Diminished Fraction of Blockable ATP-Sensitive K+ Channels in Islets Transplanted Into Diabetic Mice

Autor: Franz Martín, Eduard Montana, Bernat Soria, Víctor Nacher, Etelvina Andreu, Juan Vicente Sánchez-Andrés
Přispěvatelé: Universitat de Barcelona, Ministerio de Sanidad y Consumo (España), European Commission, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Dirección General de Investigación Científica y Técnica, DGICT (España)
Rok vydání: 1996
Předmět:
Male
Potassium Channels
Adenosine
endocrine system diseases
Physiology
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Adenosina
Islets of Langerhans Transplantation
Membrane Potentials
Mice
Adenosine Triphosphate
Cytosol
Membrane potential
Diabetis
geography.geographical_feature_category
Illots de Langerhans
Diabetes
Islet
medicine.drug
Farmacologia
endocrine system
medicine.medical_specialty
Tolbutamide
Fisiologia
chemistry.chemical_element
Islands of Langerhans
Biology
Calcium
Diabetes Mellitus
Experimental
Potassium channels
Islets of Langerhans
Canals de potassi
Diabetes mellitus
Internal medicine
Internal Medicine
medicine
Animals
Pharmacology
geography
Cirurgia
Insulin
medicine.disease
Mice
Inbred C57BL
Transplantation
Glucose
Endocrinology
chemistry
Carbachol
Surgery
Secretagogue
Zdroj: Recercat. Dipósit de la Recerca de Catalunya
instname
Dipòsit Digital de la UB
Universidad de Barcelona
Digital.CSIC. Repositorio Institucional del CSIC
ISSN: 1939-327X
0012-1797
DOI: 10.2337/diab.45.12.1755
Popis: The reasons for the poor outcome of islet transplantation in diabetic patients are not well known; a better understanding of the pathophysiology of transplanted islets is needed. To study the mechanism coupling secretagogue stimuli with insulin release in transplanted islets, we determined the effects of glucose, tolbutamide, and carbamylcholine on the beta-cell membrane potential and cytosolic calcium concentrations ([Ca2+]i) of islets syngeneically transplanted into normal and streptozocin-induced diabetic mice. In both groups, normoglycemia was maintained after transplantation. Islets transplanted into normal recipients showed similar changes in beta-cell membrane potential and [Ca2+]i oscillations to those in control islets. In contrast, when islets were transplanted into diabetic mice, bursts of electrical activity were triggered at lower glucose concentrations (5.6 mmol/l) than in control islets (11 mmol/l), and maximal electrical activity was achieved at lower glucose concentrations (11 mmol/l) than in control islets (22 mmol/l). When membrane potential was plotted as a function of glucose concentration, the dose-response curve was shifted to the left. Compared with control islets, glucose-induced [Ca2+]i oscillations were broader in duration (22.3 +/- 0.6 s vs. 118.1 +/- 12.6 s; P < 0.01) and higher in amplitude (135 +/- 36 nmol/l vs. 352 +/- 36 nmol/l; P < 0.01). Glucose supersensitivity was attributed to a resting decrease in the fraction of blockable ATP-sensitive K+ (K+(ATP)) channels in transplanted islets that maintained normoglycemia with a limited beta-cell mass
This work was partially supported by grants FIS 93/0329 (E.M.) and FIS 94-0014-01 (B.S.) from the Ministry of Health of Spain and Contract ERBSC1-CT 92083 from the Commission of the European Union. V. Nacher and E. Andreu were the recipients of fellowships from Fundacid August Pi i Sunyer and DGICYT, respectively.
Databáze: OpenAIRE
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