We have used the whole-cell recording technique to determine whether ATP-sensitive potassium (KATP) currents, voltage-dependent Ca2+ currents, and exocytosis are different in single β-cells from pancreatic islets of Goto-Kakizaki (GK) rats, a novel model of NIDDM, and normal rats. In addition, we have also measured the insulin secretory responses, ATP content, and the rate of glucose metabolism in intact islets. Although the glucose sensitivity of the KATP current was similar between GK rats and controls, in the absence of glucose, KATP current density was larger in GK rats, which resulted in a more hyperpolarized membrane potential. Whole-cell Ca2+ currents were similar. By monitoring the cell capacitance with a fixed intracellular solution, no difference was detected in the exocytotic responses of β-cells from normal and GK rats. In islets from GK rats, the rates of glucose utilization ([3H]H2O production from 5-[3H]glucose) and oxidation ([14C]CO2 production from U-[14C]glucose) were not significantly different from controls. Insulin secretion, however, was impaired (by 50%), and this was paralleled by a smaller increase in ATP content in response to stimulation by 10 mmol/1 glucose in islets from GK rats when compared with controls. Under conditions in which KATP channels were held open and the effects of glucose were independent of membrane potential, insulin release was still significantly lower in GK rat islets than in controls. These findings suggest that the impaired insulin secretion in islets from GK rats does not simply result from a failure to close KATP channels, nor does it result from an impairment in calcium secretion coupling.
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Islet Studies|
January 01 1998
Electrophysiological and Metabolic Characterization of Single β-Cells and Islets From Diabetic GK Rats
S J Hughes;
S J Hughes
Department of Physiology, Division of Basic Medical Science, Imperial College School of Medicine at St. Mary's
London
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M Faehling;
M Faehling
Department of Physiology, University of Oxford
Oxford, England, U.K.
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C W Thorneley;
C W Thorneley
Department of Physiology, Division of Basic Medical Science, Imperial College School of Medicine at St. Mary's
London
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P Proks;
P Proks
Institute of Molecular Physiology and Genetics
Bratislava, Slovakia
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F M Ashcroft;
F M Ashcroft
Department of Physiology, University of Oxford
Oxford, England, U.K.
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P A Smith
P A Smith
Department of Physiology, University of Oxford
Oxford, England, U.K.
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Address correspondence and reprint requests to P.A. Smith, the Department of Physiology, University of Oxford, South Parks Rd., Oxford, OX1 3PT U.K. E-mail: [email protected]
Diabetes 1998;47(1):73–81
Article history
Received:
December 16 1996
Revision Received:
September 10 1997
Accepted:
September 10 1997
PubMed:
9421377
Citation
S J Hughes, M Faehling, C W Thorneley, P Proks, F M Ashcroft, P A Smith; Electrophysiological and Metabolic Characterization of Single β-Cells and Islets From Diabetic GK Rats. Diabetes 1 January 1998; 47 (1): 73–81. https://doi.org/10.2337/diab.47.1.73
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