Rats with non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal injection of streptozocin are known to have a deficient insulin response to glucose. To evaluate to what extent this glucose insensitivity can be attributed to a pertubation of the islet glucose metabolism, we estimated the rates of glucose phosphorylation, glucose utilization, oxygen consumption, and glucose oxidation in islets isolated from normal and NIDDM rats and compared these values with rates of islet insulin biosynthesis and release in vitro. The data confirm that islets from rats with NIDDM display a deficient response to glucose of both insulin biosynthesis and release that is still present after an overnight culture of the islets at 5.5 mM glucose. Furthermore, they show that islets of these rats have 1) normal low- and high-Km glucose-phosphorylating activities and no major alteration of the glucose utilization rate, 2) decreased insulin release in response to glyceraldehyde, 3) decreased rates of basal respiration and glucose oxidation and a markedly reduced stimulation by glucose of both islet oxygen consumption and glucose oxidation, and 4) decreased glucose-stimulated net 45Ca uptake. We conclude that the relative unresponsiveness to glucose of islets from NIDDM rats is associated with, and perhaps due to, a deficient islet glucose metabolism. This defect is not due to gross alterations in the glycolytic pathway but probably reflects alteration in the islet mitochondria function.
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Original Articles|
September 01 1988
Insulin Production and Glucose Metabolism in Isolated Pancreatic Islets of Rats With NIDDM
Bernard Portha;
Bernard Portha
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Marie-Hélène Giroix;
Marie-Hélène Giroix
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Patricia Serradas;
Patricia Serradas
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Nils Welsh;
Nils Welsh
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Claes Hellerström;
Claes Hellerström
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Abdullah Sener;
Abdullah Sener
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Willy J Malaisse
Willy J Malaisse
Laboratoire de Physiologie du Développement, Université Paris 7
Paris, France
Department of Medical Cell Biology, Uppsala University, Uppsala
Sweden
Laboratory of Experimental Medicine, Brussels Free University
Brussels, Belgium
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Address correspondence and reprint requests to Dr. Bernard Portha, Laboratoire de Physiologie du Développement, UA 307 (CNRS), Université Paris 7, Tour 54-2, Place Jussieu, F-75251 Paris Cédex 05, France.
Diabetes 1988;37(9):1226–1233
Article history
Received:
September 25 1987
Revision Received:
February 26 1988
Accepted:
February 26 1988
PubMed:
3044888
Citation
Bernard Portha, Marie-Hélène Giroix, Patricia Serradas, Nils Welsh, Claes Hellerström, Abdullah Sener, Willy J Malaisse; Insulin Production and Glucose Metabolism in Isolated Pancreatic Islets of Rats With NIDDM. Diabetes 1 September 1988; 37 (9): 1226–1233. https://doi.org/10.2337/diab.37.9.1226
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