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

Group members: Heléne Dansk, Oleg Dyachok, Erik Gylfe, Ylva Hellman, Bryon Hughson, Kousik Mandal, Moa Södergren, Anders Tengholm, Yunjian Xu, Mingyu Yang

Publications

Insulin release from isolated cat islets of Langerhans

Strage, Emma M.; Ley, Cecilia; Westermark, Gunilla T.; Tengholm, Anders

Part of Domestic Animal Endocrinology, 2024
- DOI for Insulin release from isolated cat islets of Langerhans
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OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion

Panagiotou, Styliani; Tan, Kia Wee; Nguyen, Phuoc My; Mueller, Andreas et al.

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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Indicator-dependent differences in detection of local intracellular Ca2+release events evoked by voltage-gated Ca2+entry in pancreatic & beta;-cells

Yang, Mingyu; Dyachok, Oleg; Xu, Yunjian; Gylfe, Erik et al.

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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Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.

Balboa, Diego; Barsby, Tom; Lithovius, Väinö; Saarimäki-Vire, Jonna et al.

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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Glucose-induced cAMP elevation in β-cells involves amplification of constitutive and glucagon-activated GLP-1 receptor signalling

Shuai, Hongyan; Xu, Yunjian; Ahooghalandari, Parvin; Tengholm, Anders

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

Vishnu, N.; Hamilton, A.; Bagge, A.; Wernersson, A. et al.

Part of Molecular Metabolism, 2021
- DOI for Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion
In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis

Petrenko, Volodymyr; Gandasi, Nikhil; Sage, Daniel; Tengholm, Anders et al.

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

Yu, Qian; Lai, Bao Khanh; Ahooghalandari, Parvin; Helander, Anders et al.

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

Idevall Hagren, Olof; Tengholm, Anders

Part of Seminars in Cell and Developmental Biology, p. 20-30, 2020
- DOI for Metabolic regulation of calcium signaling in beta cells
Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes.

Omar-Hmeadi, Muhmmad; Lund, Per-Eric; Gandasi, Nikhil; Tengholm, Anders et al.

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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ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells

Wang, Xuan; Jiang, Lin; Wallerman, Ola; Younis, Shady et al.

Part of The FASEB Journal, p. 88-100, 2019
- DOI for ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells
The Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 is Essential for Proinsulin Handling

Mojtaba Ghiasi, Seyed; Dahlby, Tina; Hede Andersen, Caroline; Haataja, Leena et al.

Part of Diabetes, p. 747-760, 2019
- DOI for The Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 is Essential for Proinsulin Handling
Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis

Gucek, Alenka; Gandasi, Nikhil R; Omar-Hmeadi, Muhmmad; Bakke, Marit et al.

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

Yu, Qian; Shuai, Hongyan; Ahooghalandari, Parvin; Gylfe, Erik et al.

Part of Diabetologia, p. 1212-1224, 2019
- DOI for Glucose controls glucagon secretion by directly modulating cAMP in alpha cells
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Cyclic AMP links glucose stimulation to somatostatin secretion in delta-cells

Tengholm, Anders

Part of The Journal of General Physiology, p. 1062-1065, 2019
- DOI for Cyclic AMP links glucose stimulation to somatostatin secretion in delta-cells
A membrane permeable prodrug of S223 for selective Epac2 activation in living cells

Xu, Yunjian; Schwede, Frank; Wienk, Hans; Tengholm, Anders et al.

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

Pietilä, Ilkka; van Mourik, Djenolan; Tamelander, Andreas; Kriz, Vitezslav et al.

Part of Cells, 2019
- DOI for Temporal Dynamics of VEGFA-Induced VEGFR2/FAK Co-Localization Depend on SHB
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A genetically encoded low-affinity Ca2+ sensor unmasks autocrine purinergic signalling in beta cells

Yang, Mingyu; Idevall-Hagren, Olof; Gylfe, Erik; Tengholm, Anders

Part of Diabetologia, 2018
Functional Characterization of Native, High-Affinity GABA_A Receptors in Human Pancreatic β Cells

Korol, Sergiy V; Jin, Zhe; Jin, Yang; Bhandage, Amol K. et al.

Part of EBioMedicine, 2018
- DOI for Functional Characterization of Native, High-Affinity GABA_A Receptors in Human Pancreatic β Cells
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cAMP signalling in insulin and glucagon secretion

Tengholm, Anders; Gylfe, Erik

Part of Diabetes, obesity and metabolism, p. 42-53, 2017
- DOI for cAMP signalling in insulin and glucagon secretion
Recruitment of Epac2A to Insulin Granule Docking Sites Regulates Priming for Exocytosis

Alenkvist, Ida; Gandasi, Nikhil R; Barg, Sebastian; Tengholm, Anders

Part of Diabetes, p. 2610-2622, 2017
- DOI for Recruitment of Epac2A to Insulin Granule Docking Sites Regulates Priming for Exocytosis
ZBED6 negatively regulates insulin content, glucose-stimulated insulin secretion, neuronal differentiation and cell aggregation in MIN6 cells

Wang, Xuan; Jiang, L.; Wallerman, Ola; Yu, Qian et al.

Part of Diabetologia, 2016
Glucose lowers cAMP to inhibit glucagon secretion by a direct effect on alpha cells

Yu, Qian; Shuai, Hongyan; Ahooghalandari, Parvin; Gylfe, Erik et al.

Part of Diabetologia, 2016
Autocrine Signaling Underlies Fast Repetitive Plasma Membrane Translocation of Conventional and Novel Protein Kinase C Isoforms in beta Cells

Wuttke, Anne; Yu, Qian; Tengholm, Anders

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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CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

Abels, Mia; Riva, Matteo; Bennet, Hedvig; Ahlqvist, Emma et al.

Part of Diabetologia, p. 1928-1937, 2016
- DOI for CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion
Fluorescent protein vectors for pancreatic islet cell identification in live-cell imaging

Shuai, Hongyan; Xu, Yunjian; Yu, Qian; Gylfe, Erik et al.

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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Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes

Tuomi, Tiinamaija; Nagorny, Cecilia L. F.; Singh, Pratibha; Bennet, Hedvig et al.

Part of Cell Metabolism, p. 1067-1077, 2016
- DOI for Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes
CART is a novel glucose-dependent peptide with antidiabetic actions in humans

Abels, M.; Riva, M.; Poon, W.; Bennet, H. et al.

Part of Diabetologia, 2015
Paradoxical Ca2+ kinetics in islet-located glucagon-releasing alpha cells

Yu, Qian; Li, Jia; Ahooghalandari, Parvin; Tengholm, Anders et al.

Part of Diabetologia, 2015
Imaging sub-plasma membrane cAMP dynamics with fluorescent translocation reporters

Tengholm, Anders; Idevall-Hagren, Olof

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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Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide

Wan Saudi, Wan Salman; Halim, Mohammed Abdul; Gillberg, Linda; Rudholm-Feldreich, Tobias et al.

Part of American Journal of Physiology - Gastrointestinal and Liver Physiology, 2015
- DOI for Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide
Impaired cAMP generation contributes to defective glucose-stimulated insulin secretion after long-term exposure to palmitate

Tian, Geng; Sol, Eri Maria; Xu, Yunjian; Shuai, Hongyan et al.

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

Li, Jia; Yu, Qian; Ahooghalandari, Parvin; Gribble, Fiona M. et al.

Part of The FASEB Journal, p. 3379-3388, 2015
- DOI for Submembrane ATP and Ca2+ kinetics in alpha-cells: unexpected signaling for glucagon secretion
Submembrane ATP and Ca²⁺ kinetics in α‑cells: unexpected signaling for glucagon secretion

Li, Jia; Yu, Qian; Ahooghalandari, Parvin; Gribble, Fiona M et al.

Part of The FASEB Journal, p. 3379-3388, 2015
- DOI for Submembrane ATP and Ca²⁺ kinetics in α‑cells: unexpected signaling for glucagon secretion
Prolonged exposure to palmitate deteriorates glucose-induced cAMP generation and pulsatile insulin secretion

Tian, Geng; Tengholm, Anders

Part of Diabetes/Metabolism Research Reviews, p. 9-10, 2015
Paradoxical synchronisation of Ca2+ oscillations between alpha and beta cells within intact pancreatic islets

Yu, Qian; Li, Jia; Tengholm, Anders; Gylfe, Erik

Part of Diabetologia, 2014
Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets

Alenkvist, Ida; Dyachok, Oleg; Tian, Geng; Li, Jia et al.

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

Gylfe, Erik; Tengholm, Anders

Part of Diabetes, obesity and metabolism, p. 102-110, 2014
- DOI for Neurotransmitter control of islet hormone pulsatility
Purinergic P2Y1 receptors take centre stage in autocrine stimulation of human beta cells

Tengholm, Anders

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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Prolonged exposure to palmitate deteriorates glucose-induced cAMP generation and pulsatile insulin secretion

Tian, Geng; Sol, E. -RM.; Xu, Yunjian; Tengholm, Anders

Part of Diabetologia, 2013
Autocrine signals mediate plasma membrane translocation of protein kinase C in insulin-secreting cells

Tengholm, Anders; Wuttke, Anne

Part of Diabetologia, 2013
Functional differences between aggregated and dispersed insulin-producing cells

Chowdhury, Azazul Islam; Dyachok, Oleg; Tengholm, Anders; Sandler, Stellan et al.

Part of Diabetologia, p. 1557-1568, 2013
- DOI for Functional differences between aggregated and dispersed insulin-producing cells
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Oscillations of sub-membrane ATP in glucose-stimulated beta cells depend on negative feedback from Ca2+

Li, Jia; Shuai, Hongyan; Gylfe, Erik; Tengholm, Anders

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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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

Zang, Guangxiang; Christoffersson, Gustaf; Tian, Geng; Harun-Or-Rashid, Mohammad et al.

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

Hoivik, Erling A.; Witsoe, Solveig L.; Bergheim, Inger R.; Xu, Yunjian et al.

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

Zeller, Kathrin Stephanie; Riaz, Anjum; Sarve, Hamid; Li, Jia et al.

Part of PLOS ONE, 2013
- DOI for The role of mechanical force and ROS in integrin-dependent signals
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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

Mokhtari, Dariush; Al-Amin, Abdullah; Turpaev, Kyrill; Li, Tingting et al.

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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P2Y₁ receptor-dependent diacylglycerol signaling microdomains in β cells promote insulin secretion

Wuttke, Anne; Idevall-Hagren, Olof; Tengholm, Anders

Part of The FASEB Journal, p. 1610-1620, 2013
- DOI for P2Y₁ receptor-dependent diacylglycerol signaling microdomains in β cells promote insulin secretion
Spatial Control of Epac2 Activity by cAMP and Ca2+-Mediated Activation of Ras in Pancreatic beta Cells

Idevall-Hagren, Olof; Jakobsson, Ida; Xu, Yunjian; Tengholm, Anders

Part of Science Signaling, 2013
- DOI for Spatial Control of Epac2 Activity by cAMP and Ca2+-Mediated Activation of Ras in Pancreatic beta Cells
Role of phosphodiesterases in the shaping of sub-plasma-membrane cAMP oscillations and pulsatile insulin secretion

Tian, Geng; Sågetorp, Jenny; Xu, Yunjian; Shuai, Hongyan et al.

Part of Journal of Cell Science, p. 5084-5095, 2012
- DOI for Role of phosphodiesterases in the shaping of sub-plasma-membrane cAMP oscillations and pulsatile insulin secretion