Research Article

Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes

Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, United States
Program in Neuroscience, Harvard Medical School, United States
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, United Kingdom
Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Denmark
Metabolic Research Unit, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden
Alberta Diabetes Institute, Li Ka Shing Centre for Health Research Innovation, Canada
Department of Clinical Biochemistry, John Radcliffe, Oxford NHS Trust, United Kingdom
Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, United Kingdom
Center for Clinical Metabolic Research, Gentofte Hospital, Denmark
Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
Department of Computer Science, University of Oxford, United Kingdom

Nov 17, 2021

https://doi.org/10.7554/eLife.72919

Open access
Copyright information

Peer review process
Decision letter
Author response

Peer review process

This article was accepted for publication as part of eLife's original publishing model.

History

Version of Record published December 8, 2021
Accepted Manuscript published November 17, 2021
Accepted November 16, 2021
Received August 9, 2021
Preprint posted July 9, 2021

Go to the preprint

Decision letter

Weiping Han

Reviewing Editor; Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore
Lu Chen

Senior Editor; Stanford University, United States

Our editorial process produces two outputs: (i) public reviews designed to be posted alongside the preprint for the benefit of readers; (ii) feedback on the manuscript for the authors, including requests for revisions, shown below. We also include an acceptance summary that explains what the editors found interesting or important about the work.

Decision letter after peer review:

Thank you for submitting your article "Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes" for consideration by eLife. Your article has been reviewed by 2 peer reviewers, and the evaluation has been overseen by a Reviewing Editor and Lu Chen as the Senior Editor. The reviewers have opted to remain anonymous.

The reviewers have discussed their reviews with one another, and the Reviewing Editor has drafted this to help you prepare a revised submission.

Essential revisions:

The comments of both reviewers can be addressed via revisions/additions to the text and figures without new experiments.

Reviewer #1 (Recommendations for the authors):

https://doi.org/10.7554/eLife.72919.sa1

Author response

In this manuscript, Angela Kim et al., use a combination of in vitro and in vivo studies to determine how glucose-control of central AVP release controls pancreatic α-cell calcium influx and glucagon secretion to modulate blood glucose homeostasis. The manuscript clearly shows that activation of AVP release from magnocellular AVP neurons stimulates pancreatic islet glucagon secretion. Furthermore, the manuscript finds AVP (measured by circulating Copeptin) is elevated in plasma following insulin induced hypoglycemia, which also activates AVP neuron electrical excitability and calcium entry. To confirm that AVP release stimulates glucagon secretion via islet α-cell Avpr1b activation, both Avpr1b antagonists and an Avpr1b-/- mouse model were utilized. Finally, the manuscript looks at plasma AVP in humans undergoing a hypoglycemic clamp; while this results in AVP release in non-diabetic controls, AVP release is blunted following hypoglycemia in type-1 diabetic patients. Based on an extensive amount of high-quality data, the authors conclude that AVP release from magnocellular AVP neurons is involved in regulating glucagon secretion in response to hypoglycemia. The manuscript is well written and easy to follow. As the exact mechanism that controls glucagon secretion is still unknown, this manuscript adds important information for the diabetes research community detailing the importance of CNS control of islet glucagon secretion through glucose regulated AVP release. Overall, this is an excellent manuscript that will be very useful to the diabetes research community.

https://doi.org/10.7554/eLife.72919.sa2