Diabetes genome anatomy project
19 experiments
1. Human skeletal muscle - type 2 diabetes - Swedish males ( Contact: David Altshuler)
PGC-1alpha-responsive genes involved in oxidative phosphorylation are
coordinately downregulated in human diabetes.
Mootha Vamsi K, Lindgren Cecilia M, Eriksson Karl-Fredrik, Subramanian
Aravind, Sihag Smita, Lehar Joseph, Puigserver Pere, Carlsson Emma, Ridderstrale
Martin, Laurila Esa, Houstis Nicholas, Daly Mark J, Patterson Nick, Mesirov Jill
P, Golub Todd R, Tamayo Pablo, Spiegelman Bruce, Lander Eric S, Hirschhorn Joel
N, Altshuler David, Groop Leif C, Nature genetics. , 2003, 34, 3,
267-73
platform: Affymetrix HG-U133A
No. of chips: 43
Specimen: muscle biopsy of swedish males
Variables: DM (18) vs. IGT (8) vs. Normal (17)
2. Human skeletal muscle - type 2 diabetes and family history positive individuals - Mexican American ( Contact: Mary-Elizabeth Patti)
Coordinated reduction of genes of oxidative metabolism in humans with insulin
resistance and diabetes: Potential role of PGC1 and NRF1.
Patti Mary Elizabeth, Butte Atul J, Crunkhorn Sarah, Cusi Kenneth, Berria
Rachele, Kashyap Sangeeta, Miyazaki Yoshinori, Kohane Isaac, Costello Maura,
Saccone Robert, Landaker Edwin J, Goldfine Allison B, Mun Edward, DeFronzo
Ralph, Finlayson Jean, Kahn C Ronald, Mandarino Lawrence J
Proceedings of the National Academy of Sciences of the United States of
America. , 2003, 100, 14, 8466-71
platform: Affymetrix HuGeneFL
No. of chips: 16
Specimen: muscle biopsy of Mexican American males
Variables: 2 stratum
1. Disease status: Diabetes Mellitus vs. Normal
2. Family history: Diabetic vs. Non-Diabetic Family History
3. Liver - ob/ob mice ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 6
Specimen: liver of ob/ob mice (Leptin Deficient 6-12 week, male, C57BL/6J Mouse Liver) vs. ob/control mice (6-12 week, male, C57BL/6J Mouse Liver)
Variables: ob/ob (3) vs. ob/cont (3), biological replicates
4. Effect of insulin infusion on skeletal muscle ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 12
Specimen: Skeletal muscle of Control male C57BL/6J Mouse infused with saline vs. C57BL/6J male Mouse insulin infused for 15 minutes vs. C57BL/6J male Mouse insulin infused for 60 minutes vs. C57BL/6J male Mouse insulin infused for 180 minutes
Variables: Time series (0min - 15min - 60min - 180min)
5. IR and IRS-1 Single and Double Heterozygous Knockouts - Liver ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 55
Specimen: Liver
Variables: 3 Stratum
1. genetic modifications: IR_Het for IR Heterozygous, Irs-1_Het for Irs-1 Heterozygous, DH for Double Heterozygous, and Wild type for Controls
2. strain: Mouse Strain 129 or C57 Black 6
3. age: 6 months or 6 weeks old
6. IR and IRS-1 Single and Double Heterozygous Knockouts - Skeletal Muscle ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 52
Specimen: Skeletal muscle
Variables: 3 Stratum
1. genetic modifications: IR_Het for IR Heterozygous, Irs-1_Het for Irs-1 Heterozygous, DH for Double Heterozygous, and Wild type for Controls
2. strain: Mouse Strain 129 or C57 Black 6
3. age: 6 months or 6 weeks old
7. IR and IRS-1 Single and Double Heterozygous Knockouts - Epididymal White Fat ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 47
Specimen: Epididymal white fat
Variables: 3 Stratum
1. genetic modifications: IR_Het for IR Heterozygous, Irs-1_Het for Irs-1 Heterozygous, DH for Double Heterozygous, and Wild type for Controls
2. strain: Mouse Strain 129 or C57 Black 6
3. age: 6 months or 6 weeks old
8. Low and High Fat Diet on Mice of Two Genetic Backgrounds (B6 vs. 129) - Fat ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 14
Specimen: Fat
Variables: 2 Stratum
1. Diet: High fat diet vs. Low fat diet
2. Strain: C57Bl/B6 is compared to 129S6/SvEvTac mice
9. Low and High Fat Diet on Mice of Two Genetic Backgrounds (B6 vs. 129) - Skeletal Muscle ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 15
Specimen: Skeletal muscle
Variables: 2 Stratum
1. Diet: High fat diet vs. Low fat diet
2. Strain: C57Bl/B6 is compared to 129S6/SvEvTac mice
10. Low and High Fat Diet on Mice of Two Genetic Backgrounds (B6 vs. 129) - Liver ( Contact: Ronald C Kahn)
platform: Affymetrix MG_U74A
No. of chips: 16
Specimen: Liver
Variables: 2 Stratum
1. Diet: High fat diet vs. Low fat diet
2. Strain: C57Bl/B6 is compared to 129S6/SvEvTac mice
11. Human pancreatic islets from normal and Type 2 diabetic subjects ( Contact: Ronald C Kahn)
Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet
dysfunction in human type 2 diabetes.
Gunton Jenny E, Kulkarni Rohit N, Yim SunHee, Okada Terumasa, Hawthorne Wayne J,
Tseng Yu-Hua, Roberson Russell S, Ricordi Camillo, O'Connell Philip J, Gonzalez
Frank J, Kahn C Ronald, Cell. , 2005, 122, 3, 337-49
platform: Affymetrix HG-U133B
No. of chips: 24
Specimen: Pancreatic islet cells
Variables: 3 Stratum
1. Sex: Male vs. Female
2. Race: Asian vs. Caucasian
3. Disease status: DM vs. normal
12. Transcription profiling of wild type and PGC-1alpha KO liver and skeletal muscle ( Contact: Bruce Spiegelman)
Defects in adaptive energy metabolism with CNS-linked hyperactivity in
PGC-1alpha null mice.
Lin Jiandie, Wu Pei-Hsuan, Tarr Paul T, Lindenberg Katrin S, St-Pierre Julie,
Zhang Chen-Yu, Mootha Vamsi K, J??ger Sibylle, Vianna Claudia R, Reznick Richard
M, Cui Libin, Manieri Monia, Donovan Mi X, Wu Zhidan, Cooper Marcus P, Fan
Melina C, Rohas Lindsay M, Zavacki Ann Marie, Cinti Saverio, Shulman Gerald I,
Lowell Bradford B, Krainc Dimitri, Spiegelman Bruce M
Cell. , 2004, 119, 1, 121-35
platform: Affymetrix MG_U74A
No. of chips: 21
Specimen: Liver or Quadricep (skeletal) muscle
Variables: 3 Stratum
1. Specimen: Liver vs. Quadricep (skeletal) muscle
2. Starvation: Fed vs. Fasted
3. Genetic modification: PGC-1alpha KO vs. Wild Type
13. Effect of PGC-1alpha and PGC-1beta on gene expression in myocytes and hepatocytes ( Contact: Bruce Spiegelman)
platform: Affymetrix MG_U74A
No. of chips: 12
Specimen: Cell line (Hepatocyte for Primary Hepatocytes and muscle cell for C2C12 Myocytes)
Variables: 2 Stratum
1. Genetic modifications: over expression of Ad-GFP vs. Ad-PGC-1a vs. Ad-PGC-1b
2. Cell types: Hepatocyte for Primary Hepatocytes vs. muscle cell for C2C12 Myocytes
14. 3T3-L1 Fibroblast Cells, 3T3-L1 Adipocyte Cells, and Mouse Skeletal ( Contact: Michael Czech)
3T3-L1 Fibroblast total RNA was isolated from 3T3-L1 fibroblast cells grown in culture for 7 days to a quiescent state (day 0 of differentiation). RNA was isolated from three different days for each replicate. 3T3-L1 Adipocyte total RNA was isolated from 3T3-L1 adipocyte cells grown in culture for 7 days post addition of differentiation media. Briefly, differentiation of fibroblasts to adipocytes was induced after 7 days by incubating the cells for 3 days with high-glucose Dulbeccos modified Eagles medium (DMEM) containing 10% fetal bovine serum, 5 A,A ug of insulin per ml, 0.25 AuM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, 50 U of penicillin per ml, and 50 A,Aug of streptomycin sulfate per ml. The cells were incubated for an additional 4 days in the same medium without dexamethasone and 3-isobutyl-1-methylxanthine. RNA was isolated from three different days for each replicate. Mouse skeletal muscle tissue was harvested from 15-16wk old, male, Balb/C mice.
platform: Affymetrix MG_U74A
No. of chips: 27
Specimen: Fibroblast, Differentiated Adipocytes, Mouse Skeletal Muscle
Variables: Fibroblast vs. Differentiated Adipocytes (after 7days) vs. Mouse Skeletal Muscle
15. 3T3-L1 Adipocyte Differentiation - Time Course ( Contact: Michael Czech)
Total RNA was isolated from 3T3-L1 fibroblast cells grown in culture for 7 days to a quiescent state (Adipocyte Day 0 Differentiation). Total RNA was isolated from 3T3-L1 adipocytes at day 2, day 4 and day 6 post addition of differentiation media. Briefly, differentiation of fibroblasts to adipocytes was induced after 7 days by incubating the cells for 3 days with high-glucose Dulbecco s modified Eagle s medium (DMEM) containing 10% fetal bovine serum, 5 A ug of insulin per ml, 0.25 A uM dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, 50 U of penicillin per ml, and 50 A ug of streptomycin sulfate per ml. The cells were incubated for an additional 4 days in the same medium without dexamethasone and 3-isobutyl-1-methylxanthine. RNA was isolated from two different days for each replicate.
platform: Affymetrix MG_U74A
No. of chips: 22
Specimen: fibroblasts differentiating to adipocytes
Variables: Time series (0 day - 2 days - 4 days - 6 days)
16. Brown preadipocyte IRS knockout profiling 1 ( Contact: Ronald C Kahn)
Prediction of preadipocyte differentiation by gene expression reveals role of
insulin receptor substrates and necdin.
Tseng Yu-Hua, Butte Atul J, Kokkotou Efi, Yechoor Vijay K, Taniguchi Cullen
M, Kriauciunas Kristina M, Cypess Aaron M, Niinobe Michio, Yoshikawa Kazuaki,
Patti Mary Elizabeth, Kahn C Ronald
Nature cell biology. , 2005, 7, 6, 601-11
platform: Affymetrix MG_U74A
No. of chips: 28
Specimen: brown preadipocytes
Variables: IRS KO vs. Wild Type
17. Fat and Normal adipocytes from insulin receptor knockout mice sorted into small and large cells ( Contact: Ronald C Kahn)
Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor
knock-out mice is associated with differences in patterns of gene expression.
Bluher Matthias, Patti Mary-Elizabeth, Gesta Stephane, Kahn Barbara B, Kahn C
Ronald
The Journal of biological chemistry. , 2004, 279, 30, 31891-901
platform: Affymetrix MG_U74A
No. of chips: 18
Specimen: adipocytes
Variables: 2 stratum
1. cell types: Small Adipocyte for <75 micron diameter cells and Large Adipocyte for >75 micron diameter cells
2. genetic modifications: (Fat) Insulin Receptor Knock out (FIRKO) mice vs. IR (lox/lox) Controls
18. Mouse skeletal muscle - controls, streptozotocin diabetes and insulin treated ( Contact: Ronald C Kahn)
Coordinated patterns of gene expression for substrate and energy metabolism
in skeletal muscle of diabetic mice.
Yechoor Vijay K, Patti Mary-Elizabeth, Saccone Robert, Kahn C Ronald
Proceedings of the National Academy of Sciences of the United States of
America. , 2002, 99, 16, 10587-92
platform: Affymetrix MG_U74A
No. of chips: 9
Specimen: skeletal muscle
Variables: 2 stratum
1. Streptozotocin treatment: Mice which were made diabetic diabetic by i.p. injection of streptozotocin for 3 consecutive days (0.01 percent_weight_per_weight) were compared to Controls (0 percent_weight_per_weight).
2. insulin treatment: treatment vs. no treatment
19. Skeletal Muscle Insulin Receptor Knockout - Control, Streptozotocin Diabetic and Insulin Treated ( Contact: Ronald C Kahn)
Distinct pathways of insulin-regulated versus diabetes-regulated gene
expression: an in vivo analysis in MIRKO mice.
Yechoor Vijay K, Patti Mary-Elizabeth, Ueki Kohjiro, Laustsen Palle G,
Saccone Robert, Rauniyar Ravi, Kahn C Ronald
Proceedings of the National Academy of Sciences of the United States of
America. , 2004, 101, 47, 16525-30
platform: Affymetrix MG_U74A
No. of chips: 44
Specimen: skeletal muscle
Variables: 3 stratum
1. Genetic modifications : Muscle Insulin Receptor Knock out (MIRKO) vs. IR(Lox-Lox) Controls
2. Streptozotocin treatment: Mice which were made diabetic diabetic by i.p. injection of streptozotocin for 3 consecutive days (0.01 percent_weight_per_weight) were compared to Controls (0 percent_weight_per_weight).
3. insulin treatment: treatment vs. no treatment