HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/R1283    most recent 00148.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Song, Z. Articles by Routh, V. H. Search for Related Content PubMed PubMed Citation Articles by Song, Z. Articles by Routh, V. H.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

Recurrent hypoglycemia reduces the glucose sensitivity of glucose-inhibited neurons in the ventromedial hypothalamus nucleus

Department of Pharmacology and Physiology, New Jersey Medical School, Newark, New Jersey

Submitted 2 March 2006 ; accepted in final form 19 June 2006

Recurrent hypoglycemia blunts the brain's ability to sense and respond to subsequent hypoglycemic episodes. Glucose-sensing neurons in the ventromedial hypothalamus nucleus (VMN) are well situated to play a role in hypoglycemia detection. VMN glucose-inhibited (GI) neurons, which decrease their firing rate as extracellular glucose increases, are extremely sensitive to decreased extracellular glucose. We hypothesize that recurrent hypoglycemia decreases the glucose sensitivity of VMN GI neurons. To test our hypothesis, 14- to 21-day-old Sprague-Dawley rats were subcutaneously injected with regular human insulin (4 U/kg) or saline (control) for three consecutive days. Blood glucose levels 1 h after insulin injection on day 3 were significantly lower than on day 1, reflecting an impaired ability to counteract hypoglycemia. On day 4, the glucose sensitivity of VMN GI neurons was measured using conventional whole cell current-clamp recording. After recurrent insulin-induced hypoglycemia, VMN GI neurons only responded to a glucose decrease from 2.5 to 0.1, but not 0.5, mM. Additionally, lactate supplementation also decreased glucose sensitivity of VMN GI neurons. Thus our findings suggest that decreases in glucose sensitivity of VMN GI neurons may contribute to the impairments in central glucose-sensing mechanisms after recurrent hypoglycemia.

insulin; lactate; counterregulatory response; hypoglycemia-associated autonomic failure; whole cell current recording

This article has been cited by other articles:

				R. McCrimmon Glucose Sensing During Hypoglycemia: Lessons From the Lab Diabetes Care, August 1, 2009; 32(8): 1357 - 1363. [Full Text] [PDF]

				B. A. Murphy, X. Fioramonti, N. Jochnowitz, K. Fakira, K. Gagen, S. Contie, A. Lorsignol, L. Penicaud, W. J. Martin, and V. H. Routh Fasting enhances the response of arcuate neuropeptide Y-glucose-inhibited neurons to decreased extracellular glucose Am J Physiol Cell Physiol, April 1, 2009; 296(4): C746 - C756. [Abstract] [Full Text] [PDF]

				B. A. Murphy, K. A. Fakira, Z. Song, A. Beuve, and V. H. Routh AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucose-inhibited neurons Am J Physiol Cell Physiol, January 1, 2009; 297(3): C750 - C758. [Abstract] [Full Text] [PDF]

				S. Al-Noori, N. M. Sanders, G. J. Taborsky Jr., C. W. Wilkinson, A. Zavosh, C. West, C. M. Sanders, and D. P. Figlewicz Recurrent hypoglycemia alters hypothalamic expression of the regulatory proteins FosB and synaptophysin Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1446 - R1454. [Abstract] [Full Text] [PDF]

				L. Kang, N. M. Sanders, A. A. Dunn-Meynell, L. D. Gaspers, V. H. Routh, A. P. Thomas, and B. E. Levin Prior hypoglycemia enhances glucose responsiveness in some ventromedial hypothalamic glucosensing neurons Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R784 - R792. [Abstract] [Full Text] [PDF]

				A. V. Matveyenko, M. Bohland, M. Saberi, and C. M. Donovan Portal vein hypoglycemia is essential for full induction of hypoglycemia-associated autonomic failure with slow-onset hypoglycemia Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E857 - E864. [Abstract] [Full Text] [PDF]

				S. Polakof, J. M. Miguez, and J. L. Soengas In vitro evidences for glucosensing capacity and mechanisms in hypothalamus, hindbrain, and Brockmann bodies of rainbow trout Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1410 - R1420. [Abstract] [Full Text] [PDF]

				D. D. Canabal, J. G. Potian, R. G. Duran, J. J. McArdle, and V. H. Routh Hyperglycemia impairs glucose and insulin regulation of nitric oxide production in glucose-inhibited neurons in the ventromedial hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R592 - R600. [Abstract] [Full Text] [PDF]

				M. B. Barnes and J. L. Beverly Nitric oxide's role in glucose homeostasis Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R590 - R591. [Full Text] [PDF]

				D. D. Canabal, Z. Song, J. G. Potian, A. Beuve, J. J. McArdle, and V. H. Routh Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1418 - R1428. [Abstract] [Full Text] [PDF]

				N. M. Sanders, G. J. Taborsky Jr., C. W. Wilkinson, W. Daumen, and D. P. Figlewicz Antecedent Hindbrain Glucoprivation Does Not Impair the Counterregulatory Response to Hypoglycemia Diabetes, January 1, 2007; 56(1): 217 - 223. [Abstract] [Full Text] [PDF]