2.50
Hdl Handle:
http://hdl.handle.net/10755/163480
Category:
Abstract
Type:
Presentation
Title:
Characterizing brain responses in a rodent model of hypoglycemia unawareness
Author(s):
Tkacs, Nancy
Author Details:
Nancy Tkacs, University of Pennsylvania, School of Nursing, Philadelphia, Pennsylvania, USA, email: tkacs@nursing.upenn.edu
Abstract:
Purpose: To elucidate brain mechanisms underlying hypoglycemia unawareness and hypoglycemia-associated autonomic failure (HAAF) by using a rodent model. Research question: Intensive management of type 1 diabetes mellitus is associated with increased incidence of hypoglycemia. Recurrent hypoglycemia leads to reduced conscious perception of hypoglycemia (hypoglycemia unawareness) and to reduced autonomic and hormone responses to hypoglycemia (HAAF). The specific aim of this study was to map brain regions activated by hypoglycemia in rats, to identify candidate brain regions subject to hypoglycemia-induced alterations. Rationale: Mechanistic studies of hypoglycemia unawareness can be used to develop targeted strategies for managing this complication of insulin-treated diabetes mellitus. A rodent model can provide basic information on the vulnerability of the brain to the state of hypoglycemia. Methods: Rats were surgically prepared with indwelling catheters for blood sampling. After recovery, rats were fasted overnight for testing in the morning. Three treatment groups were compared: 1. Overnight fast followed by intravenous saline injection (saline controls). 2. Overnight fast followed by insulin-induced hypoglycemia, terminated with a bolus injection of 50% dextrose (hypo - D50 group). 3. Overnight fast followed by insulin-induced hypoglycemia terminated with 50% dextrose followed by food (hypo-food). One hour after terminating the hypoglycemic episode or two hours after saline injection in controls, the rats were deeply anesthetized with sodium pentobarbital and brains were collected for analysis. Results and conclusions: Hypoglycemia activated hypothalamic and brainstem regions that participate in endocrine and autonomic control. Compared with fasted controls, all hypoglycemic rats had significantly greater numbers of activated neurons in the hypothalamic arcuate nucleus, and significantly lower numbers of activated neurons in the hypothalamic ventromedial nucleus. This confirms an earlier finding from this lab implicating the arcuate nucleus of the hypothalamus in the integrated response to hypoglycemia. In addition, this result suggests that altered gene expression in the arcuate nucleus after an episode of hypoglycemia may contribute to prolonged down-regulation of responses to hypoglycemia. Implications: Evaluation of arcuate nucleus integrity may be one way to assess interventions designed to reduce the incidence of hypoglycemia unawareness and HAAF. Greater understanding of the neurophysiological basis of hypoglycemia unawareness and HAAF will ultimately contribute to development of interventions to reduce these dangerous sequelae of intensive diabetes management.
Repository Posting Date:
27-Oct-2011
Date of Publication:
27-Oct-2011
Conference Date:
2002
Conference Name:
14th Annual Scientific Sessions
Conference Host:
Eastern Nursing Research Society
Conference Location:
University Park, Pennsylvania, USA
Note:
This is an abstract-only submission. If the author has submitted a full-text item based on this abstract, you may find it by browsing the Virginia Henderson Global Nursing e-Repository by author. If author contact information is available in this abstract, please feel free to contact him or her with your queries regarding this submission. Alternatively, please contact the conference host, journal, or publisher (according to the circumstance) for further details regarding this item. If a citation is listed in this record, the item has been published and is available via open-access avenues or a journal/database subscription. Contact your library for assistance in obtaining the as-published article.

Full metadata record

DC FieldValue Language
dc.type.categoryAbstracten_US
dc.typePresentationen_GB
dc.titleCharacterizing brain responses in a rodent model of hypoglycemia unawarenessen_GB
dc.contributor.authorTkacs, Nancyen_US
dc.author.detailsNancy Tkacs, University of Pennsylvania, School of Nursing, Philadelphia, Pennsylvania, USA, email: tkacs@nursing.upenn.eduen_US
dc.identifier.urihttp://hdl.handle.net/10755/163480-
dc.description.abstractPurpose: To elucidate brain mechanisms underlying hypoglycemia unawareness and hypoglycemia-associated autonomic failure (HAAF) by using a rodent model. Research question: Intensive management of type 1 diabetes mellitus is associated with increased incidence of hypoglycemia. Recurrent hypoglycemia leads to reduced conscious perception of hypoglycemia (hypoglycemia unawareness) and to reduced autonomic and hormone responses to hypoglycemia (HAAF). The specific aim of this study was to map brain regions activated by hypoglycemia in rats, to identify candidate brain regions subject to hypoglycemia-induced alterations. Rationale: Mechanistic studies of hypoglycemia unawareness can be used to develop targeted strategies for managing this complication of insulin-treated diabetes mellitus. A rodent model can provide basic information on the vulnerability of the brain to the state of hypoglycemia. Methods: Rats were surgically prepared with indwelling catheters for blood sampling. After recovery, rats were fasted overnight for testing in the morning. Three treatment groups were compared: 1. Overnight fast followed by intravenous saline injection (saline controls). 2. Overnight fast followed by insulin-induced hypoglycemia, terminated with a bolus injection of 50% dextrose (hypo - D50 group). 3. Overnight fast followed by insulin-induced hypoglycemia terminated with 50% dextrose followed by food (hypo-food). One hour after terminating the hypoglycemic episode or two hours after saline injection in controls, the rats were deeply anesthetized with sodium pentobarbital and brains were collected for analysis. Results and conclusions: Hypoglycemia activated hypothalamic and brainstem regions that participate in endocrine and autonomic control. Compared with fasted controls, all hypoglycemic rats had significantly greater numbers of activated neurons in the hypothalamic arcuate nucleus, and significantly lower numbers of activated neurons in the hypothalamic ventromedial nucleus. This confirms an earlier finding from this lab implicating the arcuate nucleus of the hypothalamus in the integrated response to hypoglycemia. In addition, this result suggests that altered gene expression in the arcuate nucleus after an episode of hypoglycemia may contribute to prolonged down-regulation of responses to hypoglycemia. Implications: Evaluation of arcuate nucleus integrity may be one way to assess interventions designed to reduce the incidence of hypoglycemia unawareness and HAAF. Greater understanding of the neurophysiological basis of hypoglycemia unawareness and HAAF will ultimately contribute to development of interventions to reduce these dangerous sequelae of intensive diabetes management.en_GB
dc.date.available2011-10-27T11:08:18Z-
dc.date.issued2011-10-27en_GB
dc.date.accessioned2011-10-27T11:08:18Z-
dc.conference.date2002en_US
dc.conference.name14th Annual Scientific Sessionsen_US
dc.conference.hostEastern Nursing Research Societyen_US
dc.conference.locationUniversity Park, Pennsylvania, USAen_US
dc.description.noteThis is an abstract-only submission. If the author has submitted a full-text item based on this abstract, you may find it by browsing the Virginia Henderson Global Nursing e-Repository by author. If author contact information is available in this abstract, please feel free to contact him or her with your queries regarding this submission. Alternatively, please contact the conference host, journal, or publisher (according to the circumstance) for further details regarding this item. If a citation is listed in this record, the item has been published and is available via open-access avenues or a journal/database subscription. Contact your library for assistance in obtaining the as-published article.-
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