Placeholder image for staff profiles

Professor A. Margot Umpleby


Diabetes & Metabolic Medicine Research
+44 (0)1483 688579
21 PG 00

Academic and research departments

School of Biosciences and Medicine.

Biography

Areas of specialism

Stable isotope techniques in the study of human metabolism

My qualifications

1976
BA Natural Sciences
Cambridge
1982
PhD Medicine
University of London

Affiliations and memberships

Department of Nutritional Sciences

Research

Research interests

My publications

Publications

V Hordern, J Wright, M Umpleby, L Jacobsen, D Russell-Jones (2001)Stable isotope studies show effect of insulin detemir and NPH on hepatic glucose output and peripheral glucose uptake after subcutaneous administration in healthy subjects, In: DIABETES50pp. A504-A505 AMER DIABETES ASSOC
M Umpleby, F Shojaee-Moradie, S Das, M Stolinski, W Jefferson, N Jackson, R Cramb, M Shahmanesh (2004)Adiponectin levels are reduced in HIV infection and after treatment and correlate with VLDL and IDL apolipoprotein B fractional catabolic rate, In: DIABETOLOGIA47pp. A233-A234
DL RussellJones, M Umpleby (1996)Protein anabolic action of insulin, growth hormone and insulin-like growth factor I, In: EUROPEAN JOURNAL OF ENDOCRINOLOGY135(6)pp. 631-642 SCANDINAVIAN UNIVERSITY PRESS
PV Carroll, M Umpleby, EL Alexander, VA Egel, KV Callison, PH Sonksen, DL Russell-Jones (1998)Recombinant human insulin-like growth factor-I (rhIGF-I) therapy in adults with type 1 diabetes mellitus: effects on IGFs, IGF-binding proteins, glucose levels and insulin treatment, In: CLINICAL ENDOCRINOLOGY49(6)pp. 739-746 BLACKWELL SCIENCE LTD
HB Holt, SH Wild, AD Postle, J Zhang, G Koster, M Umpleby, F Shojaee-Moradie, K Dewbury, PJ Wood, DI Phillips, CD Byrne (2007)Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men, In: DIABETOLOGIA50(5)pp. 1024-1032 SPRINGER
HB Holt, SH Wild, N Wareham, U Ekelund, M Umpleby, F Shojaee-Moradie, RIG Holt, DI Phillips, CD Byrne (2007)Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity, In: DIABETOLOGIA50(8)pp. 1698-1706 SPRINGER
RM Williams, R Amin, F Shojaee-Moradie, M Umpleby, KK Ong, CL Acerini, DB Dunger (2002)The effects of the specific growth hormone antagonist Pegvisomant on the GH/IGF-I axis and insulin sensitivity in adolescents with TIDM, In: DIABETES51pp. A117-A117 AMER DIABETES ASSOC
Simon Steenson, Margot Umpleby, JA Lovegrove, KG Jackson, Barbara Fielding (2017)Role of the enterocyte in fructose-induced hypertriglyceridaemia, In: Nutrients9(4)349 MDPI AG

Abstract: Dietary fructose has been linked to an increased post-prandial triglyceride (TG) level, which is an established independent risk factor for cardiovascular disease. Although much research has focused on the effects of fructose consumption on liver-derived very-low density lipoprotein (VLDL), emerging evidence also suggests that fructose may raise post-prandial TG levels by affecting the metabolism of enterocytes of the small intestine. Enterocytes have become well recognised for their ability to transiently store lipids following a meal and to thus control post-prandial TG levels according to the rate of chylomicron (CM) lipoprotein synthesis and secretion. The influence of fructose consumption on several aspects of enterocyte lipid metabolism are discussed, including de novo lipogenesis, apolipoprotein B48 and CM-TG production, based on the findings of animal and human isotopic tracer studies. Methodological issues affecting the interpretation of fructose studies conducted to date are highlighted, including the accurate separation of CM and VLDL. Although the available evidence to date is limited, disruption of enterocyte lipid metabolism may make a meaningful contribution to the hypertriglyceridaemia often associated with fructose consumption.

GF WATTS, MH CUMMINGS, M UMPLEBY, J QUINEY, R NAOUMOVA, GR THOMPSON, PH SONKSEN (1995)SIMVASTATIN DECREASES THE HEPATIC SECRETION OF VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN B-100 IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - PATHOPHYSIOLOGICAL AND THERAPEUTIC IMPLICATIONS, In: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION25(8)pp. 559-567 BLACKWELL SCIENCE LTD
R Williams, R Amin, F Shojaee-Moradie, M Umpleby, C Acerini, D Dunger (2003)Effects of the specific growth hormone receptor antagonist Pegvisomant on insulin sensitivity & lipid metabolism in adolescents with T1DM, In: DIABETES52pp. A334-A334
Margot Umpleby, F Shojaee-Moradie, Barbara Fielding, X Li, A Marino, N Alsini, Cheryl Isherwood, N Jackson, A Ahmad, M Stolinski, JA Lovegrove, Sigurd Johnsen, Agampodi Mendis, John Wright, ME Wilinska, R Hovorka, JD Bell, EL Thomas, GS Frost, Bruce Griffin (2017)Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets, In: Clinical Science131(21)pp. 2561-2573 Portland Press

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n=11) and low liver fat ‘controls’ (n= 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling. There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P

GF Watts, MH Cummings, M Umpleby, JR Quiney, R Naoumova, GR Thompsom, PH Sonksen (1995)Simvastatin decreases the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in heterozygous familial hypercholesterolaemia: Pathophysiological and therapeutic implications (vol 25, pg 559, 1995), In: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION25(12)pp. 980-980 BLACKWELL SCIENCE LTD
P Carroll, E Christ, I Gowrie, N Jackson, R Hovorka, E Albany, S Bowes, M Umpleby, P Sonksen, D RussellJones (1997)Daily rhIGF-I augments the anabolic effect of insulin in adults with IDDM., In: DIABETES46pp. 945-945 AMER DIABETES ASSOC
SB Bowes, M Umpleby, MH Cummings, NC Jackson, PV Carroll, C Lowy, PH Sonksen, DL RussellJones (1997)The effect of recombinant human growth hormone on glucose and leucine metabolism in Cushing's syndrome, In: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM82(1)pp. 243-246 ENDOCRINE SOC
M Shahmanesh, S Das, F Shojaee-Moradie, M Stolinski, W Jefferson, N Jackson, G Gilleran, NJ Crabtree, P Nightingale, R Cramb, M Umpleby (2004)The reduction in serum adiponectin levels in HIV patients correlates with apolipoprotein-B clearance, In: ANTIVIRAL THERAPY9(6)pp. L62-L63
I Sarac, K Backhouse, F Shojaee-Moradie, D Robertson, M Stolinski, M Umpleby (2009)The effect of rimonabant on resting energy expenditure, insulin sensitivity, plasma lipids and adipokines concentrations, In: BRITISH JOURNAL OF CLINICAL PHARMACOLOGY68(2)pp. 285-285
PV Carroll, M Umpleby, GS Ward, S Imuere, E Alexander, D Dunger, PH Sonksen, DL RussellJones (1997)rhIGF-I administration reduces insulin requirements, decreases growth hormone secretion, and improves the lipid profile in adults with IDDM, In: DIABETES46(9)pp. 1453-1458 AMER DIABETES ASSOC
M Stolinski, X Li, A Lo, F Shojaee-Moradie, S Alam, B Wheeler, C Pentecost, N Jackson, W Jefferson, M Umpleby (2006)A supervised exercise programme increases HDL ApoA-1 production rate in type 2 diabetes, In: DIABETOLOGIA49pp. 324-324
X Li, M Stolinski, N Jackson, M Umpleby (2009)Pre beta and alpha HDL kinetics measured by a stable isotopic and two step electrophoresis technique, In: DIABETOLOGIA52pp. S490-S490
X Li, M Stolinski, F Shojaee-Moradie, N Jackson, M Umpleby (2008)DEVELOPMENT OF A METHOD TO MEASURE HIGH DENSITY LIPOPROTEIN KINETICS USING STABLE ISOTOPES, In: ATHEROSCLEROSIS SUPP9(1)pp. 28-28
SE Joseph, N Heaton, D Potter, A Pernet, M Umpleby, SA Amiel (1998)Renal glucose production compensates for the liver during the anhepatic phase of liver transplantation., In: DIABETOLOGIA41pp. A68-A68 SPRINGER VERLAG
F Salomon, M Umpleby, RC Cuneo, PH Sonksen (1997)Protein, fat and glucose metabolism during treatment with recombinant human growth hormone in adults with growth hormone deficiency. Short-and long-term effects, In: ENDOCRINOLOGY AND METABOLISM4(2)pp. 121-128 BAILLIERE TINDALL
S Das, M Stolinski, W Jefferson, N Jackson, G Gilleran, M O'Connor, R Cramb, M Umpleby, M Shahmanesh (2003)Effects of HIV infection, antiviral treatment and body fat changes on V-LDL-apolipoprotein-B metabolism, In: ANTIVIRAL THERAPY8(4)pp. L6-L7
E Potocka, R Hovorka, R Baughman, M Umpleby, M Diaz, R Chen, J Cassidy, A Boss, P Richardson (2009)Technosphere insulin suppresses endogenous glucose production earlier than a rapid-acting analogue (lispro) and an inhaled insulin (Exubera (R)), In: DIABETOLOGIA52pp. S374-S374
S Das, M Stolinski, W Jefferson, N Jackson, G Gilleran, M O'Connor, R Cramb, M Shahmanesh, M Umpleby (2003)The relationship between fat distribution and VLDL and IDL metabolism in HIV-infected adults, In: ANTIVIRAL THERAPY8(4)pp. L52-L52
R Herring, F Shojaee-Moradie, M Umpleby, N Jackson, R Jones, D Derk-Jan, R Knight, D Russell-Jones (2014)Subcutaneous insulin detemir compared with NPH insulin increases brain potential responses with similar systemic metabolic effects in people with Type 1 diabetes, In: DIABETIC MEDICINE31pp. 62-62
F Shojaee-Moradie, K Backhouse, I Sarac, M Stoliniski, D Robertson, JD Bell, EL Thomas, D Russell-Jones, M Umpleby (2010)Fatty acid oxidation rate is higher in obese women than obese men, In: DIABETOLOGIA53
T Wolthers, DM Hoffman, AG Nugent, MW Duncan, M Umpleby, KKY Ho (2001)Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women, In: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM281(6)pp. E1191-E1196 AMER PHYSIOLOGICAL SOC

We have determined whether oral estrogen reduces the biological effects of growth hormone (GH) in GH-deficient (GHD) women compared with transdermal estrogen treatment. In two separate studies, eight GHD women randomly received either oral or transdermal estrogen for 8 wk before crossing over to the alternate route of administration. The first study assessed the effects of incremental doses of GH (0.5, 1.0, 2.0 IU/day for 1 wk each) on insulin-like growth factor I (IGF-I) levels during each estrogen treatment phase. The second study assessed the effects of GH (2 IU/day) on lipid oxidation and on protein metabolism using the whole body leucine turnover technique. Mean IGF-I level was significantly lower during oral estrogen treatment (P < 0.05) and rose dose dependently during GH administration by a lesser magnitude (P < 0.05) compared with transdermal treatment. Postprandial lipid oxidation was significantly lower with oral estrogen treatment, both before (P < 0.05) and during (P < 0.05) GH administration, compared with transdermal treatment. Protein synthesis was lower during oral estrogen both before and during GH administration (P < 0.05). Oral estrogen antagonizes several of the metabolic actions of GH. It may aggravate body composition abnormalities already present in GHD women and attenuate the beneficial effects of GH therapy. Estrogen replacement in GHD women should be administered by a nonoral route.

V Birzniece, UJ Meinhardt, MA Umpleby, DJ Handelsman, KKY Ho (2011)Interaction between testosterone and growth hormone on whole-body protein anabolism occurs in the liver, In: Journal of Clinical Endocrinology and Metabolism96(4)pp. 1060-1067
M Umpleby, F Shojaee-Moradie, B Fielding, X Li, C Isherwood, N Jackson, G Wilinska, R Hovorka, J Bell, EL Thomas, J Wright, GS Frost, B Griffin (2015)A DIET LOW IN SUGAR REDUCES THE PRODUCTION OF ATHEROGENIC LIPOPROTEINS IN MEN WITH HIGH LIVER FAT, In: ATHEROSCLEROSIS241(1)pp. E46-E46
MH CUMMINGS, GF WATTS, C PAL, M UMPLEBY, TR HENNESSY, R NAOUMOVA, PH SONKSEN (1995)INCREASED HEPATIC SECRETION OF VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN B-100 IN OBESITY - A STABLE-ISOTOPE STUDY, In: CLINICAL SCIENCE88(2)pp. 225-233 PORTLAND PRESS
D Elleri, JM Allen, M Biagioni, K Kumareswaran, L Leelarathna, K Caldwell, M Nodale, ME Wilinska, A Haidar, P Calhoun, C Kollman, MA Umpleby, CL Acerini, DB Dunger, R Hovorka (2012)Efficacy and safety of reduced prandial boluses during closed-loop insulin delivery in adolescents with type 1 diabetes, In: DIABETOLOGIA55pp. S86-S87 SPRINGER
MG Giannoulis, PH Sonksen, M Umpleby, L Breen, C Pentecost, M Whyte, CV McMillan, C Bradley, FC Martin (2006)The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial, In: The Journal of Clinical Endocrinology & Metabolism91(2)pp. 477-484

CONTEXT: Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men. OBJECTIVE: To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men. DESIGN, SETTINGS, AND PARTICIPANTS: A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65-80 yr). INTERVENTIONS: Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches. RESULTS: Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects. CONCLUSION: Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.

C Sibbons, L Boyle, GC Burdge, M Umpleby, KA Lilycrop, CA Hartwick, S Lanham-New, K Hart, BA Fielding (2015)Evaluation of fatty acid status in children of different nationalities, In: PROCEEDINGS OF THE NUTRITION SOCIETY74(OCE1)pp. E94-E94 CAMBRIDGE UNIV PRESS
Martin B. Whyte, Fariba Shojaee-Moradie, Sharaf E. Sharaf, Daniel J. Cuthbertson, Graham J. Kemp, Mark Barrett, Nicola C. Jackson, Roselle A. Herring, John Wright, E. Louise Thomas, Jimmy Bell, A. Margot Umpleby (2020)HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease, In: American Journal of Physiology-Endocrinology and Metabolism318(6)pp. E839-E847 American Physiological Society

Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8–32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P ˂ 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6–36.1% to 8.9% (4.4–17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.

R Sharma, S Tigas, M Rauchhaus, PP Poole-Wilson, AJ Coats, M Umpleby, PV Carroll, SD Anker (2005)Substrate metabolism in patients with chronic heart failure with and without cachexia, In: CIRCULATION112(17)pp. U660-U660
L Bhatia, E Scorletti, F Shojaee-Moradie, M Umpleby, A Fletcher, A Bateman, NP Curzen, GF Clough, P Calder, CD Byrne (2013)Peripheral and hepatic insulin resistance are key determinants of progression of non-alcoholic fatty liver disease severity independent of body fat percentage, In: DIABETIC MEDICINE30pp. 60-60 WILEY-BLACKWELL
CDT Byrne, HB Holt, SH Wild, N Wareham, U Ekelund, M Umpleby, E Shojaee-Moradie, RIG Holt, DI Phillips (2007)Differential impact of fatness, fitness and physical activity energy expenditure on whole body, liver and fat insulin sensitivity, In: DIABETOLOGIA50pp. S255-S255
MH CUMMINGS, GF WATTS, M UMPLEBY, TR HENNESSY, J QUINEY, PH SONKSEN (1995)INCREASED HEPATIC SECRETION OF VERY-LOW-DENSITY-LIPOPROTEIN APOLIPOPROTEIN B-100 IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - A STABLE-ISOTOPE STUDY, In: ATHEROSCLEROSIS113(1)pp. 79-89 ELSEVIER SCI PUBL IRELAND LTD
DJ Cuthbertson, MO Weickert, D Lythgoe, VS Sprung, R Dobson, F Shoajee-Moradie, M Umpleby, AFH Pfeiffer, EL Thomas, JD Bell, H Jones, GJ Kemp (2014)External validation of the fatty liver index and lipid accumulation product indices, using H-1-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals, In: EUROPEAN JOURNAL OF ENDOCRINOLOGY171(5)pp. 561-569 BIOSCIENTIFICA LTD
Barbara A Fielding, Bruce A Griffin, Wendy Hall, Leanne Hodson, Rona Antoni, A. Margot Umpleby, Tracey Robertson, Tom Preston, Matthew Brook, Katherine Pinnick (2020)Report of a member-led meeting: how stable isotope techniques can enhance human nutrition research, In: Proceedings of the Nutrition Society79(3)pp. 373-379 Cambridge University Press

A Nutrition Society member-led meeting was held on 9 January 2020 at The University of Surrey, UK. Sixty people registered for the event, and all were invited to participate, either through chairing a session, presenting a ‘3 min lightning talk’ or by presenting a poster. The meeting consisted of an introduction to the topic by Dr Barbara Fielding, with presentations from eight invited speakers. There were also eight lightning talks and a poster session. The meeting aimed to highlight recent research that has used stable isotope tracer techniques to understand human metabolism. Such studies have irrefutably shaped our current understanding of metabolism and yet remain a mystery to many. The meeting aimed to de-mystify their use in nutrition research.

O Hakim, F Shojaee-Moradie, K Hart, J Berry, R Eastell, F Gossiel, R Hannon, M Umpleby, B Griffin, S Lanham-New (2011)Evidence of a link between poor bone health, low vitamin D status and CVD risk in caucasian and asian women, In: BONE48pp. S197-S198
PH SONKSEN, F SALOMON, R CUNEO, M UMPLEBY, S BOWES (1991)CARDIAC CACHEXIA, In: BRITISH MEDICAL JOURNAL302(6778)pp. 725-726 BRITISH MED JOURNAL PUBL GROUP
Martin B Whyte, Fariba Shojaee-Moradie, Sharaf E Sharaf, Nicola Jackson, Barbara Fielding, Roman Hovorka, Jeewaka Mendis, David Russell-Jones, A Margot Umpleby (2018)Lixisenatide reduces chylomicron triacylglycerol due to increased clearance, In: The Journal of Clinical Endocrinology & Metabolism104(2)pp. 359-368 Oxford University Press (OUP)

Context GLP-1 agonists control postprandial glucose and lipid excursion in type 2 diabetes; however the mechanism(s) are unclear. Objective To determine the mechanism(s) of postprandial lipid and glucose control with lixisenatide (GLP-1 analogue) in type 2 diabetes. Design Randomised, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, UK Patients Eight obese men with type 2 diabetes (57.3±1.9yrs; BMI 30.3±1.0kg/m2, HbA1C 66.5±2.6mmol/mol, [8.2±0.3%]). Interventions Two metabolic studies, four-weeks after lixisenatide or placebo; with cross-over and repetition of studies. Main outcome measures Study one: very-low density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with iv bolus of [2H5]glycerol in a 12h study, with hourly feeding. Oral [13C]triolein, in a single meal, labelled enterally-derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable iv [6,6-2H2]glucose infusion. Results Study one: CM-TAG (but not VLDL-TAG) pool-size, was lower with lixisenatide (P=0.046). Lixisenatide reduced CM [13C]oleate AUC60-480min concentration (P=0.048) and increased CM-TAG clearance; with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (P=0.0051, P˂0.05). Total glucose production rate (Ra) (P=0.015), Rameal (P=0.0098) and acetaminophen AUC0-360min (P=0.006) were lower with lixisenatide than placebo. Conclusions Lixisenatide reduced [13C]oleate concentration, derived from a single meal in CM-TAG, as well as glucose Rameal, through delayed gastric emptying. However day-long CM production, measured with repeated meal-feeding, was not reduced by lixisenatide and decreased CM-TAG concentration was due to increased CM-TAG clearance.

AH Sam, ML Sleeth, EL Thomas, NA Ismail, NM Daud, E Chambers, F Shojaee-Moradie, M Umpleby, AP Goldstone, CW Le Roux, P Bech, M Busbridge, R Laurie, DJ Cuthbertson, A Buckley, MA Ghatei, SR Bloom, GS Frost, JD Bell, KG Murphy (2015)Circulating Pancreatic Polypeptide Concentrations Predict Visceral and Liver Fat Content, In: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM100(3)pp. 1048-1052 ENDOCRINE SOC
D RUSSELLJONES, M UMPLEBY, T HENNESEY, SB BOWES, KD HOPKINS, NC JACKSON, J KELLY, MJ THOMASON, F SHOJAEEMORADIE, RH JONES, PH SONKSEN (1993)INTRAVENOUS INSULIN-LIKE GROWTH FACTOR-I (IGF-I) UNLIKE INSULIN INCREASES WHOLE-BODY PROTEIN-SYNTHESIS IN NORMAL VOLUNTEERS, In: DIABETES42pp. A37-A37 AMER DIABETES ASSOC
S Zachariah, B Sheldon, E Shojaee-Moradie, N Jackson, K Backhouse, S Johnsen, M Umpleby, D Russell-Jones (2010)Mechanism for the differential effect of the long-acting insulin analog detemir on weight in patients with type 1 diabetes, In: DIABETOLOGIA53
Simon Steenson, Fariba Shojaee-Moradie, Martin Whyte, Kim G. Jackson, Julie A. Lovegrove, Barbara Fielding, Margot Umpleby (2020)The effect of fructose feeding on intestinal triacylglycerol production and de novo fatty acid synthesis in humans, In: Nutrients MDPI

A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (

R Dobson, MI Burgess, VS Sprung, A Irwin, M Hamer, J Jones, C Daousi, V Adams, GJ Kemp, F Shojaee-Moradie, M Umpleby, DJ Cuthbertson (2016)Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity, In: INTERNATIONAL JOURNAL OF OBESITY40(1)pp. 153-161 NATURE PUBLISHING GROUP
A Ahmad, C Isherwood, BA Fielding, JD Bell, EL Thomas, G Frost, F Shojaee-Moradie, M Umpleby, BA Griffin (2012)Individuals with moderately raised liver fat show a greater increase in liver fat in response to a high sugar diet, In: PROCEEDINGS OF THE NUTRITION SOCIETY71(OCE2)pp. E31-E31 CAMBRIDGE UNIV PRESS
F Shojaee-Moradie, DJ Cuthbertson, M Barrett, NC Jackson, R Herring, EL Thomas, J Bell, GJ Kemp, J Wright, M Umpleby (2016)Exercise training reduces liver fat and increases rates of VLDL clearance, but not VLDL production in NAFLD, In: Journal of Clinical Endocrinology and Metabolism101(11) Oxford University Press (OUP)

Context Randomised controlled trials in non-alcoholic fatty liver disease (NAFLD) have shown that regular exercise, even without calorie restriction, reduces liver steatosis. A previous study has shown that 16 weeks supervised exercise training in NAFLD did not affect total VLDL kinetics. Objective To determine the effect of exercise training on intrahepatocellular fat (IHCL) and the kinetics of large triglyceride-(TG)-rich VLDL1 and smaller denser VLDL2 which has a lower TG content. Design A 16 week randomised controlled trial. Patients 27 sedentary patients with NAFLD. Intervention Supervised exercise with moderate-intensity aerobic exercise or conventional lifestyle advice (control). Main outcome Very low density lipoprotein1 (VLDL1) and VLDL2-TG and apolipoproteinB (apoB) kinetics investigated using stable isotopes before and after the intervention. Results In the exercise group VO2max increased by 31±6% (mean±SEM) and IHCL decreased from 19.6% (14.8, 30.0) to 8.9% (5.4, 17.3) (median (IQR)) with no significant change in VO2max or IHCL in the control group (change between groups p

LS Bhatia, E Scorletti, F Shojaee-Moradie, M Umpleby, GF Clough, NP Curzen, PC Calder, CD Byrne (2014)High-dose n-3 fatty acid treatment in non-alcoholic fatty liver disease is independently associated with reduced hepatic steatosis and improved hepatic insulin sensitivity, In: DIABETIC MEDICINE31pp. 53-53
E Potocka, R Hovorka, RA Baughman, M Umpleby, MLM Diaz, R Chen, AH Boss, PC Richardson (2009)AFRESA (TM) Suppresses Endogenous Glucose Production Earlier Than a Rapid-Acting Analog (Lispro) and Inhaled Exubera (R), In: DIABETES58pp. A61-A61
A Ahmad, C Isherwood, JD Bell, EL Thomas, G Frost, M Umpleby, BA Griffin (2011)Impact of liver fat on the response of plasma triacylglycerol to diets high and low in extrinsic sugars, In: PROCEEDINGS OF THE NUTRITION SOCIETY70(OCE6)pp. E364-E364 CAMBRIDGE UNIV PRESS
X Li, M Stolinski, NC Jackson, MA Umpleby (2010)A NOVEL METHOD FOR THE MEASUREMENT OF PRE beta HDL AND alpha HDL KINETICS WITH STABLE ISOTOPIC LABELLING TECHNIQUES, In: ATHEROSCLEROSIS SUPPLEMENTS11(2)pp. 7-7
M Whyte, N Jackson, F Shojaee-moradie, R Beale, D Treacher, P Carroll, RH Jones, M Umpleby (2004)The effect of insulin therapy on glucose production rate, glucose uptake, lipolysis and proteolysis in non-surgical ICU patients, In: Diabetologia - Volume 47, Issue 1 Supplement, August 2004 - Proceedings of the 40th EASD Annual Meeting of the European Association for the Study of Diabetes47(Issue)pp. A216-A216

Background and aims: Recent data suggest that the use of insulin to maintain intensive glycaemic control amongst surgical ICU patients can improve morbidity and mortality. The value of this procedure in non-surgical patients is not known. Current insulin therapy for non-surgical patients in many ICUs aims to keep plasma glucose below 9 mmolll. The effect of this insulin therapy protocol on the catabolic response of critical illness, characterised by increased glucose production, increased lipolysis and proteolysis is unknown. Materials and methods: A prospective study was conducted in seven critically ill non-surgical patients (6M:1F, age 64±2.72 years; BMI 24.77 ± 0.77 kg/m2) within 36 hours of their admission to the ICU. Patients with diabetes mellitus, pancreatitis, oral steroid use within 1 month of entering the ICU, or liver disease (LFTs > twice normal range), were excluded. All patients were receiving 20% dextrose intravenously to provide 25kcal.kg-lday-l. Insulin was infused at a variable rate to maintain plasma glucose below 9 mmollL. Glucose production rate (Ra) and rate of uptake (Rd), glycerol Ra (a measure oflipolysis) and leucine Ra (a measure of proteolysis) were measured with a 3 hour primed infusion of [6,6- 2H2]glucose (l70mg, 1.7mg.min-I), [2H5]glycerol (0.15mg/kg, 0.61mg· kg-lhc1) and [l-l3C]leucine (1 mg/kg, 1 mg.kg-lhcl). Steady state sampling was performed at 150 to 180 minutes. Results are compared with fasting values from an age and weight matched healthy control group. All data presented are mean ± SEM. Results: The mean APACHE II score on the day of study was 15.43 ± 1.87. Mean plasma glucose at steady state was 7.95±0.73mmol· L-l. The mean glucose infusion rate was 22.83 ± 0.74 f.lmol.kg-lmin-l. The average insulin infusion rate was 4.31 ±0.73 U.hr-l which achieved plasma insulin concentrations of 655.21 ± 181.38 pmol.L-I. Endogenous glucose Ra was decreased (2.24±3.02f.lmol.kg-lmin-l, p

Roselle A. Herring, Fariba Shojaee-Moradie, Robert Garesse, Mary Stevenage, Nicola Jackson, Barbara Fielding, Agampodi Mendis, Sigurd Johnsen, Margot Umpleby, Melanie Davies, David L. Russell-Jones (2020)Full Title Metabolic effects of an SGLT2 inhibitor (dapagliflozin) during a period of acute insulin withdrawal and development of ketoacidosis in people with type 1 diabetes., In: Diabetes Care American Diabetes Association

Objective: To determine the effect of SGLT2 inhibitor dapagliflozin on glucose flux, lipolysis and ketone body concentrations during insulin withdrawal in people with type 1 diabetes. Research Design and Methods: A double-blind placebo controlled crossover study with a 4-week wash out period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days. Stable isotopes were infused to measure the rate of glucose production (Ra), disappearance (Rd) and lipolysis. At isotopic steady state insulin was withdrawn and the study terminated after 600 minutes or earlier if blood glucose reached 18mmol/L, bicarbonate 27 and

M Shahmanesh, S Das, M Umpleby (2009)Pre-treatment alterations in lipoprotein metabolism predict changes in blood lipids after antiretroviral therapy, In: ANTIVIRAL THERAPY14(7)pp. A56-A56
V Birzniece, MA Umpleby, A Poljak, DJ Handelsman, KK Ho (2013)Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy., In: Eur J Endocrinol169(3)pp. 321-327

OBJECTIVE: In hypopituitary men, oral delivery of unesterified testosterone in doses that result in a solely hepatic androgen effect enhances protein anabolism during GH treatment. In this study, we aimed to determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women. DESIGN: Eight healthy postmenopausal women received 2-week treatment with oral testosterone at a dose of 40 mg/day (crystalline testosterone USP). This dose increases portal concentrations of testosterone, exerting androgenic effects on the liver without a spillover into the systemic circulation. OUTCOME MEASURES: The outcome measures were whole-body leucine turnover, from which leucine rate of appearance (LRa, an index of protein breakdown) and leucine oxidation (Lox, a measure of irreversible protein loss) were estimated, energy expenditure and substrate utilization. We measured the concentration of liver transaminases as well as of testosterone, SHBG and IGF1. RESULTS: Testosterone treatment significantly reduced LRa by 7.1 ± 2.5% and Lox by 14.6 ± 4.5% (P