Deciphering the hypoglycemic glucagon response: development of a graded hyperinsulinemic hypoglycemic clamp technique in female mice.
(2015) In Endocrinology 156(10). p.3866-3871- Abstract
- Glucose lowering therapy in type 1 and type 2 diabetes is often associated with hypoglycemic events. To avoid this, glucose lowering therapies need to be developed that support the hypoglycemic defense mechanisms. Such development needs a tool for evaluating counterregulatory mechanisms in vivo. A sustained glucagon release during hypoglycemia is of most importance to hypoglycemic defense mechanisms. We have therefore developed a graded hyperinsulinemic hypoglycemic clamp in mice and used it to evaluate counterregulatory glucagon dynamics. Glucose was clamped at narrow intervals aiming at 2.5, 3.5, 4.5 and 6.0 mmol/L. Glucagon levels were increased during hypoglycemia in a glucose-dependent way with a glucagon counterregulatory threshold... (More)
- Glucose lowering therapy in type 1 and type 2 diabetes is often associated with hypoglycemic events. To avoid this, glucose lowering therapies need to be developed that support the hypoglycemic defense mechanisms. Such development needs a tool for evaluating counterregulatory mechanisms in vivo. A sustained glucagon release during hypoglycemia is of most importance to hypoglycemic defense mechanisms. We have therefore developed a graded hyperinsulinemic hypoglycemic clamp in mice and used it to evaluate counterregulatory glucagon dynamics. Glucose was clamped at narrow intervals aiming at 2.5, 3.5, 4.5 and 6.0 mmol/L. Glucagon levels were increased during hypoglycemia in a glucose-dependent way with a glucagon counterregulatory threshold between 3.5 and 4.0 mmol/L. Modelling the glucose - glucagon relationship using a hyperbolic curve with the equation: Plasma glucagon=-4.20+90.79/blood glucose showed high correlation. When comparing this method to the insulin tolerance test (ITT) as an approach to study glucagon dynamics in vivo we found that the graded clamp more efficiently evoked a robust, predictable, glucagon response with considerably less variation in blood glucose. In conclusion, we have developed a tool for the study of in vivo glucagon dynamics during hypoglycemia in mice and demonstrated a hyperbolic glucose-counterregulatory glucagon relationship. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7751142
- author
- Malmgren, Siri LU and Ahrén, Bo LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Endocrinology
- volume
- 156
- issue
- 10
- pages
- 3866 - 3871
- publisher
- Oxford University Press
- external identifiers
-
- pmid:26132921
- wos:000362235300049
- scopus:84943645698
- pmid:26132921
- ISSN
- 0013-7227
- DOI
- 10.1210/EN.2015-1314
- language
- English
- LU publication?
- yes
- id
- 9a0bd99e-cc8b-4541-ab8c-3f7dda18c996 (old id 7751142)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26132921?dopt=Abstract
- date added to LUP
- 2016-04-01 11:13:39
- date last changed
- 2024-10-08 00:04:16
@article{9a0bd99e-cc8b-4541-ab8c-3f7dda18c996, abstract = {{Glucose lowering therapy in type 1 and type 2 diabetes is often associated with hypoglycemic events. To avoid this, glucose lowering therapies need to be developed that support the hypoglycemic defense mechanisms. Such development needs a tool for evaluating counterregulatory mechanisms in vivo. A sustained glucagon release during hypoglycemia is of most importance to hypoglycemic defense mechanisms. We have therefore developed a graded hyperinsulinemic hypoglycemic clamp in mice and used it to evaluate counterregulatory glucagon dynamics. Glucose was clamped at narrow intervals aiming at 2.5, 3.5, 4.5 and 6.0 mmol/L. Glucagon levels were increased during hypoglycemia in a glucose-dependent way with a glucagon counterregulatory threshold between 3.5 and 4.0 mmol/L. Modelling the glucose - glucagon relationship using a hyperbolic curve with the equation: Plasma glucagon=-4.20+90.79/blood glucose showed high correlation. When comparing this method to the insulin tolerance test (ITT) as an approach to study glucagon dynamics in vivo we found that the graded clamp more efficiently evoked a robust, predictable, glucagon response with considerably less variation in blood glucose. In conclusion, we have developed a tool for the study of in vivo glucagon dynamics during hypoglycemia in mice and demonstrated a hyperbolic glucose-counterregulatory glucagon relationship.}}, author = {{Malmgren, Siri and Ahrén, Bo}}, issn = {{0013-7227}}, language = {{eng}}, number = {{10}}, pages = {{3866--3871}}, publisher = {{Oxford University Press}}, series = {{Endocrinology}}, title = {{Deciphering the hypoglycemic glucagon response: development of a graded hyperinsulinemic hypoglycemic clamp technique in female mice.}}, url = {{http://dx.doi.org/10.1210/EN.2015-1314}}, doi = {{10.1210/EN.2015-1314}}, volume = {{156}}, year = {{2015}}, }