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Insulin inhibits gl...
Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion
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Vergari, Elisa (author)
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Knudsen, Jakob G (author)
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Ramracheya, Reshma (author)
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- Salehi, Albert (author)
- Gothenburg University,Göteborgs universitet,University of Gothenburg,Lund University,Lunds universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Zhang, Quan (author)
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Adam, Julie (author)
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- Wernstedt Asterholm, Ingrid, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Benrick, Anna, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Briant, Linford J B (author)
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Chibalina, Margarita V (author)
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Gribble, Fiona M (author)
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- Hamilton, Alexander (author)
- Lund University,Lunds universitet,Churchill Hospital
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Hastoy, Benoit (author)
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Reimann, Frank (author)
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Rorsman, Nils J G (author)
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Spiliotis, Ioannis I (author)
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Tarasov, Andrei (author)
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- Wu, Yanling, 1985 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Ashcroft, Frances M. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Rorsman, Patrik, 1959 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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(creator_code:org_t)
- 2019-01-11
- 2019
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Abstract
Subject headings
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- Hypoglycaemia (low plasma glucose) is a serious and potentially fatal complication of insulin-treated diabetes. In healthy individuals, hypoglycaemia triggers glucagon secretion, which restores normal plasma glucose levels by stimulation of hepatic glucose production. This counterregulatory mechanism is impaired in diabetes. Here we show in mice that therapeutic concentrations of insulin inhibit glucagon secretion by an indirect (paracrine) mechanism mediated by stimulation of intra-islet somatostatin release. Insulin's capacity to inhibit glucagon secretion is lost following genetic ablation of insulin receptors in the somatostatin-secreting δ-cells, when insulin-induced somatostatin secretion is suppressed by dapagliflozin (an inhibitor of sodium-glucose co-tranporter-2; SGLT2) or when the action of secreted somatostatin is prevented by somatostatin receptor (SSTR) antagonists. Administration of these compounds in vivo antagonises insulin's hypoglycaemic effect. We extend these data to isolated human islets. We propose that SSTR or SGLT2 antagonists should be considered as adjuncts to insulin in diabetes therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Animals
- Benzhydryl Compounds/pharmacology
- Blood Glucose/analysis
- Diabetes Mellitus/drug therapy
- Female
- Glucagon/metabolism
- Glucagon-Secreting Cells/drug effects
- Glucosides/pharmacology
- Humans
- Hypoglycemia/pathology
- Insulin/metabolism
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Receptor, Insulin/genetics
- Receptors, Somatostatin/antagonists & inhibitors
- Sodium-Glucose Transporter 2/metabolism
- Sodium-Glucose Transporter 2 Inhibitors/pharmacology
- Somatostatin/metabolism
- pancreatic beta-cells
- antagonism improves glucagon
- gated ion channels
- delta-cells
- counterregulatory responses
- cellular perfusion
- alpha
- receptor
- dapagliflozin
- hypoglycemia
- Science & Technology - Other Topics
- agner ji
- 1988
- diabetes
- v37
- p1715
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Vergari, Elisa
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Knudsen, Jakob G
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Ramracheya, Resh ...
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Salehi, Albert
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Zhang, Quan
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Adam, Julie
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show more...
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Wernstedt Asterh ...
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Benrick, Anna, 1 ...
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Briant, Linford ...
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Chibalina, Marga ...
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Gribble, Fiona M
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Hamilton, Alexan ...
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Hastoy, Benoit
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Reimann, Frank
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Rorsman, Nils J ...
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Spiliotis, Ioann ...
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Tarasov, Andrei
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Wu, Yanling, 198 ...
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Ashcroft, France ...
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Rorsman, Patrik, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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University of Gothenburg