University of California Davis
University of Cincinnati Medical Center
University of Massachusetts Medical School
University of Michigan Medical School
Vanderbilt University School of Medicine
Protocols & Methods
Reagents & Resources
Tissues & Samples
Conditions of Use
Data Usage Policy
Energy Expenditure Analysis
CalR: Indirect Calorimetry Analysis
Guidelines & Policies
Hypothalamic POMC or MC4R deficiency impairs counterregulatory responses to
hypoglycemia in mice.
Tooke BP, Yu H, Adams JM, Jones GL, Sutton-Kennedy T, Mundada L, Qi NR, Low MJ,
Submitted Externally on 4/15/2019
Volume : Pages
20 : 194 - 204
Life-threatening hypoglycemia is a major limiting factor in the management of
diabetes. While it is known that counterregulatory responses to hypoglycemia are
impaired in diabetes, molecular mechanisms underlying the reduced responses
remain unclear. Given the established roles of the hypothalamic
proopiomelanocortin (POMC)/melanocortin 4 receptor (MC4R) circuit in regulating
sympathetic nervous system (SNS) activity and the SNS in stimulating
counterregulatory responses to hypoglycemia, we hypothesized that hypothalamic
POMC as well as MC4R, a receptor for POMC derived melanocyte stimulating
hormones, is required for normal hypoglycemia counterregulation., To test the
hypothesis, we induced hypoglycemia or glucopenia in separate cohorts of mice
deficient in either POMC or MC4R in the arcuate nucleus (ARC) or the
paraventricular nucleus of the hypothalamus (PVH), respectively, and measured
their circulating counterregulatory hormones. In addition, we performed a
hyperinsulinemic-hypoglycemic clamp study to further validate the function of
MC4R in hypoglycemia counterregulation. We also measured Pomc and Mc4r mRNA
levels in the ARC and PVH, respectively, in the streptozotocin-induced type 1
diabetes mouse model and non-obese diabetic (NOD) mice to delineate molecular
mechanisms by which diabetes deteriorates the defense systems against
hypoglycemia. Finally, we treated diabetic mice with the MC4R agonist MTII,
administered stereotaxically into the PVH, to determine its potential for
restoring the counterregulatory response to hypoglycemia in diabetes.,
Stimulation of epinephrine and glucagon release in response to hypoglycemia or
glucopenia was diminished in both POMC- and MC4R-deficient mice, relative to
their littermate controls. Similarly, the counterregulatory response was
impaired in association with decreased hypothalamic Pomc and Mc4r expression in
the diabetic mice, a phenotype that was not reversed by insulin treatment which
normalized glycemia. In contrast, infusion of an MC4R agonist in the PVH
restored the counterregulatory response in diabetic mice., In conclusion,
hypothalamic Pomc as well as Mc4r, both of which are reduced in type 1 diabetic
mice, are required for normal counterregulatory responses to hypoglycemia.
Therefore, enhancing MC4R function may improve hypoglycemia counterregulation in
Back to Top
There was a problem with the page:
Safari Browser Detected...
We strive to make the MMPC site compatable with as many browsers as possible, but some of our third party tools don't work with the Safari browser.
In order to explore this site we highly recommend using the most recent versions of the following browsers:
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the MMPC using the following text:
Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
) under the MICROMouse Program, grants DK076169.
Citation text and image have been copied to your clipboard. You may now paste them into your document. Thank you!
Warranty disclaimer and copyright notice
THE NATIONAL MMPC MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".
The Mouse Metabolic Phenotyping Centers (MMPC) is an NIDDK funded consortium and adheres to the
NIH Data Sharing Policy
MMPC clients make their data freely available whereby MMPC users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC using the following text: 'The MMPC data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
)'. To cite specific MMPC centers, please use the appropriate RRID available from the MMPC website (
Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.
It is expected that MMPC users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC (such as summary data) and any plots, tables or screenshots depicting those data.
It is possible for invalid or incomplete results to be presented on the MMPC web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.
Data contributors and data users may not use MMPC in any unlawful manner, or in any manner that could impair MMPC services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.
The MMPC is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.
Interested in receiving MMPC News?
2017 National MMPC. All Rights Reserved.