Electrophysiological and metabolic characterization of single β-cells and islets from diabetic GK rats

被引:42
作者
Hughes, SJ
Faehling, M
Thorneley, CW
Proks, P
Ashcroft, FM
Smith, PA
机构
[1] Univ Oxford, Dept Physiol, Oxford OX1 3PT, England
[2] St Marys, Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept Physiol,Div Basic Med Sci, London, England
[3] Slovak Acad Sci, Inst Mol Physiol & Genet, SK-83334 Bratislava, Slovakia
基金
英国惠康基金;
关键词
D O I
10.2337/diabetes.47.1.73
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have used the whole-cell recording technique to determine whether ATP-sensitive potassium (K-ATP) currents, voltage-dependent Ca2+ currents, and exocytosis are different in single beta-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 K-ATP current was similar between GK rats and controls, in the absence of glucose, K-ATP 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 beta-cells from normal and GK rats. In islets from GK rats, the rates of glucose utilization ([H-3]H2O production from 5-[H-3]glucose) and oxidation ([C-14]CO2 production from U-[C-14]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/l glucose in islets from GK rats when compared with controls. Under conditions in which K-ATP 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 K-ATP channels, nor does it result from an impairment in calcium secretion coupling.
引用
收藏
页码:73 / 81
页数:9
相关论文
共 42 条
[1]   IMPACT OF DIABETIC INHERITANCE ON GLUCOSE-TOLERANCE AND INSULIN-SECRETION IN SPONTANEOUSLY DIABETIC GK-WISTAR RATS [J].
ABDELHALIM, SM ;
GUENIFI, A ;
LUTHMAN, H ;
GRILL, V ;
EFENDIC, S ;
OSTENSON, CG .
DIABETES, 1994, 43 (02) :281-288
[2]   EXOCYTOSIS ELICITED BY ACTION-POTENTIALS AND VOLTAGE-CLAMP CALCIUM CURRENTS IN INDIVIDUAL MOUSE PANCREATIC B-CELLS [J].
AMMALA, C ;
ELIASSON, L ;
BOKVIST, K ;
LARSSON, O ;
ASHCROFT, FM ;
RORSMAN, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1993, 472 :665-688
[3]   GLUCOSE INDUCES CLOSURE OF SINGLE POTASSIUM CHANNELS IN ISOLATED RAT PANCREATIC BETA-CELLS [J].
ASHCROFT, FM ;
HARRISON, DE ;
ASHCROFT, SJH .
NATURE, 1984, 312 (5993) :446-448
[4]   2 TYPES OF CA CHANNEL IN RAT PANCREATIC BETA-CELLS [J].
ASHCROFT, FM ;
KELLY, RP ;
SMITH, PA .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1990, 415 (04) :504-506
[5]  
ASHCROFT SJH, 1974, DIABETOLOGIA, V11, P279
[6]   Voltage dependent Na+ and Ca2+ currents in human pancreatic islet beta-cells: Evidence for roles in the generation of action potentials and insulin secretion [J].
Barnett, DW ;
Pressel, DM ;
Misler, S .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1995, 431 (02) :272-282
[7]  
BONDAR RJL, 1974, CLIN CHEM, V20, P586
[8]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[9]   INTRACELLULAR ATP DIRECTLY BLOCKS K+ CHANNELS IN PANCREATIC B-CELLS [J].
COOK, DL ;
HALES, CN .
NATURE, 1984, 311 (5983) :271-273
[10]   POTASSIUM AND RUBIDIUM PERMEABILITY AND POTASSIUM CONDUCTANCE OF THE BETA-CELL MEMBRANE IN MOUSE ISLETS OF LANGERHANS [J].
DAWSON, CM ;
CROGHAN, PC ;
SCOTT, AM ;
BANGHAM, JA .
QUARTERLY JOURNAL OF EXPERIMENTAL PHYSIOLOGY AND COGNATE MEDICAL SCIENCES, 1986, 71 (02) :205-222