Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets.

Animals Antibodies, Monoclonal / pharmacology Blood Glucose / metabolism C-Peptide / metabolism Cell Lineage / drug effects Cell Transdifferentiation / drug effects Diabetes Mellitus, Experimental / genetics Diabetes Mellitus, Type 1 / genetics Gene Expression Glucagon / antagonists & inhibitors Glucagon-Secreting Cells / drug effects Humans Hypoglycemic Agents / pharmacology Insulin / metabolism Insulin-Secreting Cells / drug effects Islets of Langerhans / metabolism Islets of Langerhans Transplantation Mice Mice, Inbred NOD Organ Size / drug effects Receptors, Glucagon / antagonists & inhibitors Treatment Outcome
diabetes glucagon insulin islet regeneration

Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
02 03 2021
Historique:
entrez: 23 2 2021
pubmed: 24 2 2021
medline: 5 8 2021
Statut: ppublish

Résumé

We evaluated the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents. We noted durable and sustained improvements in glycemia which persist long after treatment withdrawal. Ab-4 promoted β-cell survival and enhanced the recovery of insulin

Identifiants

DOI: 10.1073/pnas.2022142118 PMID: 33619103 PMC: PMC7936318
pubmed: 33619103
pii: 2022142118
doi: 10.1073/pnas.2022142118
pmc: PMC7936318
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Blood Glucose 0
C-Peptide 0
Hypoglycemic Agents 0
Insulin 0
Receptors, Glucagon 0
Glucagon 9007-92-5

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK108833
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK104211
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK098085
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK098085
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK112232
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117147
Pays : United States
Organisme : BLRD VA
ID : I01 BX000666
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020593
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK106755
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK117969
Pays : United States

Informations de copyright

Copyright © 2021 the Author(s). Published by PNAS.

Déclaration de conflit d'intérêts

Competing interest statement: R.H.U. is a founding scientist of SynAlpha Therapeutics, LLC. K.W.S., A.M.E., and R.E.G. are employees and shareholders of Eli Lilly and Company.

Références

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Auteurs

May-Yun Wang (MY)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Medical Service, Veterans Administration North Texas Health Care System, Dallas, TX 75216.

E Danielle Dean (ED)

Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232.
ORCID: 0000-0002-7157-5683

Ezekiel Quittner-Strom (E)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT 84112.
ORCID: 0000-0002-0250-3475

Yi Zhu (Y)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
ORCID: 0000-0003-1650-1363

Kamrul H Chowdhury (KH)

Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT 84112.

Zhuzhen Zhang (Z)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
ORCID: 0000-0001-6787-3920

Shangang Zhao (S)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
ORCID: 0000-0002-9209-8206

Na Li (N)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.

Reshing Ye (R)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.

Young Lee (Y)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Medical Service, Veterans Administration North Texas Health Care System, Dallas, TX 75216.

Yiyi Zhang (Y)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.

Shiuhwei Chen (S)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.

Xinxin Yu (X)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Medical Service, Veterans Administration North Texas Health Care System, Dallas, TX 75216.

Derek C Leonard (DC)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.

Greg Poffenberger (G)

Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232.
ORCID: 0000-0002-7363-4683

Alison Von Deylen (A)

Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232.
ORCID: 0000-0002-9678-4393

S Kay McCorkle (SK)

Medical Service, Veterans Administration North Texas Health Care System, Dallas, TX 75216.

Amnon Schlegel (A)

Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT 84112.
Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112.
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.
ORCID: 0000-0003-4060-2252

Kyle W Sloop (KW)

Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.

Alexander M Efanov (AM)

Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
ORCID: 0000-0002-8630-1503

Ruth E Gimeno (RE)

Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.

Philipp E Scherer (PE)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
ORCID: 0000-0003-0680-3392

Alvin C Powers (AC)

Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232.
Veterans Administration, Tennessee Valley Healthcare System, Nashville, TN 37212.
ORCID: 0000-0003-1941-5786

Roger H Unger (RH)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Medical Service, Veterans Administration North Texas Health Care System, Dallas, TX 75216.

William L Holland (WL)

Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549; will.holland@hsc.utah.edu.
Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT 84112.
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Glycémie › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Peptide C › Glucagon blockade restores functional β-cell...
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questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Diabète de type 1 › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Glucagon › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules entéroendocrines › Cellules à glucagon › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Insuline › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules entéroendocrines › Cellules à insuline › Glucagon blockade restores functional β-cell...
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questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation d'ilots de Langerhans › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › Glucagon blockade restores functional β-cell...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Taille d'organe › Glucagon blockade restores functional β-cell...
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