The selective impairment of glucose-induced insulin secretion in NIDDM can be attributed to defects in the glucose-signaling system. An alteration in the activity of phosphofructokinase (PFK), a key enzyme in the glycolytic pathway, may play a role in the abnormal glucose-induced insulin secretion. In this study, we evaluated insulin secretion in transgenic (Tg) mice overexpressing the liver-type subunit of phosphofructokinase (PFKL). Three independently derived Tg-PFKL lines showed random and postprandial hyperglycemia with diminished acute insulin response following intravenous glucose tolerance load. Isolated islets of Tg-PFKL mice exhibited a shift to the right of the glucose insulin dose curve. However, the maximal insulin secretory capacity, as well as the potentiation effect by arginine, were retained. PFK activity in Tg-PFKL islets was increased by 30–70%, because of the overexpression of PFKL. Conceivably, a selective overexpression of the PFKL isoform in Tg-PFKL mice altered the enzymatic properties of the tetrameric PFK and thereby affected glucose metabolism. A similar phenomenon was previously observed in transfected PC12-PFKL cells. The data show that overexpression of PFKL in transgenic mice was associated with diminished glucose-induced insulin response and suggest a mechanism to explain the role of β-cell PFK activity in glucose-induced insulin secretion.
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Original Articles|
September 01 1997
Impaired Glucose-Induced Insulin Response in Transgenic Mice Overexpressing the L-phosphofructokinase Gene
Hilla Knobler;
Hilla Knobler
Division of Endocrinology, Kaplan Hospital
Rehovot, Israel
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Yael Weiss;
Yael Weiss
Department of Molecular Genetics, The Weiz-mann Institute of Science
Rehovot
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Mira Peled;
Mira Peled
Department of Molecular Genetics, The Weiz-mann Institute of Science
Rehovot
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Yoram Groner
Yoram Groner
Department of Molecular Genetics, The Weiz-mann Institute of Science
Rehovot
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Address correspondence and reprint requests to Dr. Hilla Knobler, Division of Endocrinology, Kaplan Hospital Rehovot, or Dr. Yoram Groner, Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. E-mail: [email protected]; [email protected].
Diabetes 1997;46(9):1414–1418
Article history
Received:
January 29 1997
Revision Received:
May 08 1997
Accepted:
May 08 1997
PubMed:
9287040
Citation
Hilla Knobler, Yael Weiss, Mira Peled, Yoram Groner; Impaired Glucose-Induced Insulin Response in Transgenic Mice Overexpressing the L-phosphofructokinase Gene. Diabetes 1 September 1997; 46 (9): 1414–1418. https://doi.org/10.2337/diab.46.9.1414
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