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These data strongly support the proposed two-promoter system of the gene, with ubiquitous use of the distal promoter and additional use of the proximal promoter selectively in muscle. Interestingly, the mice were glucose intolerant and had somewhat elevated fasting and fed blood glucose levels; however, they did not have an abnormal insulin tolerance test, consistent with the less pronounced loss of phosphofructokinase-M in muscle. Isolated perifused islets showed about 50% decreased glucose-stimulated insulin secretion and reduced amplitude and regularity of secretory oscillations. Oscillations in cytoplasmic free Ca<jats:sup>2+<\/jats:sup>and the rise in the ATP\/ADP ratio appeared normal. Secretory oscillations still occurred in the presence of diazoxide and high KCl, indicating an oscillation mechanism not requiring dynamic Ca<jats:sup>2+<\/jats:sup>changes. The results suggest the importance of phosphofructokinase-M for insulin secretion, although glucokinase is the overall rate-limiting glucose sensor. Whether the Ca<jats:sup>2+<\/jats:sup>oscillations and residual insulin oscillations in this mouse model are due to the residual 2\u20135% phosphofructokinase-M or to other phosphofructokinase isoforms present in islets or involve another metabolic oscillator remains to be determined.<\/jats:p>","DOI":"10.1152\/ajpendo.00168.2007","type":"journal-article","created":{"date-parts":[[2007,6,27]],"date-time":"2007-06-27T00:29:35Z","timestamp":1182904175000},"page":"E794-E801","source":"Crossref","is-referenced-by-count":20,"title":["Tissue-dependent loss of phosphofructokinase-M in mice with interrupted activity of the distal promoter: impairment in insulin secretion"],"prefix":"10.1152","volume":"293","author":[{"given":"Ann-Marie T.","family":"Richard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic-Luc","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie 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