Evidence mapPaperPMID 41206007Full record

ArticleThe Journal of clinical endocrinology and metabolism2026

HMGCR and Rosuvastatin Regulates GLP-1 Secretion and Expression-A Translational Study.

Michael G Miskelly, Andreas Lindqvist, Amra Jujić, Alexander Hamilton, Elaine Cowan, Sweta Raikundalia, Anna-Maria Dutius Andersson, Bent J Nergård, Rita Del Giudice, Dmytro Kryvokhyzha and 10 more

Abstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Michael G MiskellyNeuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö 21428, Sweden.ORCID 0000-0002-4688-5719
Andreas LindqvistNeuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö 21428, Sweden.ORCID 0009-0000-8287-5609
Amra JujićDepartment of Clinical Sciences, Lund University, Malmö 21428, Sweden.ORCID 0000-0002-9506-0158
Alexander HamiltonUnit of Molecular Metabolism, Lund University Diabetes Centre, Malmö 21428, Sweden.ORCID 0000-0001-5203-9220
Elaine CowanIslet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö 21428, Sweden.ORCID 0000-0003-3939-8864
Sweta RaikundaliaNeuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö 21428, Sweden.ORCID 0000-0003-4604-153X
Anna-Maria Dutius AnderssonDiabetic Complications Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Malmö 21428, Sweden.
Bent J NergårdAleris Obesitas, Lund 22270, Sweden.
Rita Del GiudiceDepartment of Experimental Medical Science, Lund University, Lund 22100, Sweden.ORCID 0000-0002-9927-9413
Dmytro KryvokhyzhaDepartment of Clinical Sciences, Lund University, Malmö 21428, Sweden.ORCID 0000-0001-6498-1977
Peter M NilssonDepartment of Clinical Sciences, Lund University, Malmö 21428, Sweden.ORCID 0000-0002-5652-8459
Jens Juul HolstDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen 2200, Denmark.ORCID 0000-0001-6853-3805
Signe Sørensen TorekovDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen 2200, Denmark.ORCID 0000-0001-6779-0252
Jens O LagerstedtIslet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö 21428, Sweden.ORCID 0000-0002-4313-2666
Maria F GomezDiabetic Complications Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Malmö 21428, Sweden.ORCID 0000-0001-6210-3142
Lena EliassonIslet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö 21428, Sweden.ORCID 0000-0002-6467-5029
Hindrik MulderUnit of Molecular Metabolism, Lund University Diabetes Centre, Malmö 21428, Sweden.ORCID 0000-0002-6593-8417
Jan HedenbroNeuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö 21428, Sweden.ORCID 0000-0001-7479-9087
Martin MagnussonDepartment of Clinical Sciences, Lund University, Malmö 21428, Sweden.ORCID 0000-0003-1710-5936
Nils WierupNeuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University, Malmö 21428, Sweden.ORCID 0000-0001-6824-4093

Funding

Albert Påhlsson FoundationDiabetes Wellness Research Foundation SwedenErnhold Lundstrom FoundationEuropean Union's Researchgrants from the Medical Faculty of Lund University Skane University HospitalHorizon 2020JDRFLund University Diabetes CentreMedical Research Council of Sweden K2011-65X-20752-04-6Region SkåneRegion Skåne and the Swedish Heart and Lung foundation 2019-0470Region Skåne and the Swedish Heart and Lung foundation 2021-0354Region Skåne County CouncilRoyal Physiographic Society in LundSwedish Diabetes Foundation DIA2022-723Swedish Foundation for Strategic Research IRC15-0067Swedish Research Council 2017-00862Swedish Research Council 2018-02837Swedish Research Council 2019-01406Swedish Research Council 2020-01017Swedish Research Council 2020-02179Swedish Research Council 2022-00973Swedish Research Council 2024-03413Swedish Research Council 349-2006-237the Innovative Medicines Initiative 115974Wallenberg Center for Molecular Medicine
6 · The paper itself

Abstract

contextStatin use is associated with increased risk of type 2 diabetes (T2D) and mild hyperglycemia. The underlying mechanisms are not well studied, and the effect of statin treatment on glucagon-like peptide 1 (GLP-1) secretion or production is unknown.

objectiveThis work aimed to assess the effects of rosuvastatin on GLP-1 secretion and production.

methodsWe performed association studies in the Malmö Diet and Cancer study cardiovascular cohort (MDCS-CC) reexamination cohort, in vitro investigations using GLUTag cells and acute and chronic studies in female, normoglycemic C57Bl/6j mice.

resultsStudies in the MDCS-CC reexamination cohort (n = 3734) revealed that in individuals without T2D, statin usage was associated with higher fasting glucose-dependent insulinotropic peptide (GIP), insulin, glucose, glucagon, and homeostatic model assessment of insulin resistance, but not GLP-1. However, in patients with T2D, statin usage was associated with higher fasting GLP-1 levels. Rosuvastatin treatment or 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr) knockdown (KD) reduced GLP-1 secretion and increased Gcg messenger RNA in GLUTag cells. Rosuvastatin acutely reduced postprandial GLP-1 secretion, whereas chronic rosuvastatin treatment in mice caused hyperglycemia and increased postprandial GLP-1 levels. The acute effect of Hmgcr KD on GLP-1 secretion could be mimicked by targeting intracellular cholesterol using a PCSK9 inhibitor. Finally, transcriptomic alterations induced by rosuvastatin were limited to genes involved in cholesterol biosynthesis.

conclusionWe have established HMGCR as a regulator of GLP-1 secretion and provide a plausible explanation for the clinically observed mild hyperglycemia associated with statin use. Given the negative acute effect on GLP-1 secretion, monitoring of blood glucose levels is recommended after prescribing rosuvastatin.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide 1Hydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesRosuvastatin CalciumAgedAnimalsBlood GlucoseCohort StudiesFemaleHumansHyperglycemiaMaleMiceMice, Inbred C57BLMiddle AgedBlood GlucoseGlucagon-Like Peptide 1HMGCR protein, humanHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl CoA ReductasesRosuvastatin CalciumGLP-1glucose homeostasisHMGCRincretinsrosuvastatintype 2 diabetes

Identifiers

PMID41206007
PMCPMC13099218

What Socratic holds

Texttitle and abstract
LicenceCC BY
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Registered trials

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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 Socratic graph.