Evidence map›Paper›PMID 30635569›Full record

ArticleNature communications2019

Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion.

Elisa Vergari, Jakob G Knudsen, Reshma Ramracheya, Albert Salehi, Quan Zhang, Julie Adam, Ingrid Wernstedt Asterholm, Anna Benrick, Linford J B Briant, Margarita V Chibalina and 10 more

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
21.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04079881 phase1 / phase2terminatednot on this mapstarted 2020, after this paper: background citation

Glucagon Response to Prandial Insulin Administration in Persons With Type 1 Diabetes

TypeinterventionalSponsorWashington University School of MedicineRan2020 to 2020Enrolled1ConditionsType 1 Diabetes, Hyperglycemia, PostprandialArmsInsulin
NCT05616273 completednot on this mapstarted 2023, after this paper: background citation

Stimulated Glucagon as a Biomarker of Hypoglycemic Risk in Type 1 Diabetes

TypeobservationalSponsorUniversity of ExeterRan2023 to 2025Enrolled62ConditionsType 1 Diabetes, HypoglycemiaArmsMixed Meal Tolerance Test (MMTT), Arginine Stimulation Test (AST), Home Finger Prick Sample
3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 155 citations in OpenAlex.

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  18. Dehydration-induced AVP stimulates glucagon release and ketogenesis.American journal of physiology. Endocrinology and metabolism · 2025
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 2 countries.

Elisa VergariRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Jakob G KnudsenRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Reshma RamracheyaRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Albert SalehiDepartment of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, Box 430, Göteborg, SE40530, Sweden.ORCID http://orcid.org/0000-0001-6120-3539
Quan ZhangRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.ORCID http://orcid.org/0000-0002-3626-4855
Julie AdamRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.ORCID http://orcid.org/0000-0002-7980-7151
Ingrid Wernstedt AsterholmDepartment of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, Box 430, Göteborg, SE40530, Sweden.
Anna BenrickDepartment of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, Box 430, Göteborg, SE40530, Sweden.
Linford J B BriantRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Margarita V ChibalinaRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Fiona M GribbleCambridge Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0002-4232-2898
Alexander HamiltonRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Benoit HastoyRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.ORCID http://orcid.org/0000-0003-1244-7857
Frank ReimannCambridge Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0QQ, UK.ORCID http://orcid.org/0000-0001-9399-6377
Nils J G RorsmanRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Ioannis I SpiliotisRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Andrei TarasovRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK.
Yanling WuDepartment of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, Box 430, Göteborg, SE40530, Sweden.
Frances M AshcroftDepartment of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, Box 430, Göteborg, SE40530, Sweden.
Patrik RorsmanRadcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LE, UK. patrik.rorsman@drl.ox.ac.uk.ORCID http://orcid.org/0000-0001-7578-0767
Churchill Hospital · GBUniversity of Gothenburg · SEUniversity of Cambridge · GBCentre for Human Genetics · GB

Funding

Medical Research Council G0801995Medical Research Council MC_UU_00014/3Medical Research Council MC_UU_00014/5Medical Research Council MC_UU_12012/3Medical Research Council MR/T002107/1Wellcome Trust 095531/Z/11/ZWellcome Trust 201325/Z/16/Z
6 · The paper itself

Abstract

Hypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit glucagon secretion by an indirect (paracrine) mechanism mediated by stimulation of intra-islet somatostatin release. Insulin's capacity to inhibit glucagon secretion is lost following genetic ablation of insulin receptors in the somatostatin-secreting δ-cells, when insulin-induced somatostatin secretion is suppressed by dapagliflozin (an inhibitor of sodium-glucose co-tranporter-2; SGLT2) or when the action of secreted somatostatin is prevented by somatostatin receptor (SSTR) antagonists. Administration of these compounds in vivo antagonises insulin's hypoglycaemic effect. We extend these data to isolated human islets. We propose that SSTR or SGLT2 antagonists should be considered as adjuncts to insulin in diabetes therapy.

Indexed as

AnimalsBenzhydryl CompoundsBlood GlucoseDiabetes MellitusFemaleGlucagonGlucagon-Secreting CellsGlucosidesHumansHypoglycemiaInsulinMaleMiceMice, Inbred C57BLMice, KnockoutReceptor, InsulinBenzhydryl CompoundsBlood GlucosedapagliflozinGlucagonGlucosidesInsulinReceptor, InsulinReceptors, SomatostatinSlc5a2 protein, mouseSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsSomatostatin

Identifiers

PMID30635569
PMCPMC6329806
OpenAlexW2910978360

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.