Extract from the Register of European Patents

About this file: EP2515920

EP2515920 - LOW-CALORIC HIGH-PROTEIN NUTRITIONAL COMPOSITION FOR THE STIMULATION OF MUSCLE PROTEIN SYNTHESIS [Right-click to bookmark this link]
StatusThe patent has been granted
Status updated on  16.12.2016
Database last updated on 09.12.2019
Most recent event   Tooltip21.06.2019Change - opposition data/opponents data or that of the opponents representativepublished on 24.07.2019  [2019/30]
Applicant(s)For all designated states
N.V. Nutricia
Eerste Stationsstraat 186
2712 HM Zoetermeer / NL
[2012/44]
Inventor(s)01 / LUIKING, Yvette Charlotte
Zilverschoon 33
NL-5803 MA Venray / NL
02 / VERLAAN, George
Elstar 76
NL-6708 LZ Wageningen / NL
03 / JOURDAN, Marion
Steenstraat 18
NL-6828 CK Arnhem / NL
 [2012/44]
Representative(s)V.O.
P.O. Box 87930
2508 DH Den Haag / NL
[N/P]
Former [2014/51]Jansen, Cornelis Marinus
V.O.
Johan de Wittlaan 7
2517 JR Den Haag / NL
Former [2012/44]Jansen, Cornelis Marinus
VEREENIGDE Johan de Wittlaan 7
2517 JR Den Haag / NL
Application number, filing date10807402.223.12.2010
WO2010NL50887
Priority number, dateWO2009NL5080624.12.2009         Original published format: PCT/NL2009/050806
[2012/44]
Filing languageEN
Procedural languageEN
PublicationType: A2  Application without search report
No.:WO2011078677
Date:30.06.2011
Language:EN
[2011/26]
Type: A2 Application without search report 
No.:EP2515920
Date:31.10.2012
Language:EN
The application has been published by WIPO in one of the EPO official languages on 30.06.2011
[2012/44]
Type: B1 Patent specification 
No.:EP2515920
Date:17.12.2014
Language:EN
[2014/51]
Search report(s)International search report - published on:EP09.09.2011
ClassificationInternational:A61K35/20
[2011/33]
Designated contracting statesAL,   AT,   BE,   BG,   CH,   CY,   CZ,   DE,   DK,   EE,   ES,   FI,   FR,   GB,   GR,   HR,   HU,   IE,   IS,   IT,   LI,   LT,   LU,   LV,   MC,   MK,   MT,   NL,   NO,   PL,   PT,   RO,   RS,   SE,   SI,   SK,   SM,   TR [2012/44]
Extension statesBANot yet paid
MENot yet paid
TitleGerman:KALORIENARMES ERNÄHRUNGSPRODUKT MIT HOHEM PROTEINANTEIL ZUR BEFÖRDERUNG DER MUSKULÄRES PROTEINSYNTHESE[2014/16]
English:LOW-CALORIC HIGH-PROTEIN NUTRITIONAL COMPOSITION FOR THE STIMULATION OF MUSCLE PROTEIN SYNTHESIS[2012/44]
French:PRODUIT NUTRITIF HYPOCALORIQUE AVEC HAUT CONTENU EN PROTÉINES POUR LA STIMULATION DE LA SYNTHÈSE DES PROTÉINES MUSCULAIRES[2014/16]
Former [2012/44]KALORIENARME PROTEINREICHE ERNÄHRUNGSZUSAMMENSETZUNG ZUR STIMULATION DER MUSKELPROTEINSYNTHESE
Former [2012/44]PRODUIT NUTRITIF HYPOCALORIQUE AVEC HAUT CONTENU EN PROTEINES POUR LA STIMULATION DE LA SYNTHESE DES PROTEINES MUSCULAIRES
Entry into regional phase23.07.2012National basic fee paid 
23.07.2012Designation fee(s) paid 
23.07.2012Examination fee paid 
Examination procedure24.10.2011Request for preliminary examination filed
International Preliminary Examining Authority: EP
23.07.2012Examination requested  [2012/44]
25.11.2013Amendment by applicant (claims and/or description)
19.12.2013Despatch of a communication from the examining division (Time limit: M04)
07.02.2014Reply to a communication from the examining division
08.07.2014Communication of intention to grant the patent
03.11.2014Fee for grant paid
03.11.2014Fee for publishing/printing paid
03.11.2014Receipt of the translation of the claim(s)
Divisional application(s)EP14196763.8  / EP2865382
The date of the Examining Division's first communication in respect of the earliest application for which a communication has been issued is  19.12.2013
Opposition(s)Opponent(s)01  07.08.2015  08.09.2015  ADMISSIBLE
Société des Produits Nestlé S.A.
Avenue Nestlé 55
1800 Vevey / CH
Opponent's representative
Rupp, Christian
Mitscherlich PartmbB
Patent- und Rechtsanwälte
Sonnenstraße 33
80331 München / DE
 02  15.09.2015  21.09.2015  ADMISSIBLE
Groupe Lactalis
10 rue Adolphe Beck
53000 Laval / FR
Opponent's representative
Cabinet Le Guen Maillet
3, impasse de la Vigie
CS 71840
35418 Saint-Malo Cedex / FR
 [2019/30]
Former [2016/16]
Opponent(s)01  07.08.2015  08.09.2015  ADMISSIBLE
Nestec S.A.
Avenue Nestlé 55
1800 Vevey / CH
Opponent's representative
Rupp, Christian
Mitscherlich PartmbB
Patent- und Rechtsanwälte
Sonnenstraße 33
80331 München / DE
 02  15.09.2015  21.09.2015  ADMISSIBLE
Groupe Lactalis
10 rue Adolphe Beck
53000 Laval / FR
Opponent's representative
Le Guen-Maillet
5, place de Newquay
BP 70250
35802 Dinard Cedex / FR
Former [2015/43]
Opponent(s)01  07.08.2015  08.09.2015  ADMISSIBLE
Nestec S.A.
Avenue Nestlé 55
1800 Vevey / CH
Opponent's representative
Rupp, Christian
Mitscherlich PartmbB
Patent- und Rechtsanwälte
Sonnenstraße 33
80331 München / DE
 02  15.09.2015   
Groupe Lactalis
10 rue Adolphe Beck
53000 Laval / FR
Opponent's representative
Maillet, Alain
Cabinet Le Guen Maillet
5, place Newquay
B.P. 70250
35802 Dinard Cedex / FR
Former [2015/38]
Opponent(s)01  07.08.2015   
Nestec S.A.
Avenue Nestlé 55
1800 Vevey / CH
Opponent's representative
Rupp, Christian
Mitscherlich PartmbB
Patent- und Rechtsanwälte
Sonnenstraße 33
80331 München / DE
deletedDeletion: Legal effect of rejection of opposition [ N /P ]
26.10.2015Invitation to proprietor to file observations on the notice of opposition
01.03.2016Reply of patent proprietor to notice(s) of opposition
30.11.2016Date of oral proceedings
23.12.2016Despatch of minutes of oral proceedings
23.12.2016Date of despatch of rejection of opposition
Appeal following opposition31.01.2017Appeal received No.  T0292/17
13.04.2017Statement of grounds filed
Fees paidRenewal fee
17.12.2012Renewal fee patent year 03
16.12.2013Renewal fee patent year 04
Lapses during opposition  TooltipHU23.12.2010
AL17.12.2014
AT17.12.2014
BG17.12.2014
CY17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
MK17.12.2014
MT17.12.2014
PT17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
LU23.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
[2018/46]
Former [2018/30]HU23.12.2010
AT17.12.2014
BG17.12.2014
CY17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
MK17.12.2014
MT17.12.2014
PT17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
LU23.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/33]HU23.12.2010
AT17.12.2014
BG17.12.2014
CY17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
MT17.12.2014
PT17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
LU23.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/32]HU23.12.2010
AT17.12.2014
BG17.12.2014
CY17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
PT17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/31]AT17.12.2014
BG17.12.2014
CY17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
PT17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/30]AT17.12.2014
BG17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
PT17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/28]AT17.12.2014
BG17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/22]AT17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
SM17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2016/12]AT17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
RO17.12.2014
RS17.12.2014
SI17.12.2014
SK17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2015/50]AT17.12.2014
CZ17.12.2014
DK17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
RO17.12.2014
RS17.12.2014
SK17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2015/43]AT17.12.2014
CZ17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
MC17.12.2014
RO17.12.2014
RS17.12.2014
SK17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2015/38]AT17.12.2014
CZ17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
RO17.12.2014
RS17.12.2014
SK17.12.2014
NO17.03.2015
GR18.03.2015
IS17.04.2015
Former [2015/37]CZ17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
RO17.12.2014
RS17.12.2014
SK17.12.2014
NO17.03.2015
GR18.03.2015
Former [2015/36]CZ17.12.2014
EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
RO17.12.2014
RS17.12.2014
NO17.03.2015
GR18.03.2015
Former [2015/35]EE17.12.2014
FI17.12.2014
HR17.12.2014
LV17.12.2014
RS17.12.2014
NO17.03.2015
GR18.03.2015
Former [2015/24]FI17.12.2014
HR17.12.2014
LV17.12.2014
RS17.12.2014
NO17.03.2015
GR18.03.2015
Former [2015/23]FI17.12.2014
NO17.03.2015
Former [2015/21]NO17.03.2015
Cited inInternational search[ID]WO2004056208  (NUTRICIA NV [NL], et al) [ID] 1,10,14,18 * the whole document *;
 [I]WO2007043870  (NUTRICIA NV [NL], et al) [I] 1,10,14,18 * page 3, line 3 - line 8 * * page 4, line 3 - line 10 * * page 6, line 26 - page 7, line 15 *
 [T]  - LUIKING Y C ET AL, "PP203 A HIGH WHEY-PROTEIN LEUCINE-ENRICHED LOW-CALORIC SUPPLEMENT RESULTS IN HIGHER AND FASTER RISE IN SERUM AMINO ACID LEVELS THAN A CASEIN CONTAINING OR HIGH-CALORIC SUPPLEMENT EQUIVALENT", CLINICAL NUTRITION SUPPLEMENTS, ELSEVIER, vol. 5, no. 2, ISSN 1744-1161, (20100101), page 102, (20100101), XP027354617
 [A]  - VAN NORREN K ET AL, "P146 MUSCLE FUNCTION AND DAILY ACTIVITY IN TUMOUR-BEARING CACHECTIC MICE IMPROVE FOLLOWING DIETARY SUPPLEMENTATION WITH A NEW COMPLEX OF HIGH PROTEIN, LEUCINE AND FISH OIL", CLINICAL NUTRITION SUPPLEMENTS, ELSEVIER, vol. 3, ISSN 1744-1161, (20080101), pages 90 - 91, (20080101), XP025348555 [A] 1
 [A]  - RIEU ET AL, "Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats", NUTRITION, ELSEVIER INC, US, (20070330), vol. 23, no. 4, doi:DOI:10.1016/J.NUT.2006.12.013, ISSN 0899-9007, pages 323 - 331, XP022009607 [A] 1 * abstract * * table 1 *

DOI:   http://dx.doi.org/10.1016/j.nut.2006.12.013
 [A]  - CROZIER S J ET AL, "Oral leucine administration stimulates protein synthesis in rat skeletal muscle", JOURNAL OF NUTRITION, WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, PHILADELPHIA, PA, US, (20050101), vol. 135, no. 3, ISSN 0022-3166, pages 376 - 382, XP002427446 [A] 1
 [A]  - KOOPMAN ET AL, "Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protien synthesis in vivo in male subjects", AMERICAN JOURNAL OF PHYSIOLOGY: ENDOCRINOLOGY AND METABOLISM, AMERICAN PHYSIOLOGICAL SOCIETY, BETHESDA, MD, US, (20040101), vol. 288, doi:DOI:10.1152/AJPENDO.00413.2004, ISSN 0193-1849, pages E645 - E653, XP002415349 [A] 1

DOI:   http://dx.doi.org/10.1152/ajpendo.00413.2004
Examination   - SOUCI, FACHMAN, KRAUT, Food Composition and Nutrition Tables, pages 562 - 563
    - Anonymous, "Cocoa Powder", Swiss Food Composition Database V 5.0, (20140303), URL: http://naehrwertdaten.ch/request?query=ProductDetails&xml=MessageData&xml=MetaData&pdf=PdfOutput&productId=7206&lan=en&pageKey=Pdf, (20140303), XP055105138
    - Cocoa powder Oil partially removed // Kakaopulver schwach entölt // Cacao en poundre légèrement déshuilé ED - Souci Siegfried Walter; Fachmann Walter; Kraut Heinrich; Scherz Heimo; Senser Friedrich, FOOD COMPOSITION AND NUTRITION TABLES = DIE ZUSAMMENSETZUNG DER LEBENSMITTEL, NÄHRWERT-TABELLEN = LA COMPOSITION DES ALIMENTS, TABLEAUX DES VALEURS NUTRITIVES, MEDPHARM SCIENTIFIC PUBLISHERS, STUTTGART, GERMANY, PAGE(S) 1113, (20000101), ISBN 978-3-88763-076-8, XP002696871
by applicantWO2005039597
 WO0160378
 WO2009113858
    - ROLLAND, Y. ET AL., "Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives", J NUTR HEALTH AGING, (2008), vol. 12, no. 7, pages 433 - 50
    - SHORT, K.R.; K.S. NAIR, "Mechanisms of sarcopenia of aging", J ENDOCRINOL INVEST, (1999), vol. 22, no. 5, pages 95 - 105
    - BOIRIE, Y., "Physiopathological mechanism of sarcopenia", J NUTR HEALTH AGING, (2009), vol. 13, no. 8, pages 717 - 23
    - GUILLET, C. ET AL., "Impaired anabolic response of muscle protein synthesis is associated with S6Kl dysregulation in elderly humans", FASEB J, (2004), vol. 18, no. 13, pages 1586 - 7
    - RASMUSSEN, B.B. ET AL., "Insulin resistance of muscle protein metabolism in aging", FASEB J, (2006), vol. 20, no. 6, pages 768 - 9
    - CUTHBERTSON, D. ET AL., "Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle", FASEB J, (2005), vol. 19, no. 3, pages 422 - 4
    - BOIRIE, Y. ET AL., "Slow and fast dietary proteins differently modulate postprandial protein accretion", PROC NATL ACAD SCI U S A, (1997), vol. 94, no. 26, doi:doi:10.1073/pnas.94.26.14930, pages 14930 - 5, XP002099786

DOI:   http://dx.doi.org/10.1073/pnas.94.26.14930
    - KATSANOS, C.S. ET AL., "A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly", AM J PHYSIOL ENDOCRINOL METAB, (2006), vol. 291, no. 2, doi:doi:10.1152/AJPENDO.00488.2005, pages E381 - 7, XP002667571

DOI:   http://dx.doi.org/10.1152/AJPENDO.00488.2005
    - VOLPI, E. ET AL., "Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults", AM J CLIN NUTR, (2003), vol. 78, no. 2, pages 250 - 8, XP002609729
    - PADDON-JONES, D. ET AL., "Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein", EXP GERONTOL, (2006), vol. 41, no. 2, doi:doi:10.1016/j.exger.2005.10.006, pages 215 - 9, XP025083241

DOI:   http://dx.doi.org/10.1016/j.exger.2005.10.006
    - KATSANOS, C.S. ET AL., "Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids", AM J CLIN NUTR, (2005), vol. 82, no. 5, pages 1065 - 73
    - PADDON-JONES, D. ET AL., "Amino acid ingestion improves muscle protein synthesis in the young and elderly", AM J PHYSIOL ENDOCRINOL METAB, (2004), vol. 286, no. 3, pages E321 - 8
    - ANTHONY, J.C. ET AL., "Leucine stimulates translation initiation in skeletal muscle of postab- sorptive rats via a rapamycin-sensitive pathway", J NUTR, (2000), vol. 130, no. 10, pages 2413 - 9
    - RIEU, I. ET AL., "Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats", NUTRITION, (2007), vol. 23, no. 4, doi:doi:10.1016/j.nut.2006.12.013, pages 323 - 31, XP022009607

DOI:   http://dx.doi.org/10.1016/j.nut.2006.12.013
    - DANGIN, M. ET AL., "The rate of protein digestion affects protein gain differently during aging in humans", J PHYSIOL, (2003), vol. 549, no. 2, pages 635 - 44
    - BOHE, J. ET AL., "Human muscle protein synthesis is modulated by extracellular, not intramuscular amino acid availability: a dose-response study", J PHYSIOL, (2003), vol. 552, no. 1, pages 315 - 24
    - WOLFE, R.R., "Protein supplements and exercise", AM J CLIN NUTR, (2000), vol. 72, no. 2, pages 551S - 7S
    - MARIEB, E.N., Human anatomy & Physiology, MENLO PARK, CALIFORNIA: BENJA- MIN/CUMMINGS SCIENCE PUBLISHING, (1998), page 1192
    - DANGIN, M. ET AL., "Influence of the protein digestion rate on protein turnover in young and elderly subjects", J NUTR, (2002), vol. 132, no. 10, pages 3228S - 33S
    - DANGIN, M. ET AL., "The digestion rate of protein is an independent regulating factor of postprandial protein retention", AM J PHYSIOL ENDOCRINOL METAB, (2001), vol. 280, no. 2, pages E340 - 8
    - BOIRIE, Y.; P. GACHON; B. BEAUFRERE, "Splanchnic and whole-body leucine kinetics in young and elderly men", AM J CLIN NUTR, (1997), vol. 65, no. 2, pages 489 - 95
    - VOLPI, E. ET AL., "Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction", AM J PHYSIOL, (1999), vol. 277, pages E513 - 20
    - CLARKSTON, W.K. ET AL., "Evidence for the anorexia of aging: gastrointestinal transit and hunger in healthy elderly vs. young adults", AM J PHYSIOL, (1997), vol. 272, pages R243 - 8
    - HOLICK, M.F., VITAMIN D DEFICIENCY. N ENGL J MED, (2007), vol. 357, no. 3, pages 266 - 81
    - LESSER, S. ET AL., "Nutritional situation of the elderly in Eastern/Baltic and Central/Western Europe - the AgeingNutrition project", ANN NUTR METAB, (2008), vol. 52, no. 1, pages 62 - 71
    - BARTALI, B. ET AL., "Low nutrient intake is an essential component of frailty in older persons", J GERONTOL A BIOL SCI MED SCI, (2006), vol. 61, no. 6, pages 589 - 93
    - SEMBA, R.D. ET AL., "ow serum micronutrient concentrations predict frailty among older women living in the community", J GERONTOL A BIOL SCI MED SCI, (2006), vol. 61, no. 6, pages 594 - 9
    - MARZANI, B. ET AL., "Antioxidant supplementation restores defective leucine stimulation of protein synthesis in skeletal muscle from old rats", J NUTR, (2008), vol. 138, no. 11, doi:doi:10.3945/jn.108.094029, pages 2205 - 11, XP055017105

DOI:   http://dx.doi.org/10.3945/jn.108.094029
    - BISCHOFF-FERRARI, H.A. ET AL., "Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y", AM J CLIN NUTR, (2004), vol. 80, no. 3, pages 752 - 8
    - BISCHOFF-FERRARI, H.A. ET AL., "Prevention of non vertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials", ARCH INTERN MED, (2009), vol. 169, no. 6, pages 551 - 61
    - BISCHOFF-FERRARI, H.A. ET AL., "Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials", BMJ, (2009), vol. 339, page B3692
    - SESHADRI, S. ET AL., "Plasma homocysteine as a risk factor for dementia and Alzheimer's disease", N ENGL J MED, (2002), vol. 346, no. 7, pages 476 - 83
    - VOLPI, E. ET AL., "Exogenous amino acids stimulate net muscle protein synthesis in the elderly", J CLIN INVEST, (1998), vol. 101, no. 9, pages 2000 - 7, XP002609730
    - RIEU, I. ET AL., "Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia", J PHYSIOL, (2006), vol. 575, no. 1, pages 305 - 15