Welcome in the research database

Diabetes/Genetics/Development/Transplantation

Our group is interested in defining the factors (nutrients,hormones,neuropeptides,...) which determine the regulation of the genes coding to the majors hormones involved in glucose homeostasis, insulin and glucagons, the mechanisms by which they exert their effects and the transcription factors involved.

Development and differentiation of glucagon-producing cells in the endocrine pancreas:
The mechanisms by which the glucagon-producing cells appear and differentiate are unclear.Our hypothesis is that these cells develop by a default pathway, in the absence of beta and delta cell-specific factors, such as Pdx-1 and Pax-4 which are critical for the development of these 2 cell types. We investigate this hypothesis by studies both in cell lines and transgenic animals.

Molecular basis of diabetes:
We have investigated the genetic basis of MODY (Maturity-Onset Diabetes of the Young) in Switzerland as well the molecular basis of cases of pancreas agenesis and severe insulin resistance. We are pursuing this analysis of human gene defects involved in disorders of glucose homeostasis.

Molecular diagnosis of islet graft rejection in humans:
The diagnosis of islet graft rejection is presently impossible.We have designed a molecular marker which reflects beta cell loss after islet transplantation. We are currently investigating whether this test is sensitive and clinically adequate to diagnose rejection of islet transplantation.

Group's publications

Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark.
AMERICAN JOURNAL OF TRANSPLANTATION
2009 vol. 9(2) pp. 419-423
BERNEY T, FERRARI-LACRAZ SYLVIE, BUEHLER LH, OBERHOLZER J, MARANGON NICOLA, PHILIPPE J, VILLARD J, MOREL P

Treating type 2 diabetes: how safe are current therapeutic agents?
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
2009 vol. 63(2) pp. 321-332
PHILIPPE J, RACCAH D

Portable multi-anvil device for in situ angle-dispersive synchrotron diffraction measurements at high pressure and temperature.
JOURNAL OF SYNCHROTRON RADIATION
2009 vol. 16(Pt 4) pp. 513-523
LE GODEC Y, HAMEL G, SOLOZHENKO VL, MARTIVEZ-GARCIA D, PHILIPPE J, HAMMOUDA T, MEZOUAR M, CRICHTON WA, MORARD G, KLOTZ S

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6).
LANCET
2009 vol. 374(9683) pp. 39-47
BUSE JB AND AL.

Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2.
MOLECULAR AND CELLULAR BIOLOGY : MCB
2009 vol. 29(8) pp. 2322-2334
KATZ L, GOSMAIN Y, MARTHINET E, PHILIPPE J

Mucocutaneous papillomatous papules in Cowden's syndrome.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
2008 vol. 33(2) pp. 151-153
JORNAYVAZ FR, PHILIPPE J

Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial.
DIABETES, OBESITY AND METABOLISM
2008 vol. 10(5) pp. 387-399
DAVIES M AND AL

Motesanib diphosphate in progressive differentiated thyroid cancer.
NEW ENGLAND JOURNAL OF MEDICINE
2008 vol. 359(1) pp. 31-42
SHERMAN SI AND AL

The beta-cell specific transcription factor Nkx6.1 inhibits glucagon gene transcription by interfering with Pax6
BIOCHEMICAL JOURNAL
2007 vol. 403(3) pp. 593-601
GAUTHIER BENOIT R., GOSMAIN YVAN, MAMIN ALINE, PHILIPPE JACQUES

Insulin resistance treatments in the future
JOURNAL DE LA SOCIETE DE BIOLOGIE
2007 vol. 201(2) pp. 155-158
PHILIPPE J, JORNAYVAZ F

Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression
JOURNAL OF BIOLOGICAL CHEMISTRY
2007 vol. 282 pp. 35024-35034
GOSMAIN Y, AVRIL I, MAMIN A, PHILIPPE J

Activin A decreases glucagon and arx gene expression in alpha-cell lines
MOLECULAR ENDOCRINOLOGY
2007 vol. 21 pp. 259-273
MAMIN A, PHILIPPE J

Diabetes mellitus and driving
REVUE MÉDICALE SUISSE
2007 vol. 3(114) pp. 1437-1441
JORNAYVAZ FR, RAGUSO CA, PHILIPPE J

Physical activity in the prevention and control of diabetes
REVUE MÉDICALE SUISSE
2007 vol. 3(114) pp. 1442-1448
RAGUSO CA, SPADA A, JORNAYVAZ FR, PHILIPPE J

The diabetic patient at altitude: pathophysiology and practical implications
REVUE MÉDICALE SUISSE
2007 vol. 3(114) pp. 1463-1466
THALMANN S, GOJANOVIC B, JORNAYVAZ FR, GREMION G, PHILIPPE J

Detection of insulin mRNA in the peripheral blood after human islet transplantion predicts deterioration of metabolic control
AMERICAN JOURNAL OF TRANSPLANTATION
2006 vol. 6 pp. 1704-1711
BERNEY T, MAMIN A, SHAPIRO AMJ, RITZ-LASER B, BRULHART MC, TOSO C, DEMUYLDER-MISCHLER S, ARMANET M, BAERTSCHIGER R, WOJTUSCISZYN A, BENHAMOU PY, BOSCO D, MOREL P, PHILIPPE J

Sequential kidney/islet transplantation: efficacy and safety assessment of a steroid-free immunosuppression protocol
AMERICAN JOURNAL OF TRANSPLANTATION
2006 vol. 6(5 Pt 1) pp. 1049-1058
TOSO C. ET AL.

Management of diabetes: a priority for the European Union
REVUE MÉDICALE SUISSE
2006 vol. 2(68) pp. 1443-1443
RUIZ J, PHILIPPE J

Should we treat all diabetic patients with aspirin in primary prevention
REVUE MEDICALE DE LA SUISSE ROMANDE
2005 vol. 1(22) pp. 1500-1504

The evolution of obesity
REVUE MEDICALE DE LA SUISSE ROMANDE
2005 vol. 1(22) pp. 1475-1476

Islet of Langerhans allogeneic transplantation at the University of Geneva in the steroid free era in islet after kidney and simultaneous islet-kidney transplantations
TRANSPLANTATION PROCEEDINGS
2004 vol. 36 pp. 1121-1122
BERNEY T, BUCHER P, MATHE Z, ANDRES A, BOSCO D, MAGE R, TOSO C, OBERHOLZER J, BECKER C, PHILIPPE JACQUES, BUHLER L, MOREL P

Ectopic expression of the beta-cell specific transcription factor Pdx1 inhibits glucagon gene transcription.
DIABETOLOGIA
2003 vol. 46(6) pp. 810-821
RITZ-LASER B, GAUTHIER BR, ESTREICHER VON ROZBIERSKI A, MAMIN A, BRUN T, RIS F, SALMON P, HALBAN PA, TRONO D, PHILIPPE J

Agenesis of human pancreas due to decreased half-life of insulin promoter factor I
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
2003 vol. 88 pp. 4398-4406
SCHWITZGEBEL V, MAMIN A, BRUN T, RITZ-LASER B, ZAIKO M, MARET A, THEINTZ GE, MICHIELIN O, MELLOUL D, PHILIPPE J

Molecular detection of circulating beta-cells after islet transplantation
DIABETES
2002 vol. 51 pp. 557-561
RITZ-LASER B, OBERHOLZER J, TOSO C, BRULHART MC, ZAKRZEWSKA K, RIS F, BUCHER P, MOREL P, PHILIPPE J

Hepatic nuclear factors-3 (HNF-3 or Foxa2) regulates glucagon gene transpcription by binding to the G1 and G2 prometer elements
MOLECULAR ENDOCRINOLOGY
2002 vol. 16 pp. 170-183
GAUTHIER BR, SCHWITZGEBEL VM, ZAIKO M, MAMIN A, RITZ-LASER B, PHILIPPE J

The paired homeodomain transcription factor Pax-2 is expressed in the endocrine pancreas and transactivates the glucagons gene promoter
JOURNAL OF BIOLOGICAL CHEMISTRY
2000 vol. 275 pp. 32708-32715

Research's domains

TRANSPLANTATION
MOLECULAR BIOLOGY
GENETIC
DIABETE




DATABASE-RESEARCH	GROUP OF CLINICAL BIOLOGY RESEARCH

Jacques PHILIPPE	Head of group CV	Research subject	Members of the group


	Links about the group Prof PHILIPPE J HUG/Spécialités de Médecine Serv. Endo.Diabet.Nutrit. Rue Gabrielle-Perret-Gentil 4 1211 Genève 14 Suisse Jacques.Philippe@hcuge.ch Tel.: 022 372 42 37 / 022 372 92 99 Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Diabetes/Genetics/Development/Transplantation Our group is interested in defining the factors (nutrients,hormones,neuropeptides,...) which determine the regulation of the genes coding to the majors hormones involved in glucose homeostasis, insulin and glucagons, the mechanisms by which they exert their effects and the transcription factors involved. Development and differentiation of glucagon-producing cells in the endocrine pancreas: The mechanisms by which the glucagon-producing cells appear and differentiate are unclear.Our hypothesis is that these cells develop by a default pathway, in the absence of beta and delta cell-specific factors, such as Pdx-1 and Pax-4 which are critical for the development of these 2 cell types. We investigate this hypothesis by studies both in cell lines and transgenic animals. Molecular basis of diabetes: We have investigated the genetic basis of MODY (Maturity-Onset Diabetes of the Young) in Switzerland as well the molecular basis of cases of pancreas agenesis and severe insulin resistance. We are pursuing this analysis of human gene defects involved in disorders of glucose homeostasis. Molecular diagnosis of islet graft rejection in humans: The diagnosis of islet graft rejection is presently impossible.We have designed a molecular marker which reflects beta cell loss after islet transplantation. We are currently investigating whether this test is sensitive and clinically adequate to diagnose rejection of islet transplantation. Group's publications Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark. AMERICAN JOURNAL OF TRANSPLANTATION 2009 vol. 9(2) pp. 419-423 BERNEY T, FERRARI-LACRAZ SYLVIE, BUEHLER LH, OBERHOLZER J, MARANGON NICOLA, PHILIPPE J, VILLARD J, MOREL P Treating type 2 diabetes: how safe are current therapeutic agents? INTERNATIONAL JOURNAL OF CLINICAL PRACTICE 2009 vol. 63(2) pp. 321-332 PHILIPPE J, RACCAH D Portable multi-anvil device for in situ angle-dispersive synchrotron diffraction measurements at high pressure and temperature. JOURNAL OF SYNCHROTRON RADIATION 2009 vol. 16(Pt 4) pp. 513-523 LE GODEC Y, HAMEL G, SOLOZHENKO VL, MARTIVEZ-GARCIA D, PHILIPPE J, HAMMOUDA T, MEZOUAR M, CRICHTON WA, MORARD G, KLOTZ S Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). LANCET 2009 vol. 374(9683) pp. 39-47 BUSE JB AND AL. Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2. MOLECULAR AND CELLULAR BIOLOGY : MCB 2009 vol. 29(8) pp. 2322-2334 KATZ L, GOSMAIN Y, MARTHINET E, PHILIPPE J Mucocutaneous papillomatous papules in Cowden's syndrome. CLINICAL AND EXPERIMENTAL DERMATOLOGY 2008 vol. 33(2) pp. 151-153 JORNAYVAZ FR, PHILIPPE J Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial. DIABETES, OBESITY AND METABOLISM 2008 vol. 10(5) pp. 387-399 DAVIES M AND AL Motesanib diphosphate in progressive differentiated thyroid cancer. NEW ENGLAND JOURNAL OF MEDICINE 2008 vol. 359(1) pp. 31-42 SHERMAN SI AND AL The beta-cell specific transcription factor Nkx6.1 inhibits glucagon gene transcription by interfering with Pax6 BIOCHEMICAL JOURNAL 2007 vol. 403(3) pp. 593-601 GAUTHIER BENOIT R., GOSMAIN YVAN, MAMIN ALINE, PHILIPPE JACQUES Insulin resistance treatments in the future JOURNAL DE LA SOCIETE DE BIOLOGIE 2007 vol. 201(2) pp. 155-158 PHILIPPE J, JORNAYVAZ F Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression JOURNAL OF BIOLOGICAL CHEMISTRY 2007 vol. 282 pp. 35024-35034 GOSMAIN Y, AVRIL I, MAMIN A, PHILIPPE J Activin A decreases glucagon and arx gene expression in alpha-cell lines MOLECULAR ENDOCRINOLOGY 2007 vol. 21 pp. 259-273 MAMIN A, PHILIPPE J Diabetes mellitus and driving REVUE MÉDICALE SUISSE 2007 vol. 3(114) pp. 1437-1441 JORNAYVAZ FR, RAGUSO CA, PHILIPPE J Physical activity in the prevention and control of diabetes REVUE MÉDICALE SUISSE 2007 vol. 3(114) pp. 1442-1448 RAGUSO CA, SPADA A, JORNAYVAZ FR, PHILIPPE J The diabetic patient at altitude: pathophysiology and practical implications REVUE MÉDICALE SUISSE 2007 vol. 3(114) pp. 1463-1466 THALMANN S, GOJANOVIC B, JORNAYVAZ FR, GREMION G, PHILIPPE J Detection of insulin mRNA in the peripheral blood after human islet transplantion predicts deterioration of metabolic control AMERICAN JOURNAL OF TRANSPLANTATION 2006 vol. 6 pp. 1704-1711 BERNEY T, MAMIN A, SHAPIRO AMJ, RITZ-LASER B, BRULHART MC, TOSO C, DEMUYLDER-MISCHLER S, ARMANET M, BAERTSCHIGER R, WOJTUSCISZYN A, BENHAMOU PY, BOSCO D, MOREL P, PHILIPPE J Sequential kidney/islet transplantation: efficacy and safety assessment of a steroid-free immunosuppression protocol AMERICAN JOURNAL OF TRANSPLANTATION 2006 vol. 6(5 Pt 1) pp. 1049-1058 TOSO C. ET AL. Management of diabetes: a priority for the European Union REVUE MÉDICALE SUISSE 2006 vol. 2(68) pp. 1443-1443 RUIZ J, PHILIPPE J Should we treat all diabetic patients with aspirin in primary prevention REVUE MEDICALE DE LA SUISSE ROMANDE 2005 vol. 1(22) pp. 1500-1504 The evolution of obesity REVUE MEDICALE DE LA SUISSE ROMANDE 2005 vol. 1(22) pp. 1475-1476 Islet of Langerhans allogeneic transplantation at the University of Geneva in the steroid free era in islet after kidney and simultaneous islet-kidney transplantations TRANSPLANTATION PROCEEDINGS 2004 vol. 36 pp. 1121-1122 BERNEY T, BUCHER P, MATHE Z, ANDRES A, BOSCO D, MAGE R, TOSO C, OBERHOLZER J, BECKER C, PHILIPPE JACQUES, BUHLER L, MOREL P Ectopic expression of the beta-cell specific transcription factor Pdx1 inhibits glucagon gene transcription. DIABETOLOGIA 2003 vol. 46(6) pp. 810-821 RITZ-LASER B, GAUTHIER BR, ESTREICHER VON ROZBIERSKI A, MAMIN A, BRUN T, RIS F, SALMON P, HALBAN PA, TRONO D, PHILIPPE J Agenesis of human pancreas due to decreased half-life of insulin promoter factor I JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM 2003 vol. 88 pp. 4398-4406 SCHWITZGEBEL V, MAMIN A, BRUN T, RITZ-LASER B, ZAIKO M, MARET A, THEINTZ GE, MICHIELIN O, MELLOUL D, PHILIPPE J Molecular detection of circulating beta-cells after islet transplantation DIABETES 2002 vol. 51 pp. 557-561 RITZ-LASER B, OBERHOLZER J, TOSO C, BRULHART MC, ZAKRZEWSKA K, RIS F, BUCHER P, MOREL P, PHILIPPE J Hepatic nuclear factors-3 (HNF-3 or Foxa2) regulates glucagon gene transpcription by binding to the G1 and G2 prometer elements MOLECULAR ENDOCRINOLOGY 2002 vol. 16 pp. 170-183 GAUTHIER BR, SCHWITZGEBEL VM, ZAIKO M, MAMIN A, RITZ-LASER B, PHILIPPE J The paired homeodomain transcription factor Pax-2 is expressed in the endocrine pancreas and transactivates the glucagons gene promoter JOURNAL OF BIOLOGICAL CHEMISTRY 2000 vol. 275 pp. 32708-32715 Research's domains TRANSPLANTATION MOLECULAR BIOLOGY GENETIC DIABETE