- Email: [email protected]
Insulin resistance and postprandial hyperinsulinemia in nonalcoholic steatohepatitis
Nutrition.
metaholi.wz,
VISUALIZATION FORMATION
ulcoholic
liver
disease.
POST-ISCHEMIC
OF
IN LIVERS
ISOLATED
133
phaumucolog~
ISOLATED HYFERFERRITINEMIA WITH LIVER IRON OVERLOAD, AND DYSLIPIDEMIA.
RADICALS
FREE
FROM RATS CHRONICALLY
EXPOSED TO ETHANOL. AGasbarrini.
G. Addolorato.
A. De Luca. Internal
G. Vaeni.
Med
Ethanol major
Dept;
Catholic
of liver
reperfusion
a method
we aimed
to assess the effects
to visualize
in basal
condition
and
exposed
to a diet
containing
livers
were
buffer
containing
the organ The
and
overlay
measure emission, exposed
minutes
of
12 (C)
isolated
the
from
diffused the
in
CLS
was
g/d
of ethanol
controls
(S)
or from
D:5.06f2.2;
stress
allowing
formation
by livers
oxydative
liver
was
rats
treated
by
visualization
represents
with
started
a new
of tool
rate for
and 6 (C)
the
The and
the
assessment
distribution
exposed
by
organs
g/d of E?lOH photons pedicle
doses
imaging
spatial
few
60 min
rats
vascular
alcohol
after
After
and B:2.84f0.4
high
reperfusion.
60 min. from
from
rats
lschemia
progressively
emitted
A:2.99?0.41 CLS
to CLS
from
started
CLS
3 (A)
utilized
g/d).
in liver to
of
condition,
CLS it
after
greater compared
CONCLUSIONS:
determined the
value
image
obtained
particular,
placed
experiment.
was
24
Conversely,
in
After
then
Live
organ
and
were
g/d).
an oxygenated the
in livers (I2
significantly when
the
24
min.
throught
both
rats
120 min.
in basal
greater
a maximal
S:3.04+0.85;
to perifery.
of
12,
with
for 60
RESULTS:
groups;
In all groups,
progressively
images
in all groups.
all
(D)
respectively).
oxydative
of CLS
for
recorded
concentrations
and reached
however,
described,
live
production,
reperfusion
of reoxygenation
were
of CLS.
ethanol
a disappearence
and 24
with
distribution
of 02-
lucigenin
(CLS)
In this study,
Whistar
perfused
are
recentely
generation
(3, 6,
ischemia and
enhancer
emission
highest
during
(C5.16fl.8: xlOs/sec,
CLS
expression to
of reperfusion, to
superoxide
organs.
METHODS:
to warm
group
on OFR
of ethanol
Berthold)
chemiluminescence
diet
are a
however,
Our
of intact
ethanol
Italy.
(OFR)
production,
generation.
injury.
exposed
of Bologna*,
free radicals
on OFR
their
amount
FG&G
G. Gasbarrini.
University
on the surface
different
980,
the
OFR
F. Franceschi
A Roda*.
Oxygen
Studies
directly
reperfusion
isolated,
rate and spatial
determined increased
after
(LB
agent.
of a chronic
B Nardo*.
Bernardi*.
of Rome,
injury.
to measure
described
in a Luminograph
M
a pro-oxidant
by the difficulty
4 weeks,
P Pasini’.
P Pola.
University
is considered
cause
limited
M Simoncini.
E Roda’.
and
increased
system
here of
OFR
of ethanol-induced
injury.
IS ASSOCIATED LIVER STEATOSIS
M. Vigan&+, A. Vergani*, L. Parma*, I. Malosio”, A. Salvioni*, N. Carom+, V. Arosio*, G. Bovo+, C. Arosio”, A. Pipemo*. *Ist. Sci. Biomed., Div. Med. 1 and An. Pat. and Lab. Chim. Clin., Osp. S. Gerardo, Monza, Italy. OCentro Auxol. Ital., Osp. S. Luca, Milano, Italy. Iron overload is characterised by high serum ferritin (SF) and transferrin saturation (TS) levels. Infections, neoplasia, acute and chronic inflammatory disorders, hepatocellular necrosis and high alcohol intake induce SF increases not related to iron accumulation. Twenty-one patients with presenting unexplained high SF with normal TS (HFER), underwent a liver biopsy. Causes of non-specific HOER were excluded. Twenty showed increased liver iron concentration (LIC) (mean + SD, 74 p.Mol/g + 53). Data were compared with those of 19 sexand age-matched controls. HFE gene mutations (C282Y and H63D) were searched in patients and in 139 controls by PCRrestriction assay. LIC was significantly related to total iron removed, SF, ST and hemoglobin. Serum iron, TS, ST, GPT, hemoglobin, uricemia, cholesterol, and body mass index were significantly higher in patients than in controls. Eighty percent of the patients showed liver steatosis and 75% high serum cholesterol. The frequency of HFE gene mutations were similar in patients and in controls. Both weight reduction and iron depletion therapy respectively performed in 8 patients, induced a significant decrease of SF and ST. Our results suggest that HFER is related to both liver iron overload, liver steatosis and dyslipidemia. The underlying pathogenetic mechanisms of this clinical pattern is still to be defined. The role of HFE gene mutations seems less important.
1 P/CO8/020 1 INSULIN RESISTANCE ANDPOSTPRANDIAL HYPERINSULINEMIAIN NONALCOHOLICSTEATOHEPATITIS E. Tankmt. S. BiberoElu. Z. Hekimsov. E. Ellidokuz, A. KtioelioElu. Gastroenterology, Endocrinology and Pathology Depts. Dokuz Eyliil University Hospital, izmir, Turkey. Nonalcoholic steatohepatitis (NASH) is an increasingly diagnosed clinicopathological entity characterized by fatty liver with lobular hepatitis and absence of alcohol consumption. In this study we investigated the blood glucose, insulin and c-peptide levels of NASH patients during oral glucose tolerance test (OG’lT) and compared with age and gender matched normal (liver function tests and ultrasound) individuals. Sixteen patients who were diagnosed as NASH between 1992 and 1996 were included in the study. The diagnosis of NASH were based upon i) definitely no alcohol consumption, ii) presence of diffuse steatosis in the liver with lobular inllammation and hepatocyte degeneration. Spotty necrosis were present in most patients while mild to moderate fibrosis were detected in 6 patients and Mallory bodies in 2 patients. Results: According to OGTT, there were one diabetic and one impaired glucose tolerance among patients while it was totally normal in the control group. The results are shown in table. Control Case P WHR (Waist-hip ratio) [email protected] o.91jzoH).07 0.037 Insulin 0 29.3i26.4 27.3G.8 0.213 Insulin 120 53.5*34.4 119.W79.9 0.002 A significant difference was found in the mean second hour insulin levels between case and control groups. The difference in mean insulin-glucose ratio at 120 minutes was also sign&ant (0.92 vs 0.52 respectively in case and control groups, ~0.01). Odds ratio for 120 minute insulin level in NASH was 9 (1.23-82.83, CI 95%). Conclusion: Postprandial hypezinsuhnemia and insulin resistance which is also associated by abdominal obesity (increased WHR) is a distinct feature of NASH. These results also suggest that NASH share the same metabolic disturbances with isolated steatosis of the liver.
HEPATIC GLYCOGEN METABOLISM IN RATS WITH BILIARY CIRRHOSIS AFTER Y-EN-ROUX ANASTOMOSIS L. Kr&enbiihl&, B. Hanenbuch’. M. Scbfer’. S. Kr&benbiihl*. Depts. of *Clinical Pharmacology and &Visceral Surgery, Univ. of Beme, and ‘Clinical Pharmacology, Univ. of Zurich, Switzerland Background: Rats with long-term bile duct ligation (BDL) have a reduced hepatic glycogen content and impaired activities of glycogen synthase (GS) and phosphorylase (GP). Aims: To study the reversibility of these changes by Y-en-Roux anastomosis CyR) on the functional and molecular level. Methods: Rats were pair-fed and studied in the fed state. BDL (n=6) or sham-operation (CON, n=6) for 4 w. Reversal of BDL by YR for 5 (YR5, s8) or 14 d (YR14, s6). Glycogen, enzyme activities and Northern blots by routine methods (Hepatology 1996;24:902). Results: Treated rats and CON did not differ in body weight. Serum bilirubin, bile acids and liver weight normalized within 14 d after YR. Activities of GP and GS were decreased in BDL by 58% and 55%, respectively, in YR5 by 33% and 52%, respectively and had recovered in YR14. Liver glycogen (mg/g) and expression of glycogenin, GS and GP (all relative units) are given in the Table (mean&& *p
~
Conclusions: Hepatic glycogen content, enzyme activities and glycogenin normalize quickly after YR, whereas expression of GS and GP recover more slowly or not. Normalized activities of GP despite reduced expression suggest increased protein stability, more efficient translation, and/or alterations in regulation.
metaholi.wz,
VISUALIZATION FORMATION
ulcoholic
liver
disease.
POST-ISCHEMIC
OF
IN LIVERS
ISOLATED
133
phaumucolog~
ISOLATED HYFERFERRITINEMIA WITH LIVER IRON OVERLOAD, AND DYSLIPIDEMIA.
RADICALS
FREE
FROM RATS CHRONICALLY
EXPOSED TO ETHANOL. AGasbarrini.
G. Addolorato.
A. De Luca. Internal
G. Vaeni.
Med
Ethanol major
Dept;
Catholic
of liver
reperfusion
a method
we aimed
to assess the effects
to visualize
in basal
condition
and
exposed
to a diet
containing
livers
were
buffer
containing
the organ The
and
overlay
measure emission, exposed
minutes
of
12 (C)
isolated
the
from
diffused the
in
CLS
was
g/d
of ethanol
controls
(S)
or from
D:5.06f2.2;
stress
allowing
formation
by livers
oxydative
liver
was
rats
treated
by
visualization
represents
with
started
a new
of tool
rate for
and 6 (C)
the
The and
the
assessment
distribution
exposed
by
organs
g/d of E?lOH photons pedicle
doses
imaging
spatial
few
60 min
rats
vascular
alcohol
after
After
and B:2.84f0.4
high
reperfusion.
60 min. from
from
rats
lschemia
progressively
emitted
A:2.99?0.41 CLS
to CLS
from
started
CLS
3 (A)
utilized
g/d).
in liver to
of
condition,
CLS it
after
greater compared
CONCLUSIONS:
determined the
value
image
obtained
particular,
placed
experiment.
was
24
Conversely,
in
After
then
Live
organ
and
were
g/d).
an oxygenated the
in livers (I2
significantly when
the
24
min.
throught
both
rats
120 min.
in basal
greater
a maximal
S:3.04+0.85;
to perifery.
of
12,
with
for 60
RESULTS:
groups;
In all groups,
progressively
images
in all groups.
all
(D)
respectively).
oxydative
of CLS
for
recorded
concentrations
and reached
however,
described,
live
production,
reperfusion
of reoxygenation
were
of CLS.
ethanol
a disappearence
and 24
with
distribution
of 02-
lucigenin
(CLS)
In this study,
Whistar
perfused
are
recentely
generation
(3, 6,
ischemia and
enhancer
emission
highest
during
(C5.16fl.8: xlOs/sec,
CLS
expression to
of reperfusion, to
superoxide
organs.
METHODS:
to warm
group
on OFR
of ethanol
Berthold)
chemiluminescence
diet
are a
however,
Our
of intact
ethanol
Italy.
(OFR)
production,
generation.
injury.
exposed
of Bologna*,
free radicals
on OFR
their
amount
FG&G
G. Gasbarrini.
University
on the surface
different
980,
the
OFR
F. Franceschi
A Roda*.
Oxygen
Studies
directly
reperfusion
isolated,
rate and spatial
determined increased
after
(LB
agent.
of a chronic
B Nardo*.
Bernardi*.
of Rome,
injury.
to measure
described
in a Luminograph
M
a pro-oxidant
by the difficulty
4 weeks,
P Pasini’.
P Pola.
University
is considered
cause
limited
M Simoncini.
E Roda’.
and
increased
system
here of
OFR
of ethanol-induced
injury.
IS ASSOCIATED LIVER STEATOSIS
M. Vigan&+, A. Vergani*, L. Parma*, I. Malosio”, A. Salvioni*, N. Carom+, V. Arosio*, G. Bovo+, C. Arosio”, A. Pipemo*. *Ist. Sci. Biomed., Div. Med. 1 and An. Pat. and Lab. Chim. Clin., Osp. S. Gerardo, Monza, Italy. OCentro Auxol. Ital., Osp. S. Luca, Milano, Italy. Iron overload is characterised by high serum ferritin (SF) and transferrin saturation (TS) levels. Infections, neoplasia, acute and chronic inflammatory disorders, hepatocellular necrosis and high alcohol intake induce SF increases not related to iron accumulation. Twenty-one patients with presenting unexplained high SF with normal TS (HFER), underwent a liver biopsy. Causes of non-specific HOER were excluded. Twenty showed increased liver iron concentration (LIC) (mean + SD, 74 p.Mol/g + 53). Data were compared with those of 19 sexand age-matched controls. HFE gene mutations (C282Y and H63D) were searched in patients and in 139 controls by PCRrestriction assay. LIC was significantly related to total iron removed, SF, ST and hemoglobin. Serum iron, TS, ST, GPT, hemoglobin, uricemia, cholesterol, and body mass index were significantly higher in patients than in controls. Eighty percent of the patients showed liver steatosis and 75% high serum cholesterol. The frequency of HFE gene mutations were similar in patients and in controls. Both weight reduction and iron depletion therapy respectively performed in 8 patients, induced a significant decrease of SF and ST. Our results suggest that HFER is related to both liver iron overload, liver steatosis and dyslipidemia. The underlying pathogenetic mechanisms of this clinical pattern is still to be defined. The role of HFE gene mutations seems less important.
1 P/CO8/020 1 INSULIN RESISTANCE ANDPOSTPRANDIAL HYPERINSULINEMIAIN NONALCOHOLICSTEATOHEPATITIS E. Tankmt. S. BiberoElu. Z. Hekimsov. E. Ellidokuz, A. KtioelioElu. Gastroenterology, Endocrinology and Pathology Depts. Dokuz Eyliil University Hospital, izmir, Turkey. Nonalcoholic steatohepatitis (NASH) is an increasingly diagnosed clinicopathological entity characterized by fatty liver with lobular hepatitis and absence of alcohol consumption. In this study we investigated the blood glucose, insulin and c-peptide levels of NASH patients during oral glucose tolerance test (OG’lT) and compared with age and gender matched normal (liver function tests and ultrasound) individuals. Sixteen patients who were diagnosed as NASH between 1992 and 1996 were included in the study. The diagnosis of NASH were based upon i) definitely no alcohol consumption, ii) presence of diffuse steatosis in the liver with lobular inllammation and hepatocyte degeneration. Spotty necrosis were present in most patients while mild to moderate fibrosis were detected in 6 patients and Mallory bodies in 2 patients. Results: According to OGTT, there were one diabetic and one impaired glucose tolerance among patients while it was totally normal in the control group. The results are shown in table. Control Case P WHR (Waist-hip ratio) [email protected] o.91jzoH).07 0.037 Insulin 0 29.3i26.4 27.3G.8 0.213 Insulin 120 53.5*34.4 119.W79.9 0.002 A significant difference was found in the mean second hour insulin levels between case and control groups. The difference in mean insulin-glucose ratio at 120 minutes was also sign&ant (0.92 vs 0.52 respectively in case and control groups, ~0.01). Odds ratio for 120 minute insulin level in NASH was 9 (1.23-82.83, CI 95%). Conclusion: Postprandial hypezinsuhnemia and insulin resistance which is also associated by abdominal obesity (increased WHR) is a distinct feature of NASH. These results also suggest that NASH share the same metabolic disturbances with isolated steatosis of the liver.
HEPATIC GLYCOGEN METABOLISM IN RATS WITH BILIARY CIRRHOSIS AFTER Y-EN-ROUX ANASTOMOSIS L. Kr&enbiihl&, B. Hanenbuch’. M. Scbfer’. S. Kr&benbiihl*. Depts. of *Clinical Pharmacology and &Visceral Surgery, Univ. of Beme, and ‘Clinical Pharmacology, Univ. of Zurich, Switzerland Background: Rats with long-term bile duct ligation (BDL) have a reduced hepatic glycogen content and impaired activities of glycogen synthase (GS) and phosphorylase (GP). Aims: To study the reversibility of these changes by Y-en-Roux anastomosis CyR) on the functional and molecular level. Methods: Rats were pair-fed and studied in the fed state. BDL (n=6) or sham-operation (CON, n=6) for 4 w. Reversal of BDL by YR for 5 (YR5, s8) or 14 d (YR14, s6). Glycogen, enzyme activities and Northern blots by routine methods (Hepatology 1996;24:902). Results: Treated rats and CON did not differ in body weight. Serum bilirubin, bile acids and liver weight normalized within 14 d after YR. Activities of GP and GS were decreased in BDL by 58% and 55%, respectively, in YR5 by 33% and 52%, respectively and had recovered in YR14. Liver glycogen (mg/g) and expression of glycogenin, GS and GP (all relative units) are given in the Table (mean&& *p
~
Conclusions: Hepatic glycogen content, enzyme activities and glycogenin normalize quickly after YR, whereas expression of GS and GP recover more slowly or not. Normalized activities of GP despite reduced expression suggest increased protein stability, more efficient translation, and/or alterations in regulation.