High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals

Naufahu, J., Elliott, B., Markiv, A., Dunning-Foreman, P., McGrady, M., Howard, D., Watt, P.W. and Mackenzie, R.W.A. 2018. High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals. Journal of Clinical Endocrinology and Metabolism. 103 (4), pp. 1479-1490. doi:10.1210/jc.2017-02019

TitleHigh intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals
AuthorsNaufahu, J., Elliott, B., Markiv, A., Dunning-Foreman, P., McGrady, M., Howard, D., Watt, P.W. and Mackenzie, R.W.A.
Abstract

Context
Insulin resistance in skeletal muscle contributes to whole body hyperglycaemia and the secondary complications associated with type 2 diabetes. Inositol hexakisphosphate kinase-1 (IP6K1) may inhibit insulin-stimulated glucose transport in this tissue type.

Objective
Muscle and plasma IP6K1 were correlated with two-compartment models of glucose control in insulin-resistant hyperinsulimic individuals. Muscle IP6K1 was also compared following two different exercise trials.

Methods
Nine pre-diabetic [HbA1c; 6.1 (0.2) %)] were recruited to take part in a resting control, a continuous exercise (90% of lactate threshold) and a high-intensity exercise trial (6 x 30 sec sprints). Muscle biopsies were drawn pre- and post each 60-minute trial. A labeled ([6,62H2]glucose) intravenous glucose tolerance test (IVGTT) was performed immediately after the second muscle sample.

Results
Fasting muscle IP6K1 content did not correlate with SI2* (P = 0.961). High-intensity exercise reduced IP6K1 muscle protein and mRNA expression (P = 0.001). There was no effect on protein IP6K1 content following continuous exercise. Akt308 phosphorylation of was significantly greater following high-intensity exercise. Intermittent exercise reduced hepatic glucose production (HGP) following the same trial. The same intervention also improved SI2* and this was significantly greater compared to the continuous exercise improvements. Our in vitro experiment demonstrated that the chemical inhibition of IP6K1 increased insulin signaling in C2C12 myotubes.

Conclusions
The in vivo and in vitro approaches used in the current study suggest that a decrease in muscle IP6K1 may be linked to whole body improvements in SI2*. In addition, high-intensity exercise reduces HPG in insulin-resistant individuals.

JournalJournal of Clinical Endocrinology and Metabolism
Journal citation103 (4), pp. 1479-1490
ISSN0021-972X
Year2018
PublisherOxford University Press
Accepted author manuscriptNaufahu 2017.pdf
Digital Object Identifier (DOI)doi:10.1210/jc.2017-02019
Web address (URL)https://academic.oup.com/jcem/advance-article/doi/10.1210/jc.2017-02019/4781494#.Wk1mGUDPy4U.twitter
Publication dates
Published in printApr 2018
Published online29 Dec 2017
Published29 Dec 2017

Related outputs

Effects of upper-body, lower-body, or combined resistance training on the ratio of follistatin and myostatin in middle-aged men
Bagheri, R., Rashidlamir, A., Motevalli, M., Elliott, B., Mehrabani, J. and Wong, A. 2019. Effects of upper-body, lower-body, or combined resistance training on the ratio of follistatin and myostatin in middle-aged men. European Journal of Applied Physiology. 119 (9), p. 1921–1931. doi:10.1007/s00421-019-04180-z

Short-Term Exercise Training Inconsistently Influences Basel Testosterone in Older Men: A Systematic Review and Meta-Analysis
Hayes, L. and Elliott, B. 2019. Short-Term Exercise Training Inconsistently Influences Basel Testosterone in Older Men: A Systematic Review and Meta-Analysis. Frontiers in Physiology. 9 (1878). doi:10.3389/fphys.2018.01878

Hydrophobically modified chitosan nanoliposomes for intestinal drug delivery
Zariwala, M., Bendre, H., Markiv, A., Farnaud, S., Renshaw, D., Taylor, K.M.G. and Somavarapu, S. 2018. Hydrophobically modified chitosan nanoliposomes for intestinal drug delivery. International Journal of Nanomedicine. 13 (5837), p. 5848. doi:10.2147/IJN.S166901

The Effect of Omega-3 Supplementation on Exercise-Induced Muscle Damage
Kyriakidou, Y., Wood, C., Elliott, B. and Dolci, A. 2018. The Effect of Omega-3 Supplementation on Exercise-Induced Muscle Damage. Europhysiology 2018. London 14 - 16 Sep 2018 The Physiological Society.

Activin subfamily peptides predict chronological age in humans
Barrios-Silva, L., Parnell, M., Shinwari, Z., Chaudhary, G., Xenofontos, T, van Bekhoven, A., McArthur, S. and Elliott, B. 2018. Activin subfamily peptides predict chronological age in humans. Physiological Report. 6 (17), p. e13823. doi:10.14814/phy2.13823

Glycosylation and Disease
Dwek, M. and Markiv, A. 2018. Glycosylation and Disease. eLS. doi:10.1002/9780470015902.a0002151.pub3

Differing Effects of Younger and Older Human Plasma on C2C12 Myocytes in Vitro
Kalampouka, I., van Bekhoven, A. and Elliott, B. 2018. Differing Effects of Younger and Older Human Plasma on C2C12 Myocytes in Vitro. Frontiers in Physiology. 9 (152), pp. 1-7. doi:10.3389/fphys.2018.00152

PhytoCloud: A gamified Mobile Web Application to modulate diet and physical activity of women with breast cancer
Economou, D., Dwek, M., Elliott, B., Ramezanian Kalahroudi, M. and Azimi, T. 2017. PhytoCloud: A gamified Mobile Web Application to modulate diet and physical activity of women with breast cancer. IEEE 30th International Symposium on Computer-Based Medical Systems. Thessaloniki, Greece 22 Jun - 24 Sep 2017 IEEE . doi:10.1109/CBMS.2017.164

Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation
Elliott, B., Herbert, P., Sculthorpe, N., Grace, F., Stratton, D. and Hayes, L. 2017. Lifelong exercise, but not short-term high-intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation. Physiological Report. 5 (13), p. e13343. doi:10.14814/phy2.13343

Melanin-concentrating hormone in peripheral circulation in the human
Naufahu, J., Alzaid, F., Fiuza Brito, M., Doslikova, B., Valencia, T. and Murray, J.F. 2017. Melanin-concentrating hormone in peripheral circulation in the human. Journal of Endocrinology. 232, pp. 513-523. doi:10.1530/JOE-16-0240

A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition-Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India
Kapoor, N., Naufahu, J., Tewfik, S., Bhatnagar, S., Garg, R. and Tewfik, I. 2017. A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition-Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India. Integrative Cancer Therapies. 6 (1), pp. 74-84. doi:10.1177/1534735416651968

Circulating myostatin is reduced with aging in humans but not altered by short-term, high intensity training
Elliott, B., Shinwari, Z.B., Altayar, Z., Barrios, L., Chaudhary, G.A., Hanifa, E., Parnell, M., Xenofontos, T., Sculthorpe, N., Herbert, P., Grace, F. and Hayes, L. 2016. Circulating myostatin is reduced with aging in humans but not altered by short-term, high intensity training. Physiology 2016. Dublin, Ireland 29 2016 - 31 Jul 2017 The Physiological Society.

Complete and Voluntary Starvation of 50 days
Elliott, B., Mina, A. and Ferrier, C. 2016. Complete and Voluntary Starvation of 50 days. Clinical Medical Insights: Case Reports. 2016:9, pp. 67-70. doi:10.4137/CCRep.S39776

The role of acute ambient hypoxia in the regulation of myostatin
Elliott, B. 2015. The role of acute ambient hypoxia in the regulation of myostatin. PhD thesis University of Westminster Biomedical Sciences

Wearable technology in academia: the use of Google Glass in the life sciences
Elliott, B. and Sukan, A. 2015. Wearable technology in academia: the use of Google Glass in the life sciences. Compass: Journal of Learning & Teaching . 6 (10).

Acute hypoxia reduces plasma myostatin independent of hypoxic dose
Elliott, B., Simonson, T.S., Getting, S.J., Renshaw, D., Wagner Peter, D. and MacKenzie, R. 2015. Acute hypoxia reduces plasma myostatin independent of hypoxic dose. 8th International Conference on Cachexia, Sarcopenia and Muscle Wasting. Paris 04 - 06 Dec 2015 The Society on Sarcopenia, Cachexia and Wasting Disorders.

Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes
MacKenzie, R. and Elliott, B. 2014. Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 7, pp. 55-67. doi:10.2147/DMSO.S48260

Fabrication and characterization of novel hydrophobically modified chitosan nanoliposomes for oral iron delivery
Zariwala, M., Bendre, H., Markiv, A., Farnaud, S., Somavarapu, S. and Renshaw, D. 2014. Fabrication and characterization of novel hydrophobically modified chitosan nanoliposomes for oral iron delivery. European Iron Club Annual Meeting 2014. Verona, Italy 11 - 14 Sep 2014

What range of methods is available to evaluate the implementation and impact of complex environmental policies on complex systems?
Fagan-Watson, B., Watson, T., Elliott, B., Vanner, R., Shaw, Ben and Morris, S. 2014. What range of methods is available to evaluate the implementation and impact of complex environmental policies on complex systems? A report to the Department for Environment, Food and Rural Affairs. Policy Studies Institute. Defra, London.

Acute hypoxia alters myotube size in vitro and myostatin signalling in vivo
Elliott, B., Renshaw, D., Getting, S.J., Watt, P.W. and MacKenzie, R. 2014. Acute hypoxia alters myotube size in vitro and myostatin signalling in vivo. FASEB. San Diego Jul 2015 Federation of American Societies for Experimental Biology.

The role of acute hypoxia in skeletal muscle atrophy
Elliott, B., Renshaw, D., Getting, S.J., Watt, P., Howard, D. and MacKenzie, R. 2014. The role of acute hypoxia in skeletal muscle atrophy. Physiology. London 30 Jun 2014 The Physiological Society.

Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes
Mackenzie, R.W.A. and Elliott, B.T. 2014. Akt/PKB activation and insulin signaling: a novel insulin signaling pathway in the treatment of type 2 diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 7, pp. 55-64. doi:10.2147/DMSO.S48260

The roles of melanin-concentrating hormone in energy balance and reproductive function: are they connected?
Naufahu, J., Cunliffe, A. and Murray, J.F. 2013. The roles of melanin-concentrating hormone in energy balance and reproductive function: are they connected? Reproduction. 146, pp. R141-R150. doi:10.1530/REP-12-0385

The effects of consuming a medium-high protein diet on weight loss, body composition and satiety
Hutson, R. and Naufahu, J. 2013. The effects of consuming a medium-high protein diet on weight loss, body composition and satiety. International Journal of Food, Nutrition and Public Health. 6 (2), pp. 105-121.

Attenuation of plasma annexin A1 in human obesity
Kosicka, A., Cunliffe, A., Mackenzie, R.W.A., Gulrez Zariwala, M., Perretti, M., Flower, R.J. and Renshaw, D. 2013. Attenuation of plasma annexin A1 in human obesity. FASEB Journal. 27 (1), pp. 368-378. doi:10.1096/fj.12-213728

Partial heat acclimation of athletes with spinal cord lesion
Castle, P.C., Pasan Kularatne, B., Brewer, J., Mauger, A.R., Austen, R.A., Tuttle, J.A., Sculthorpe, N., Mackenzie, R.W.A., Maxwell, N.S. and Webborn, A.D.J. 2013. Partial heat acclimation of athletes with spinal cord lesion. European Journal of Applied Physiology. 113 (1), pp. 109-115. doi:10.1007/s00421-012-2417-6

Concurrent resistance and aerobic exercise stimulates both myofibrillar and mitochondrial protein synthesis in sedentary middle-aged men
Donges, C.E., Burd, N.A., Duffield, R., Smith, G.C., West, D.D.W., Short, M.J., Mackenzie, R.W.A., Plank, L.D., Shepherd, P.R., Phillips, S.M. and Edge, J.A. 2012. Concurrent resistance and aerobic exercise stimulates both myofibrillar and mitochondrial protein synthesis in sedentary middle-aged men. Journal of Applied Physiology. 112 (12), pp. 1992-2001. doi:10.​1152/​japplphysiol.​00166.​2012

The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes
MacKenzie, R., Elliott, B., Maxwell, N.S., Brickley, G. and Watt, P.W. 2012. The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes. Journal of Clinical Endocrinology & Metabolism. 97 (1), pp. 155-62. doi:10.1210/jc.2011-1843

Intermittent Exercise with and without Hypoxia Improves Insulin Sensitivity in Individuals with Type 2 Diabetes
MacKenzie, R., Maxwell, N.S., Castle, P.C., Elliot, B., Brickley, G., Watt, P.W. and Elliott, B. 2012. Intermittent Exercise with and without Hypoxia Improves Insulin Sensitivity in Individuals with Type 2 Diabetes. Journal of Clinical Endocrinology & Metabolism. 97 (4), pp. 46-55. doi:10.1210/jc.2011-2829

The Central Role of Myostatin in Skeletal Muscle and Whole Body Homeostasis
Elliott, B., Renshaw, D., Getting, S.J. and MacKenzie, R. 2012. The Central Role of Myostatin in Skeletal Muscle and Whole Body Homeostasis. Acta Physiologica. 205 (3), pp. 324-40. doi:10.1111/j.1748-1716.2012.02423.x

Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes
Mackenzie, R.W.A., Maxwell, N.S., Castle, P.C., Elliott, B.T., Brickley, G. and Watt, P.W. 2012. Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism. 97 (4), pp. E546-E555. doi:10.1210/jc.2011-2829

The central role of myostatin in skeletal muscle and whole body homeostasis
Elliott, B.T., Renshaw, D., Getting, S.J. and Mackenzie, R.W.A. 2012. The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiologica. 205 (3), pp. 324-340. doi:10.1111/j.1748-1716.2012.02423.x

The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes
Mackenzie, R.W.A., Elliott, B.T., Maxwell, N.S., Brickley, G. and Watt, P.W. 2012. The effect of hypoxia and work intensity on insulin resistance in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism. 97 (1), pp. 155-162. doi:10.1210/jc.2011-1843

Heat acclimation improves intermittent sprinting in the heat but additional pre-cooling offers no further ergogenic effect
Castle, P.C., Mackenzie, R.W.A., Maxwell, N.S., Webborn, A.D.J. and Watt, P.W. 2011. Heat acclimation improves intermittent sprinting in the heat but additional pre-cooling offers no further ergogenic effect. Journal of Sports Sciences. 29 (11), pp. 1125-1134. doi:10.1080/02640414.2011.583673

Acute hypoxia and exercise improve insulin sensitivity (S(I) (2) *) in individuals with type 2 diabetes
Mackenzie, R.W.A., Maxwell, N.S., Castle, P.C., Brickley, G. and Watt, P.W. 2011. Acute hypoxia and exercise improve insulin sensitivity (S(I) (2) *) in individuals with type 2 diabetes. Diabetes - Metabolism: Research and Reviews. 27 (1), pp. 94-101. doi:10.1002/dmrr.1156

Circulating melanin concentrating hormone (MCH) concentrations in the menstrual cycle
Naufahu, J., Cunliffe, A. and Murray, J.F. 2010. Circulating melanin concentrating hormone (MCH) concentrations in the menstrual cycle. Society for Reproduction and Fertility. Sutton Bonnington 11th - 13th July 2010

Preliminary characterisation of the neuropeptide melanin concentrating hormone in humans
Naufahu, J. 2010. Preliminary characterisation of the neuropeptide melanin concentrating hormone in humans. PhD thesis University of Westminster School of Life Sciences

Acute hypoxia improves insulin sensitivity (SI2*) and β cell function in individuals with Type 2 Diabetes
Mackenzie, R.W.A., Elliott, B.T., Brickley, G. and Watt, P.W. 2010. Acute hypoxia improves insulin sensitivity (SI2*) and β cell function in individuals with Type 2 Diabetes. The Physiological Society. University of Manchester

Influence of hypohydration on intermittent sprint performance in the heat
Maxwell, N.S., Mackenzie, R.W.A. and Bishop, D. 2009. Influence of hypohydration on intermittent sprint performance in the heat. International Journal of Sports Physiology and Performance. 4 (1), pp. 54-67.

"I felt really inspired by it, it was really interesting to interact with the pupils": Active citizenship in the British undergraduate social science curriculum
Watt, P.W., Gifford, C., Koster, S. and Clark, W. 2009. "I felt really inspired by it, it was really interesting to interact with the pupils": Active citizenship in the British undergraduate social science curriculum. Greek Social Science Tribune - Special English Edition: From a National Identity to a European One. 14 (55), pp. 153-174.

Intermittent exercise decreases insulin resistance in the 48 hrs following exercise in individuals with type 2 diabetes
Mackenzie, R.W.A. and Watt, P.W. 2009. Intermittent exercise decreases insulin resistance in the 48 hrs following exercise in individuals with type 2 diabetes. Endocrine Society 91st Annual Meeting. Washington, DC 10 - 13 Jun 2009

Exercise and acute hypoxia improve insulin sensitivity (SI2*) in individuals with type 2 diabetes
Mackenzie, R.W.A. and Watt, P.W. 2009. Exercise and acute hypoxia improve insulin sensitivity (SI2*) in individuals with type 2 diabetes. Society for Endocrinology BES 2009. Harrogate 16 - 19 Mar 2009

Heat acclimation improves intermittent sprint performance in the heat, but additional pre-cooling is not further ergogenic
Castle, P.C., Mackenzie, R.W.A., Maxwell, N.S., Webborn, A.D.J. and Watt, P.W. 2009. Heat acclimation improves intermittent sprint performance in the heat, but additional pre-cooling is not further ergogenic. BASES Annual Conference. Leeds Metropolitan University 01 - 03 Sep 2009

Acute normobaric hypoxia stimulates erythropoietin release
Mackenzie, R.W.A., Watt, P.W. and Maxwell, N.S. 2008. Acute normobaric hypoxia stimulates erythropoietin release. High Altitude Medicine and Biology. 9 (1), pp. 28-37. doi:10.1089/ham.2007.1043

Voluntary resistance running wheel activity pattern and skeletal muscle growth in rats
Legerlotz, K., Elliott, B., Guillemin, B. and Smith, H. 2008. Voluntary resistance running wheel activity pattern and skeletal muscle growth in rats. Experimental Physiology. 93 (6), pp. 754-62. doi:10.1113/expphysiol.2007.041244

Acute hypoxia alters glucose tolerance in type 2 diabetes
Mackenzie, R.W.A., Hammond, E. and Watt, P.W. 2007. Acute hypoxia alters glucose tolerance in type 2 diabetes. The Endocrine Society 89th Annual Meeting. Toronto, Canada 02 - 05 Jun 2007

Increased carbon dioxide expiration in recovery from maximal exercise in children with cystic fibrosis
Brickley, G., Adams, A., Mackenzie, R.W.A., Lenton, J. and Seddon, P. 2006. Increased carbon dioxide expiration in recovery from maximal exercise in children with cystic fibrosis. American Thoracic Society International Conference. San Diego 19 - 24 May 2006

Physical activity and fitness in children with Cystic Fibrosis
Adams, A., Mackenzie, R.W.A., Lenton, J., Brickley, G. and Seddon, P. 2006. Physical activity and fitness in children with Cystic Fibrosis. Journal of Cystic Fibrosis. 5 (sup. 1), p. S80.

Physical activity and fitness in children with cystic fibrosis
Adams, A., Lenton, J., Brickley, G., Mackenzie, R.W.A. and Seddon, P. 2006. Physical activity and fitness in children with cystic fibrosis. 29th European Cystic Fibrosis Conference. Copenhagen, Denmark 15 - 18 Jun 2006

Invited Response – Levine, B D & Stray-Gundersen, J (2005). Comments on Point: Counterpoint "Positive effects of intermittent hypoxia (live high:train low) on exercise performance are/are not mediated primarily by augmented red cell volume"
Mackenzie, R.W.A. 2005. Invited Response – Levine, B D & Stray-Gundersen, J (2005). Comments on Point: Counterpoint "Positive effects of intermittent hypoxia (live high:train low) on exercise performance are/are not mediated primarily by augmented red cell volume". Journal of Applied Physiology. 99 (6), pp. 2453-2462. doi:10.1152/japplphysiol.01157.2005

Permalink - https://westminsterresearch.westminster.ac.uk/item/q3x34/high-intensity-exercise-decreases-ip6k1-muscle-content-improves-insulin-sensitivity-in-glucose-intolerant-individuals


Share this
Tweet
Email