Donovan, C.M., Cane, P., Bergman, R.N. (1991). Search for the Hypoglycemia Receptor Using the Local Irrigation Approach. In: Vranic, M., Efendic, S., Hollenberg, C.H. (eds) Fuel Homeostasis and the Nervous System. Advances in Experimental Medicine and Biology, vol 291. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5931-9_14
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5931-9_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5933-3
Online ISBN: 978-1-4684-5931-9
eBook Packages: Springer Book Archive