uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Tissue-dependent loss of phosphofructokinase-M in mice with interrupted activity of the distal promoter: impairment in insulin secretion
Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Show others and affiliations
2007 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 293, no 3, E794-801 p.Article in journal (Refereed) Published
Abstract [en]

Phosphofructokinase is a key enzyme of glycolysis that exists as homo- and heterotetramers of three subunit isoforms: muscle, liver, and C type. Mice with a disrupting tag inserted near the distal promoter of the phosphofructokinase-M gene showed tissue-dependent differences in loss of that isoform: 99% in brain and 95-98% in islets, but only 50-75% in skeletal muscle and little if any loss in heart. This correlated with the continued presence of proximal transcripts specifically in muscle tissues. 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(2+) 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(2+) changes. The results suggest the importance of phosphofructokinase-M for insulin secretion, although glucokinase is the overall rate-limiting glucose sensor. Whether the Ca(2+) oscillations and residual insulin oscillations in this mouse model are due to the residual 2-5% phosphofructokinase-M or to other phosphofructokinase isoforms present in islets or involve another metabolic oscillator remains to be determined.

Place, publisher, year, edition, pages
2007. Vol. 293, no 3, E794-801 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-162874DOI: 10.1152/ajpendo.00168.2007PubMedID: 17595219OAI: oai:DiVA.org:uu-162874DiVA: diva2:461781
Available from: 2011-12-05 Created: 2011-12-05 Last updated: 2011-12-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Webb, Dominic-Luc
In the same journal
American Journal of Physiology. Endocrinology and Metabolism
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 160 hits
ReferencesLink to record
Permanent link

Direct link