AJP - Endo Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 295: E575-E585, 2008. First published June 24, 2008; doi:10.1152/ajpendo.90372.2008
0193-1849/08 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
295/3/E575    most recent
90372.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Farhy, L. S.
Right arrow Articles by McCall, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farhy, L. S.
Right arrow Articles by McCall, A. L.

Amplification of pulsatile glucagon counterregulation by switch-off of {alpha}-cell-suppressing signals in streptozotocin-treated rats

Leon S. Farhy,1,4 Zhongmin Du,1 Qiang Zeng,3 Paula P. Veldhuis,4 Michael L. Johnson,1,2,4 Kenneth L. Brayman,3 and Anthony L. McCall1

Departments of 1Medicine, 2Pharmacology, and 3Surgery and 4Center for Biomathematical Technology, University of Virginia, Charlottesville, Virginia

Submitted 16 April 2008 ; accepted in final form 23 June 2008

Glucagon counterregulation (GCR) is a key protection against hypoglycemia that is compromised in diabetes via an unknown mechanism. To test the hypothesis that {alpha}-cell-inhibiting signals that are switched off during hypoglycemia amplify GCR, we studied streptozotocin (STZ)-treated male Wistar rats and estimated the effect on GCR of intrapancreatic infusion and termination during hypoglycemia of saline, insulin, and somatostatin. Times 10 min before and 45 min after the switch-off were analyzed. Insulin and somatostatin, but not saline, switch-off significantly increased the glucagon levels (P = 0.03), and the fold increases relative to baseline were significantly higher (P < 0.05) in the insulin and somatostatin groups vs. the saline group. The peak concentrations were also higher in the insulin (368 pg/ml) and somatostatin (228 pg/ml) groups vs. the saline (114 pg/ml) group (P < 0.05). GCR was pulsatile in most animals, indicating a feedback regulation. After the switch-off, the number of secretory events and the total pulsatile production were lower in the saline group vs. the insulin and somatostatin groups (P < 0.05), indicating enhancement of glucagon pulsatile activity by insulin and somatostatin compared with saline. Network modeling analysis demonstrates that reciprocal interactions between {alpha}- and {delta}-cells can explain the amplification by interpreting the GCR as a rebound response to the switch-off. The model justifies experimental designs to further study the intrapancreatic network in relation to the switch-off phenomenon. The results of this proof-of-concept interdisciplinary study support the hypothesis that GCR develops as a rebound pulsatile response of the intrapancreatic endocrine feedback network to switch-off of {alpha}-cell-inhibiting islet signals.

pancreatic endocrine network; feedback control; insulin; somatostatin


Address for reprint requests and other correspondence: L. S. Farhy, Box 800735, Univ. of Virginia Health System, Charlottesville, VA 22908 (e-mail: leon{at}virginia.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.