Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 31 P191 | DOI: 10.1530/endoabs.31.P191

SFEBES2013 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (67 abstracts)

Novel inositol pyrophosphate and insulin sensitivity in response to muscle contraction in glucose intolerant humans

Jane Naufahu 1 , Peter Watt 2 , Louise Mellish 3 , Bradley Elliott 1 , Anna Kerekgyarto 1 & Richard Mackenzie 1


1University of Westminster, London, UK; 2Brighton University, Brighton, UK; 3King’s College Hospital, London, UK.


Peripheral insulin resistance is a major defect associated with glucose intolerance and type two diabetes. Yet the mechanism(s) responsible for this defect remain to be determined. Inositol pyrophosphate (IP7) is formed via the enzyme IP6K1 from IP6. The inhibition of Akt, and the potential decrease in insulin signalling, through the binding of IP7 to the Akt PH domain represents an exciting research area.

Firstly, we will characterise this mechanism in humans for the first time. Secondly, we will test for correlations of IP6K1 activity with in vivo measures of insulin sensitivity (SI2*) and glucose effectiveness (SG2*). Thirdly, using a stimulus that is known to improve insulin sensitivity (i.e. muscle contraction), we will test if this pathway can be altered following exercise in glucose intolerant individuals (mean (S.D.) age 52.2 (5.3) years; BMI 30.7 (6.4); HOMA-IR 3.4 (1.2); fasting blood glucose 5.0 (0.5) mmol/l) (n=4). Analysis of our data is nearing completion but preliminary results show that area under the curve for glucose (AUCGlu) is lower immediately post high-intensity intermittent exercise (IE) (resting control; 1276 (60) vs IE; 1197 (115) mmol/l per min) while acute insulin response to glucose (AIRglu) is elevated following IE at 745 (98) compared to 391 (104) μU/ml per min for the control trial. These data suggest that this form of exercise improves glucose tolerance. We now wish to determine if these changes are reflected in activity levels and protein content of IP6K1 and IP6/IP7, respectively in our complete data set (n=15). These samples have been collected using standard muscle biopsy methodologies and will be fully analysed and presented in our final abstract.

Declaration of funding: Supported by The Society of Endocrinology and The University of Westminster.

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