Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McCrimmon, R. J.
Right arrow Articles by Sherwin, R. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCrimmon, R. J.
Right arrow Articles by Sherwin, R. S.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:1953-1958, 2004
© 2004 by the American Diabetes Association, Inc.

Potential Role for AMP-Activated Protein Kinase in Hypoglycemia Sensing in the Ventromedial Hypothalamus

Rory J. McCrimmon, Xiaoning Fan, Yuyan Ding, Wanling Zhu, Ralph J. Jacob, and Robert S. Sherwin

From the Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, Connecticut

The mechanisms by which specialized glucose-sensing neurons within the hypothalamus are able to detect a falling blood glucose remain largely unknown but may be linked to some gauge of neuronal energy status. We sought to test the hypothesis that AMP-activated protein kinase (AMPK), an intracellular kinase purported to act as a fuel sensor, plays a role in hypoglycemia sensing in the ventromedial hypothalamus (VMH) of the Sprague-Dawley rat by chemically activating AMPK in vivo through bilateral microinjection, before performing hyperinsulinemic-hypoglycemic or hyperinsulinemic-euglycemic clamp studies. In a subgroup of rats, H3-glucose was infused to determine glucose kinetics. The additional chemical activation by AICAR of AMPK in the VMH during hypoglycemia markedly reduced the amount of exogenous glucose required to maintain plasma glucose during hypoglycemia, an effect that was almost completely accounted for by a three- to fourfold increase in hepatic glucose production in comparison to controls. In contrast, no differences were seen between groups in hypoglycemia-induced rises in the principal counterregulatory hormones. In conclusion, activation of AMPK within the VMH may play an important role in hypoglycemia sensing. The combination of hypoglycemia- and AICAR-induced AMPK activity appears to result in a marked stimulus to hepatic glucose counterregulation.

Address correspondence and reprint requests to Robert S. Sherwin, MD, Yale University School of Medicine, Section of Endocrinology, 300 Cedar St., PO Box 208020, New Haven, CT 06520-8020. E-mail: robert.sherwin{at}yale.edu


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
B. E. Levin, T. C. Becker, J.-i. Eiki, B. B. Zhang, and A. A. Dunn-Meynell
Ventromedial Hypothalamic Glucokinase Is an Important Mediator of the Counterregulatory Response to Insulin-Induced Hypoglycemia
Diabetes, May 1, 2008; 57(5): 1371 - 1379.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. J. McCrimmon, M. Shaw, X. Fan, H. Cheng, Y. Ding, M. C. Vella, L. Zhou, E. C. McNay, and R. S. Sherwin
Key Role for AMP-Activated Protein Kinase in the Ventromedial Hypothalamus in Regulating Counterregulatory Hormone Responses to Acute Hypoglycemia
Diabetes, February 1, 2008; 57(2): 444 - 450.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Garcia-Fernandez, P. Ortega-Saenz, A. Castellano, and J. Lopez-Barneo
Mechanisms of Low-Glucose Sensitivity in Carotid Body Glomus Cells
Diabetes, December 1, 2007; 56(12): 2893 - 2900.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
H. Cheng, L. Zhou, W. Zhu, A. Wang, C. Tang, O. Chan, R. S. Sherwin, and R. J. McCrimmon
Type 1 corticotropin-releasing factor receptors in the ventromedial hypothalamus promote hypoglycemia-induced hormonal counterregulation
Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E705 - E712.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
N. Marty, M. Dallaporta, and B. Thorens
Brain Glucose Sensing, Counterregulation, and Energy Homeostasis
Physiology, August 1, 2007; 22(4): 241 - 251.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
O. Chan, M. Lawson, W. Zhu, J. L. Beverly, and R. S. Sherwin
ATP-Sensitive K+ Channels Regulate the Release of GABA in the Ventromedial Hypothalamus During Hypoglycemia
Diabetes, April 1, 2007; 56(4): 1120 - 1126.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
P. D. Mountjoy and G. A. Rutter
Glucose sensing by hypothalamic neurones and pancreatic islet cells: AMPle evidence for common mechanisms?
Exp Physiol, March 1, 2007; 92(2): 311 - 319.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Gromada, I. Franklin, and C. B. Wollheim
{alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Endocr. Rev., February 1, 2007; 28(1): 84 - 116.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. K. Dash, S. A. Orsi, and A. N. Moore
Spatial Memory Formation and Memory-Enhancing Effect of Glucose Involves Activation of the Tuberous Sclerosis Complex-Mammalian Target of Rapamycin Pathway
J. Neurosci., August 2, 2006; 26(31): 8048 - 8056.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. Ramamurthy and G. V. Ronnett
Developing a head for energy sensing: AMP-activated protein kinase as a multifunctional metabolic sensor in the brain
J. Physiol., July 1, 2006; 574(1): 85 - 93.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
B. Xue and B. B. Kahn
AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues
J. Physiol., July 1, 2006; 574(1): 73 - 83.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. J. McCrimmon, X. Fan, H. Cheng, E. McNay, O. Chan, M. Shaw, Y. Ding, W. Zhu, and R. S. Sherwin
Activation of AMP-Activated Protein Kinase Within the Ventromedial Hypothalamus Amplifies Counterregulatory Hormone Responses in Rats With Defective Counterregulation
Diabetes, June 1, 2006; 55(6): 1755 - 1760.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
O. Chan, W. Zhu, Y. Ding, R. J. McCrimmon, and R. S. Sherwin
Blockade of GABAA Receptors in the Ventromedial Hypothalamus Further Stimulates Glucagon and Sympathoadrenal but Not the Hypothalamo-Pituitary-Adrenal Response to Hypoglycemia.
Diabetes, April 1, 2006; 55(4): 1080 - 1087.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
P. E. Cryer
Mechanisms of Hypoglycemia-Associated Autonomic Failure and Its Component Syndromes in Diabetes
Diabetes, December 1, 2005; 54(12): 3592 - 3601.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. C. Camacho, D. B. Lacy, F. D. James, E. P. Donahue, and D. H. Wasserman
5-Aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside renders glucose output by the liver of the dog insensitive to a pharmacological increment in insulin
Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1039 - E1043.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. J. McCrimmon, M. L. Evans, X. Fan, E. C. McNay, O. Chan, Y. Ding, W. Zhu, D. X. Gram, and R. S. Sherwin
Activation of ATP-Sensitive K+ Channels in the Ventromedial Hypothalamus Amplifies Counterregulatory Hormone Responses to Hypoglycemia in Normal and Recurrently Hypoglycemic Rats
Diabetes, November 1, 2005; 54(11): 3169 - 3174.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. C. Camacho, R. R. Pencek, D. B. Lacy, F. D. James, E. P. Donahue, and D. H. Wasserman
Portal Venous 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside Infusion Overcomes Hyperinsulinemic Suppression of Endogenous Glucose Output
Diabetes, February 1, 2005; 54(2): 373 - 382.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
V. Locatelli and A. Torsello
Pyruvate and Satiety: Can We Fool the Brain?
Endocrinology, January 1, 2005; 146(1): 1 - 2.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.