2. Present Participants of Working Group (countries, names):

J. Eckel (Germany), P. Shepherd (UK), K. Siddle (UK), L. Hue (Belgium), M.H. Rider (Belgium), F. Giorgino (Italy), M. Simionescu (Romania), R. Zorec (Slovenia), C. Reynet (Denmark), A. Handberg (Denmark), A.C. Rustan (Norway), J. Jensen (Norway), E. Sebokova (Slovakia), I. Klimes (Slovakia), M. Ouwens (Netherlands), J.A. Maassen (Netherlands), J.R. Zierath (Sweden), G. Dimitriadis (Greece), A. Zorzano (Spain), M. Lorenzo (Spain), J.J. Nolan (Israel)

3. Agenda of Working Group (topics to be addressed, methods):

·        study the impact of age, primary and secondary insulin resistance, exercise, adrenaline, and fatty acids on the expression and function of transporting and signalling proteins important for substrate uptake and processing in skeletal muscle

·        biological factors behind muscle differentiation

·         combined cellular and physiological approach using different muscle-specific transgenic mouse models (AMPK,...).

·         co-culture of human adipocytes and human skeletal muscle cells for studies on the pathogenesis of insulin resistance

4. Joint Actions Planned (collaborations between more than two labs in the Working Group, participants and topics listed):
At present:

·        Signaling through insulin and IGF1 receptors: K. Siddle (UK), C. Reynet (Denmark), A. Handberg (Denmark), J.A. Maassen (Netherlands), A.C. Rustan (Norway)

·        Molecular, cellular and metabolic perspectives of insulin resistance using human skeletal muscle cells in culture: A. Handberg (Denmark), C. Reynet (Denmark), A. C. Rustan (Norway), J. Jensen (Norway), J.R. Zierath (Sweden), P. Shepherd (UK), A. Zorzano (Spain), J.Eckel (Germany)

·        Critical role of AMPK: J.R. Zierath (Sweden), L. Hue (Belgium), M.H. Rider (Belgium), A.C. Rustan (Norway)

5. Planned Bilateral Collaborations (participants and topics listed):

·         Collaboration with “Glucose Transport and Ageing” WG need to be developed and with “Drugs and New Preventive Therapeutic Approaches to improve Glucose metabolism and Clinical Insulin Resistance” WG need to be established.

·         Joint Action recently established with Cardiovascular WG5: organization of a joint working group meeting in Bucarest in October 2002.

·         Need to discuss of possibilities on joint action on interactions between muscle and fat.

6. Proposed Methods to Increase the “Action Potential” and “Visibility” of the Working Group:

·         Increase the Action potential by leaving much more time for discussion (after every presentation, but also during the breaks) during the WG meetings/workshops, especially when most of the participants of the Action are present because of a concomitant management committee meeting.

·         Develop joint actions by organizing working group meetings with few but very focused topics.

·         Increase visibility by presenting orally a short progress report of the interaction within the WG and between the WGs during the management committee meetings.

7. Planned Meetings (approximate date, place, topics):

·         No small WG meeting has been planned officially yet, but continuous communication and meeting between the different collaborators, especially during international scientific congresses.

·         The previously planned Working Group/ Workshop Meeting in Copenhagen, November or December 2002 on “Skeletal Muscle Metabolism: Regulation, Exercise, Diabetes” (with interaction with Copenhagen Muscle Research Centre (CMRC), Copenhagen, DK) has been replaced by the organization of a combined WG3-5 Working Group Meeting on “Cardiac/Skeletal Muscle and Ageing” in Bucarest (RO) in October 2002 - Main Organizer: M. Simionescu (RO)

1. Name of Working Group: WG4 “Drugs and New Preventive Therapeutic Approaches To Improve Glucose Metabolism and Clinical Insulin Resistance”

2. Present Participants of Working Group (countries, names):

B. Bendlova (CZ), P. Csermely (H), G. Dimitriadis (GR), J. Eckel (D), J. Eriksson (S), F. Giorgino (I), A. Handberg (DK), L. Hue (B), J. Jensen (N), G. Jermendy (H), M. Lorenzo (E), V. Matulevicius (LT), D. Popov (RO), C. Reynet (DK), M. H. Rider (B), A. Rustan (N), S. Sasson (IL), E. Sebokova (SK), P. Shepherd (UK), M. Simionescu (RO), J. R. Zierath (S), A. Zorzano (E), V. Urbanavicius (LT), I. Varela-Nieto (E),  N. Bashan (IL)

3. Agenda of Working Group (topics to be addressed, methods):

        Study of insulin action and insulin resistance at molecular and clinical levels; identification of critical signaling intermediates for glucose utilization; investigation of molecules that act as stimulators of glucose utilization or targets for drugs known to regulate this process; clarification of the mechanism of action of insulin-sensitizing drugs; gene therapy of insulin resistance.

        Investigation of indexes of insulin resistance in ageing people; validation of surrogate markers for in vivo insulin sensitivity; creation of transgenic animals mimicking human models of insulin resistance.

        To accomplish the above goals this WG will work in cooperation with all other WG of the action (genetics, glucose transport, muscle, cardiovascular) and act to develop the therapeutic implications of the activities of each WG and provide contacts with pharmacological and biotechnology industries to pursue therapeutic outcomes.

4. Joint Actions Planned (collaborations between more than two labs in the Working Group, participants and topics listed):

            Insulin signaling to glucose transport / novel glucose transport regulatory mechanisms

            Non-insulin signaling related mechanisms for glucose transport stimulation

            Mechanism of action of insulin sensitizers

            Tissue determinants of in vivo insulin resistance

            Pharmaceutical control of glucose metabolism through regulation of gene expression

5. Planned Bilateral Collaborations (participants and topics listed):

·        Joint Action 1: interaction with WG on “Glucose Transport and Ageing”. Joint meeting in November 2002 in Bari, Italy (see below).

·        Joint Action 2: collaboration with WG on “Muscle and Ageing” established.

·        Joint Action 3: collaboration with WG on “Genetics” on diabetes subphenotypes and pharmacological therapy (needs to be established).

6. Proposed Methods to Increase the “Action Potential” and “Visibility” of the Working Group:

·        Facilitate and support interaction with pharmaceutical industries.

·        Advertisement of WG meetings on the web. Highlight projects on novel regulatory mechanisms, markers of insulin resistance, and drugs being investigated.

·        The COST B17 meeting in Bari, Italy, on “Trafficking of Glucose Transporters and Insulin Signaling Proteins – 1^st International Conference on Molecular Basis of Metabolic Regulation” was covered by local and national newspapers and TVs. In addition, this meeting involved scientists from North America and Australia plus additional non-COST scientist who learned about COST B17 action and its activities.

7. Planned Meetings (approximate date, place, topics):

·        No small WG meeting has been planned officially yet, but continuous communication and meeting between the different collaborators, especially during international scientific meetings.

§ A Joint Working Group meeting of WG2 (Glucose and other Transport Processes and Ageing) and WG4 (Drugs and New Preventive Therapeutic Approaches to Improve Glucose Metabolism and Insulin Resistance) on “Trafficking of Glucose Transporters and Signaling Molecules” was organized in Bari, Italy, on November 15-16, 2002 by F. Giorgino (Italy). The main topics were trafficking of glucose transporters and other membrane transporters, signaling specificity through protein compartmentalization, tissue specificity and insulin signaling, trafficking defects and insulin resistance, pharmaceutical targets to improve insulin action and glucose metabolism.

§ Another meeting of WG4 will take place (likely in 2004) to cover the more clinical aspects of this WG.

1. Name of Working Group: WG5, Cardiovascular dysfunctions

2. Present Participants of Working Group (countries, names):

Romania – Professor Maya Simionescu,

Professor Dan Cheta,

Dr. Doina Popov,

            Dr. Dorel Radu

Dr. Elena Ganea

UK – Dr. Peter Shepherd

Israel – Professor Shlomo Sasson, Prof. Nava Bashan

Germany – Professor Juergen Eckel

Norway- Dr. Jorgen Jensen

Italy- Professor Francesco Giorgino

3. Agenda of Working Group (topics to be addressed, methods):

·        effects of high glucose on the signaling pathways of the cells of the vascular wall;

·        effects of hypercaloric diet on hamster, as an experimental model for mild diabetes

·        the possible roles of leptin in cardiovascular function

·        insulin glycation

4. Joint Actions Planned (collaborations between more than two labs in the Working Group, participants and topics listed):

At 10-13 October 2002 the Institute of Cellular Biology and Pathology "N.Simionescu", Center of Excellence of the European Community" hosted the Meeting of the COST B17 Action Working group "Cardiovascular dysfunction" jointly with the Workshop on "Cardiovascular dysfunction in hyperlipidemia and diabetes". The latter was organized within the frame of Centers of Excellence of the European Community.

These meetings consisted in: 31 platform presentations (followed by ample discussions), 30 posters displayed throughout  the Meeting, the visit of the Institute, and a Pannel discussion moderated by Prof. M. Pascu, the Representative of the European Commission, COST Cooperation: Medicine and Health (Brussells, Belgium). The Meeting was an excellent opportunity for presentation of new scientific data and interactive discussions of the results between the 17 prominent Professors from Universities and Research Institutes from 11 European countries, and the 15 Romanian Professors, research scientists, and Ph.D students. Among the 150 participants there were numerous students, Ph. students and postgraduate students in the audience.

The goals of the Meeting: scientific interaction and in-depth understanding of the knowledge in the today's cardiovascular pathology with a special focus on atherosclerosis, diabetes and their complications; initiatives for collaboration in complementary research projects; establishment of networks and Consortia within the Sixth Framework Program; discussion about methods and means to increase visibility of the Centers of Excellence of the European Community, and of the COST Working group "Cardiovascular dysfunction".

The main scientific topics discussed were: (i) the alteration of the normal function of the cells of the vascular wall under the harmful effect of hyperlipidemia and/or hyperglycemia that induce several changes such as: "endothelial dysfunction", "endothelial activation", inflammatory processes, and intense oxidative stress that in turn induces severe metabolic imbalances; (ii) identification of the genetic markers that predispose people to cardiovascular diseases; (iii) identification and understanding the signal transduction pathways that are activated in vascular cells and in circulating blood cells by insulin and leptin (a hormone that regulates appetite and hence is involved in obesity) stimulation, (iv) testing the efficiency of new drugs for atherosclerosis/diabetes by investigations conducted at cellular and molecular level.

The results of the scientific Meeting: setting up common collaborative projects, identification of the topics were Romanian scientific expertise is complementary to that of the foreign laboratories, the testing of new drugs that may potentially help to slow down/stop the functional and metabolic imbalances associated with hyperlipidemia/diabetes, direct contact with the expertise of the Institute of Cellular Biology and Pathology "N.Simionescu" It was concluded that high level biomedical research has to be performed in depth, and that studies on cell pathology, biochemistry and the genetic determinants will lead to the understanding of the deviation of the regulatory processes - the only way to conduct to the prevention or slowing down of the disturbances installed during atherosclerosis and diabetes.

5. Planned Bilateral Collaborations (participants and topics listed):

·        Collaboration of Institute of Cellular Biology and Pathology “N.Simionescu” (Bucharest, Romania) with University College of London,  Department of Biochemistry (UK) on studies on the effects of lipids, glucose and leptin on the cardiovascular system.

·        Collaboration of the laboratory "Posttranslational modifications of proteins" from the Institute of Biochemistry, Bucharest, Romania with the University of Rhode Island, Kingston, USA, Dept. of Chemistry, on the inhibitory effects of various compounds on early or advanced glycation products formation.

·        Other interactions/discussions on topics of common interest, that may conduct to complementary experimental approaches in common projects.

6. Proposed Methods to Increase the “Action Potential” and “Visibility” of the Working Group:

·        Professor Maya Simionescu proposed to scientists in cardiovascular research (those of WG5 of COST included) the publication of a book entitled "CELLULAR DYSFUNCTION IN CARDIOVASCULAR DISEASES AND DIABETES: REPORTS FROM BENCH TO BEDSIDE"

·        Dr. Dan Cheta is proposing an editorial project with the tentative title "VASCULAR IMPLICATION IN DIABETES. Clinical and Experimental", for 2003.

·        Presentation of short progress reports on topics and interaction within WGs at the Management Committee Meetings.

7. Planned Meetings (approximate date, place, topics):

·        Fall 2003 - Organizers: M. Simionescu, Doina Popov (Romania)