ArticleMolecular metabolism2015
LKB1 and AMPKα1 are required in pancreatic alpha cells for the normal regulation of glucagon secretion and responses to hypoglycemia.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Transcriptomics of SGLT2-positive early proximal tubule segments in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism.American journal of physiology. Renal physiology · 2025Article
- Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025Review
- Metabolic regulation of glucagon secretion.The Journal of endocrinology · 2023Article
- Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.Frontiers in endocrinology · 2021Article
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
- The Glucagon-Like Adipokinetic Hormone inFrontiers in physiology · 2021Review
- Mechanisms of the Regulation and Dysregulation of Glucagon Secretion.Oxidative medicine and cellular longevity · 2020Review
- The Central Role of Glucokinase in Glucose Homeostasis: A Perspective 50 Years After Demonstrating the Presence of the Enzyme in Islets of Langerhans.Frontiers in physiology · 2019Review
- The α-cell in diabetes mellitus.Nature reviews. Endocrinology · 2018Review
- Pancreatic alpha cell-selective deletion of Tcf7l2 impairs glucagon secretion and counter-regulatory responses to hypoglycaemia in mice.Diabetologia · 2017Article
- High-fidelityMolecular metabolism · 2017Article
- Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.Biochimica et biophysica acta · 2016Review
- Deletion of Lkb1 in adult mice results in body weight reduction and lethality.Scientific reports · 2016Article
- Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production.Diabetologia · 2016Article
- Glucose control of glucagon secretion-'There's a brand-new gimmick every year'.Upsala journal of medical sciences · 2016Review
- Molecular Genetic Regulation of Slc30a8/ZnT8 Reveals a Positive Association With Glucose Tolerance.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.PloS one · 2016Article
- Limited impact on glucose homeostasis of leptin receptor deletion from insulin- or proglucagon-expressing cells.Molecular metabolism · 2015Article
- The Zinc Transporter Slc30a8/ZnT8 Is Required in a Subpopulation of Pancreatic α-Cells for Hypoglycemia-induced Glucagon Secretion.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
aims/hypothesisGlucagon release from pancreatic alpha cells is required for normal glucose homoeostasis and is dysregulated in both Type 1 and Type 2 diabetes. The tumour suppressor LKB1 (STK11) and the downstream kinase AMP-activated protein kinase (AMPK), modulate cellular metabolism and growth, and AMPK is an important target of the anti-hyperglycaemic agent metformin. While LKB1 and AMPK have emerged recently as regulators of beta cell mass and insulin secretion, the role of these enzymes in the control of glucagon production in vivo is unclear.
methodsHere, we ablated LKB1 (αLKB1KO), or the catalytic alpha subunits of AMPK (αAMPKdKO, -α1KO, -α2KO), selectively in ∼45% of alpha cells in mice by deleting the corresponding flox'd alleles with a preproglucagon promoter (PPG) Cre.
resultsBlood glucose levels in male αLKB1KO mice were lower during intraperitoneal glucose, aminoimidazole carboxamide ribonucleotide (AICAR) or arginine tolerance tests, and glucose infusion rates were increased in hypoglycemic clamps (p < 0.01). αLKB1KO mice also displayed impaired hypoglycemia-induced glucagon release. Glucose infusion rates were also elevated (p < 0.001) in αAMPKα1 null mice, and hypoglycemia-induced plasma glucagon increases tended to be lower (p = 0.06). Glucagon secretion from isolated islets was sensitized to the inhibitory action of glucose in αLKB1KO, αAMPKdKO, and -α1KO, but not -α2KO islets. CONCLUSIONS/
interpretationAn LKB1-dependent signalling cassette, involving but not restricted to AMPKα1, is required in pancreatic alpha cells for the control of glucagon release by glucose.
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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 OpenQuestion graph.