Effect of glucose/sulfonylurea interaction on release of insulin, glucagon, and somatostatin from isolated perfused rat pancreas.

Efendić, Suad; Enzmann, F.; Nylén, A.; Uvnäs‐Wallensten, Kerstin; Luft, Rolf

doi:10.1073/pnas.76.11.5901

Cited by 67 publications

(50 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While it is well established that hyperglycemia suppresses glucagon secretion strongly, the effect of sulfonylurea on glucagon secretion is controversial and reported to be unaffected (17), stimulated (38), inhibited (39), and influenced differently depending on the prevailing glucose and drug concentration and presence of paracrine effectors (38,40,41). We observed that during infusion with tolbutamide alone, glucagon secretion did not rise in the presence of 3 mmol/l glucose.…”

Section: Discussionmentioning

confidence: 49%

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

2007

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 49%

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

2007

View full text Add to dashboard Cite

show abstract

“…There have only been a handful of studies investigating the mechanisms by which nutrients and pharmacological agents evoke somatostatin secretion from rodent delta cells [8][9][10] and even fewer data are available for human delta cells [11,12]. Here we have explored the control of glucose-induced somatostatin release from isolated human islets and characterised the membrane currents involved in delta cell electrical activity and exocytosis.…”

Section: Introductionmentioning

confidence: 99%

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

et al. 2009

View full text Add to dashboard Cite

Aims/hypothesis The aim of this study was to characterise electrical activity, ion channels, exocytosis and somatostatin release in human delta cells/pancreatic islets. Methods Glucose-stimulated somatostatin release was measured from intact human islets. Membrane potential, currents and changes in membrane capacitance (reflecting exocytosis) were recorded from individual human delta cells identified by immunocytochemistry. Results Somatostatin secretion from human islets was stimulated by glucose and tolbutamide and inhibited by diazoxide. Human delta cells generated bursting or sporadic electrical activity, which was enhanced by tolbutamide but unaffected by glucose. Delta cells contained a tolbutamide-insensitive, Ba 2+ -sensitive inwardly rectifying K + current and two types of voltagegated K + currents, sensitive to tetraethylammonium/ stromatoxin (delayed rectifying, Kv2.1/2.2) and 4-aminopyridine (A current). Voltage-gated tetrodotoxin (TTX)-sensitive Na + currents contributed to the action potential upstroke but TTX had no effect on somatostatin release. Delta cells are equipped with Ca 2+ channels blocked by isradipine (L), ω-agatoxin (P/Q) and NNC 55-0396 (T). Blockade of any of these channels interferes with delta cell electrical activity and abolishes glucose-stimulated somatostatin release. Capacitance measurements revealed a slow component of depolarisation-evoked exocytosis sensitive to ω-agatoxin. Conclusions/interpretation Action potential firing in delta cells is modulated by ATP-sensitive K + -channel activity. The membrane potential is stabilised by Ba 2+ -sensitive inwardly rectifying K + channels. Voltage-gated L-and T-type Ca 2+ channels are required for electrical activity, whereas Na + currents and P/Q-type Ca 2+ channels contribute to (but are not necessary for) the upstroke of the action potential. Action potential repolarisation is mediated by A-type and Kv2.1/2.2 K + channels. Exocytosis is tightly linked to Ca 2+ -influx via P/Q-type Ca 2+ channels. Glucose stimulation of somatostatin secretion involves both K ATP channel-dependent and -independent processes.

show abstract

“…In addition, we wished to investigate how blocking of delta cell action might influence the effect of GIP and glucose on glucagon secretion, given the fact that GIP and glucose, like GLP-1, have been reported to stimulate pancreatic somatostatin secretion [28][29][30][31][32]. As a model, we used the isolated perfused rat pancreas, in which the integrity of the islet's cytoarchitecture and microvasculature is preserved, which is crucial when investigating paracrine interactions between islet cells.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis The glucose-lowering effect of glucagonlike peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but also on its ability to restrain glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide (GIP) stimulates glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits glucagon secretion, is involved in this divergent behaviour. Methods At 1.5 mmol/l glucose and therefore minimal insulin secretion, the glucagon, insulin and somatostatin responses to 20 mmol/l glucose, GLP-1, GIP and somatostatin were studied in the presence of a high-affinity monoclonal somatostatin antibody and of a highly specific somatostatin receptor subtype 2 (SSTR2) antagonist (PRL-2903) in the isolated perfused rat pancreas. Results In control experiments, GLP-1 at 1 and 10 nmol/l reduced glucagon secretion significantly to 59.0±6.3% (p<0.004; n=5; SSTR2 series; each vs pre-infusion level) and to 48.0±2.6% (p<0.001; n=6; somatostatin antibody series) respectively. During somatostatin antibody administration, GLP-1 still inhibited glucagon secretion significantly, but the effect was less pronounced than in control experiments (p<0.018). Co-infusion of the SSTR2 antagonist completely abolished the GLP-1-induced suppression of glucagon secretion. In contrast, neither the GIP-induced stimulation of glucagon release nor its inhibition by 20 mmol/l glucose was altered by somatostatin antibody or SSTR2 antagonist administration. Conclusions/interpretationWe conclude that GLP-1 is capable of inhibiting glucagon secretion even in the absence of secretory products from the beta cell. It is highly likely that this is mediated via somatostatin interacting with SSTR2 on rat alpha cells. In contrast, GIP and glucose seem to influence the alpha cell independently of somatostatin secretion.

show abstract

Effect of glucose/sulfonylurea interaction on release of insulin, glucagon, and somatostatin from isolated perfused rat pancreas.

Cited by 67 publications

References 15 publications

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells

Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas

Contact Info

Product

Resources

About