Anders Tengholm
Physiology of pancreatic islet hormone secretion
The research in our group aims at clarifying the mechanisms that regulate the release of insulin, glucagon, somatostatin as well as other peptides and secretory factors from the islets of Langerhans. Insulin promotes uptake and storage of glucose and other sources of energy in liver, muscle and fat cells following meal ingestion, while the main function of glucagon is to mobilize glucose to prevent potentially life-threatening hypoglycaemia during fasting. Insufficient secretion of insulin and dysregulated secretion of glucagon are hallmarks of diabetes but the underlying mechanisms are poorly understood. Elucidation of the molecular and cellular physiology of islet hormone secretion and the malfunctions causing diabetes may provide new strategies for treatment and prevention of the disease.
By combining biochemical and molecular biology techniques with fluorescent cell signalling biosensors and live-cell imaging methods, we study the spatio-temporal dynamics of signalling processes that regulate secretion in single cells and intact mouse and human pancreatic islets. We are particularly interested in how the islet cells sense environmental stimuli and translate them into altered rates of hormone release and how the intra- and intercellular signalling is organized to generate an appropriate time-course of hormone secretion.
Group members
Publications
Mechanistic insights and approaches for beta cell regeneration
Part of Nature Chemical Biology, 2025
Insulin release from isolated cat islets of Langerhans
Part of Domestic Animal Endocrinology, 2024
- DOI for Insulin release from isolated cat islets of Langerhans
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RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function
Part of Diabetologia, p. 1642-1662, 2024
- DOI for RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function
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Part of Cell Reports, 2024
- DOI for OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion
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Bo Hellman, 19 June 1930-4 December 2023
Part of Diabetologia, p. 1165-1167, 2024
Part of Cellular Signalling, 2023
- DOI for Indicator-dependent differences in detection of local intracellular Ca2+release events evoked by voltage-gated Ca2+entry in pancreatic & beta;-cells
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Part of Nature Biotechnology, p. 1042-1055, 2022
- DOI for Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
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Part of Acta Physiologica, 2021
- DOI for Glucose-induced cAMP elevation in β-cells involves amplification of constitutive and glucagon-activated GLP-1 receptor signalling
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Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion
Part of Molecular Metabolism, 2021
Part of Proceedings of the National Academy of Sciences of the United States of America, p. 2484-2495, 2020
- DOI for In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis
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γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion
Part of Journal of Biological Chemistry, 2020
- DOI for γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion
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Metabolic regulation of calcium signaling in beta cells
Part of Seminars in Cell and Developmental Biology, p. 20-30, 2020
Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes.
Part of Nature Communications, 2020
- DOI for Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes.
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Part of The FASEB Journal, p. 88-100, 2019
Part of Diabetes, p. 747-760, 2019
Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis
Part of eLIFE, 2019
- DOI for Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis
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Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
Part of Diabetologia, p. 1212-1224, 2019
- DOI for Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
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A membrane permeable prodrug of S223 for selective Epac2 activation in living cells
Part of Cells, 2019
- DOI for A membrane permeable prodrug of S223 for selective Epac2 activation in living cells
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Temporal Dynamics of VEGFA-Induced VEGFR2/FAK Co-Localization Depend on SHB
Part of Cells, 2019
- DOI for Temporal Dynamics of VEGFA-Induced VEGFR2/FAK Co-Localization Depend on SHB
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Cyclic AMP links glucose stimulation to somatostatin secretion in delta-cells
Part of The Journal of General Physiology, p. 1062-1065, 2019
A genetically encoded low-affinity Ca2+ sensor unmasks autocrine purinergic signalling in beta cells
Part of Diabetologia, 2018
Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells
Part of EBioMedicine, 2018
- DOI for Functional Characterization of Native, High-Affinity GABAA Receptors in Human Pancreatic β Cells
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cAMP signalling in insulin and glucagon secretion
Part of Diabetes, obesity and metabolism, p. 42-53, 2017
Recruitment of Epac2A to Insulin Granule Docking Sites Regulates Priming for Exocytosis
Part of Diabetes, p. 2610-2622, 2017
Part of Diabetologia, 2016
Glucose lowers cAMP to inhibit glucagon secretion by a direct effect on alpha cells
Part of Diabetologia, 2016
Part of Journal of Biological Chemistry, p. 14986-14995, 2016
- DOI for Autocrine Signaling Underlies Fast Repetitive Plasma Membrane Translocation of Conventional and Novel Protein Kinase C Isoforms in beta Cells
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Part of Diabetologia, p. 1928-1937, 2016
Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes
Part of Cell Metabolism, p. 1067-1077, 2016
Fluorescent protein vectors for pancreatic islet cell identification in live-cell imaging
Part of Pflügers Archiv, p. 1765-1777, 2016
- DOI for Fluorescent protein vectors for pancreatic islet cell identification in live-cell imaging
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CART is a novel glucose-dependent peptide with antidiabetic actions in humans
Part of Diabetologia, 2015
Paradoxical Ca2+ kinetics in islet-located glucagon-releasing alpha cells
Part of Diabetologia, 2015
Imaging sub-plasma membrane cAMP dynamics with fluorescent translocation reporters
Part of cAMP Signaling, p. 85-101, Springer-Verlag New York, 2015
- DOI for Imaging sub-plasma membrane cAMP dynamics with fluorescent translocation reporters
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Part of Diabetes, p. 904-915, 2015
- DOI for Impaired cAMP generation contributes to defective glucose-stimulated insulin secretion after long-term exposure to palmitate
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Submembrane ATP and Ca2+ kinetics in alpha-cells: unexpected signaling for glucagon secretion
Part of The FASEB Journal, p. 3379-3388, 2015
Submembrane ATP and Ca2+ kinetics in α‑cells: unexpected signaling for glucagon secretion
Part of The FASEB Journal, p. 3379-3388, 2015
Part of Diabetes/Metabolism Research Reviews, p. 9-10, 2015
Part of American Journal of Physiology - Gastrointestinal and Liver Physiology, 2015
Part of Diabetologia, 2014
Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets
Part of Journal of Endocrinology, p. 267-275, 2014
- DOI for Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets
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Neurotransmitter control of islet hormone pulsatility
Part of Diabetes, obesity and metabolism, p. 102-110, 2014
Purinergic P2Y1 receptors take centre stage in autocrine stimulation of human beta cells
Part of Diabetologia, p. 2436-2439, 2014
- DOI for Purinergic P2Y1 receptors take centre stage in autocrine stimulation of human beta cells
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Part of Diabetologia, 2013
Part of Diabetologia, 2013
Functional differences between aggregated and dispersed insulin-producing cells
Part of Diabetologia, p. 1557-1568, 2013
- DOI for Functional differences between aggregated and dispersed insulin-producing cells
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Part of Diabetologia, p. 1577-1586, 2013
- DOI for Oscillations of sub-membrane ATP in glucose-stimulated beta cells depend on negative feedback from Ca2+
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Part of Cellular Signalling, p. 85-92, 2013
- DOI for Aberrant association between vascular endothelial growth factor receptor-2 and VE-cadherin in response to vascular endothelial growth factor-a in Shb-deficient lung endothelial cells
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DNA Methylation of Alternative Promoters Directs Tissue Specific Expression of Epac2 Isoforms
Part of PLOS ONE, 2013
- DOI for DNA Methylation of Alternative Promoters Directs Tissue Specific Expression of Epac2 Isoforms
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The role of mechanical force and ROS in integrin-dependent signals
Part of PLOS ONE, 2013
- DOI for The role of mechanical force and ROS in integrin-dependent signals
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Part of Diabetologia, p. 1327-1338, 2013
- DOI for Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl
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