Author(s): Knobler H, Weiss Y, Peled M, Groner Y
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Abstract 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 beta-cell PFK activity in glucose-induced insulin secretion.
This article was published in Diabetes
and referenced in Journal of Diabetes & Metabolism