Last flight from JFK

Higher glycogen level in PERK KO neonates

Hepatic microsomal glucose-6-phosphatase system and SIDS

Microassay techniques and monospecific antibodies were used to study the hepatic glucose-6-phosphatase system in liver samples from 55 infants who had died suddenly and unexpectedly, including 38/55 victims of sudden infant death syndrome (SIDS). Raised hepatic glycogen was found in 10/38, all of whom had a diagnosis of SIDS,

Of the 10 infants with raised hepatic glycogen who had a diagnosis of SIDS, 8/10 had glucose-6-phosphatase deficiency (type 1a glycogen storage disease), and 2/10 had transport protein T2 deficiency (type 1c glycogen storage disease).

Burchell A, et al, Lancet. 1989;2:291-4.

Phenotype of GSD-1a mice

severe hypoglycemia,

growth retardation,

perinatal lethality,

deformity of joints,

hepatomegaly,

kidney enlargement,

hyperlipidemia.Lei KJ et al,Nat Genet. 1996;13:203-9.

G6-Pase systems

Catalytic subunit inside ER

Transporter subunits transport G6-P into ER

First test (Add Triton X100)

Glucose-6-phosphatase activity

0

1

2

3

4

5

6

0 2 4 6 8 10 12

G6P concentration(mM)

V (

pro

du

ctio

n o

f p

)

A B

C D

KO1

KO2

WT2

WT1

Second Test(Without Triton X100)

G6-Pase w ithout TritonX100

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0 2 4 6 8 10 12

Substrate concentration

V (

P p

rod

uct

ion

)

A

B

C

D

WT1

WT2

KO1

KO2

Second test-With TritonX100

G6-Pase w ith tritonX100

0

0.5

1

1.5

2

2.5

3

3.5

0 2 4 6 8 10 12

Substrate concentration

V (

P p

rod

uct

ion

)

A

B

C

D

WT1

WT2&KO2

KO1

Not reliable ?

Increased insulin sensitivity