Association of upregulated activity of KATPchannels with impaired insulin secretion in UCP1‐expressing insulinoma cells
| Autor: | Nobuyuki Koriyama, Toshihiko Yada, Mitsuhiro Nakazaki, Yoshitomo Oka, Katsumi Aso, Masafumi Kakei, Chuwa Tei, Michiyo Fukudome, Hisamitsu Ishihara, Hiroshi Hashiguchi |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Potassium Channels Physiology Tolbutamide Biology Carbohydrate metabolism Ion Channels Membrane Potentials Mitochondrial Proteins Mice Adenosine Triphosphate Cytosol Downregulation and upregulation Internal medicine Insulin Secretion Tumor Cells Cultured medicine Animals Insulin Patch clamp Insulinoma Uncoupling Protein 1 Ion channel Membrane potential Membrane Proteins medicine.disease Research Papers Potassium channel Mitochondria Gene Expression Regulation Neoplastic Pancreatic Neoplasms Glucose Endocrinology Calcium Carrier Proteins medicine.drug |
| Zdroj: | The Journal of Physiology. 540:781-789 |
| ISSN: | 1469-7793 0022-3751 |
| DOI: | 10.1113/jphysiol.2001.013048 |
| Popis: | Insulin-secreting MIN6 cells overexpressing uncoupling protein-1 (UCP1) were studied regarding insulin secretion in response to various secretagogues. Overexpression of UCP1 prevented an increase of cytosolic ATP levels induced by glucose. In contrast, glucose utilization was not affected, nor was glycerol phosphate flux. The UCP1-expressing cells showed an inability to increase cytosolic Ca(2+) concentration ([Ca(2+)](i)) in response to glucose or alpha ketoisocaproate and this resulted in less insulin secretion, whereas initial reduction in [Ca(2+)](i) occurring upon either nutrient addition was not affected. Moreover, the effectiveness of tolbutamide on [Ca(2+)](i) increase was reduced and the dose-response relations for insulin secretion induced by the agent was shifted toward the right in the UCP1-expressing cells. The resting membrane potential of the UCP1-expressing cells was significantly hyperpolarized by 6.2 mV compared with control cells. In the perforated and conventional whole-cell patch-clamp configurations, the conductance density of ATP-sensitive K(+) (K(ATP)) channels of the UCP1-expressing cells was 6-fold and 1.7-fold greater than that of the control cells, respectively. The sensitivity of K(ATP) channels for tolbutamide was not different between two groups, indicating that in intact cells more than 6-fold higher concentrations of tolbutamide were required to reduce the K(ATP) channel currents of UCP1-expressing cells to the same levels as of the control cells. The current density of the voltage-dependent Ca(2+) channels was not influenced. In conclusion, UCP1-expressing cells showed a refractoriness to respond to tolbutamide as well as nutrients. An upregulated activity of K(ATP) channels was associated with unresponsiveness to the agent in the cells with impaired mitochondrial function. |
| Databáze: | OpenAIRE |
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