Paradoxical stimulation of glucagon secretion by high glucose concentrations [Elektronisk resurs]
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Salehi, Albert (författare)
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Vieira, Elaine (författare)
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Gylfe, Erik (författare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
- 2006
- Engelska.
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Ingår i: Diabetes. - 0012-1797. ; 55:8, 2318-2323
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Sammanfattning
Ämnesord
Stäng
- Hypersecretion of glucagon contributes to the dysregulation of glucose homeostasis in diabetes. To clarify the underlying mechanism, glucose-regulated glucagon secretion was studied in mouse pancreatic islets and clonal hamster In-R1-G9 glucagon-releasing cells. Apart from the well-known inhibition of secretion with maximal effect around 7 mmol/l glucose, we discovered that mouse islets showed paradoxical stimulation of glucagon release at 25-30 mmol/l and In-R1-G9 cells at 12-20 mmol/l sugar. Whereas glucagon secretion in the absence of glucose was inhibited by hyperpolarization with diazoxide, this agent tended to further enhance secretion stimulated by high concentrations of the sugar. Because U-shaped dose-response relationships for glucose-regulated glucagon secretion were observed in normal islets and in clonal glucagon-releasing cells, both the inhibitory and stimulatory components probably reflect direct effects on the a-cells. Studies of isolated mouse a-cells indicated that glucose inhibited glucagon secretion by lowering the cytoplasmic Ca2+ concentration. However, stimulation of glucagon release by high glucose concentrations did not require elevation of Ca2+, indicating involvement of novel mechanisms in glucose regulation of glucagon secretion. A U-shaped dose-response relationship for glucose-regulated glucagon secretion may explain why diabetic patients with pronounced hyperglycemia display paradoxical hyperglucagonemia.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Cell and Molecular Biology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Cell- och molekylärbiologi (hsv)
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Endocrinology and Diabetes (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Endokrinologi och diabetes (hsv)
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Physiology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Fysiologi (hsv)
- MEDICINE (svep)
- Morphology, cell biology, pathology (svep)
- Cell biology (svep)
- MEDICIN (svep)
- Morfologi, cellbiologi, patologi (svep)
- Cellbiologi (svep)
- MEDICINE (svep)
- Dermatology and venerology,clinical genetics, internal medicine (svep)
- Internal medicine (svep)
- Diabetology (svep)
- MEDICIN (svep)
- Dermatologi och venerologi, klinisk genetik, invärtesmedicin (svep)
- Invärtesmedicin (svep)
- Diabetologi (svep)
- MEDICINE (svep)
- Physiology and pharmacology (svep)
- Physiology (svep)
- MEDICIN (svep)
- Fysiologi och farmakologi (svep)
- Fysiologi (svep)
- Medical Cell Biology (uu)
- Medicinsk cellbiologi (uu)
Indexterm och SAB-rubrik
- [Ca2+]i
- cytoplasmic Ca2+ concentration
- KATP channel
- ATP-sensitive K+ channel
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