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Effect of ambrein on blood glucose levels of rats
Journal of Ethnopharmacology. Elsevier Scientific
Publishers
35 ( I99 Ireland
1) 145- 148
145
Ltd.
Effect of ambrein
on blood glucose levels of rats S.A. Taha
Ambrein
reduced the blood glucose level of normal and moderately
of severely-diabetic the hyperglycemia
rats. Ambrein
of glucose-loaded
brein may be mediated
Key work
did not reduce the hyperglycemia
alloxan-diabetic of glucose-loaded
rats in the absence of mannoheptulose.
ambrein;
diabetic
mg/kg to three groups (n/group = 5) of overnightfasted albino Wistar male rats (body weight range 180-250 g) by gastric intubation (0.1 ml/animal). A fourth group received olive oil only (0.1 ml/animal) and acted as a control group. Blood glucose levels were determined immediately prior to dosing and +1.5, +3, +4.5. +6, +I4 and +24 h after dosing. Blood was sampled from a tail vein. Blood samples were estimated in duplicate by an enzymatic calorimetric assay procedure, using an Unicam SP600 (series 2) spectrophotometer at a wavelength of 450 nm and the reading converted into glucose concentration (mg/lOO ml whole blood).
is a major constituent of ambergris, an secretion of the sperm blue whale (Pysrter cudon). The authentication, isolation, identification and clinical uses (folklore medicine) of ambrein and ambergris have been described elsewhere (Taha, 1989a,b; Taha and Rashid. 1990). The present study attempts to define the effects of ambrein on blood glucose levels in the rat. Ambrein
internal
Materials and Methods
Ambrein was isolated and identified chemically by the author from ambergris purchased from a local market in Riyadh, Saudi Arabia. Alloxan monohydrate and mannoheptulose were purchased from Sigma Chemical Co. (St. Louis, MO). Ambrein was dissolved in olive oil and the other drugs were dissolved in distilled water.
Alhuun
Cb,,c,,~/~o,7(/(,77~,(, 70; S.A. Taha.
Department
of Pharmacology.
King Saud University.
P.O. Box 2457.
1451. Saudi Arabia
0
1991 Elsevier Scientific
Published and Printed in Ireland
Publishers Ireland
u’iuhetic studiirs
Four groups of albino Wistar male rats, 5 rats/group (body weight range: 180-200 g) were injected subcutaneously with 25 or 45 mg/kg alloxan monohydrate on three successive days. On the ninth day after the initial dosing, the urine of each rat was tested with Clinistix strips (Ames) to indicate the severity of its diabetic state. The two groups which received 25 mg/kg alloxan monohydrate showed moderate diabetes (191-195/mg/lOO ml blood), while the other two groups which received 45 mg/kg alloxan monohydrate showed severe diabetes (575-590 mg/lOO ml blood). The rats were fasted for 18 h
Various amounts of ambrein were dissolved in olive oil and administered at doses of 1, 5 or 10
0378-8741/$03.50
but it reduced
animals
Introduction
Riyadh-I
rats also given mannoheptulose
Rcsultx suggested that the hypoglycemic activity of am-
by enhanced glucose utilization.
hypoglycemia;
College of Pharmacy.
rats but did not reduce the blood glucose levels
Ltd.
146
hypoglycemia at each effective dose level (5 mg and IO mgikg) occurred + I4 h after oral administration and began to return to control levels at +24 h.
and their blood glucose levels were determined as described above. Each group of rats then received 5 mgikg of ambrein dissolved in olive oil by gastric intubation (0.1 ml/animal). Blood glucose concentrations were determined +3, +6 and +I2 h after dosing.
A Ilo.wn
Four groups of five overnight-fasted, albino Wistar rats (body weight range: 170-200 g) were used. Blood levels were determined in all animals prior to dosing. Two groups were administered ambrein 5 mg/kg (dissolved in olive oil) by gastric intubation (0.1 ml/animal) while another two groups received only olive oil (0.1 ml/animal) by the same route (controls). Two hours later, one of the ambrein groups and one of the control groups were injected subcutaneously with 50 mgikg mannoheptulose while the other two groups received normal saline (0.1 ml/animal). All four groups were then immediately injected subcutaneously with a glucose load of 2.0 g/kg. Blood glucose levels were determined at appropriate intervals over the following 4-h period.
Mean blood glucose levels induced by the glucose loading of control animals reached a level of 190 + 21 and 224 + I8 mg/lOO ml blood at 30 and 60 min after loading (Fig. I). In the presence of mannoheptulose, this was elevated to 295 + I9 and 345 f I2 mg/IOO ml blood at 30 and 60 min. In/ ambrein-treated animals, glucose levels fell from 70 f 4 and 80 f 5 mg/lOO ml blood to 50 f 4 and 60 + 5 mg/lOO blood, respectively, just before glucose loading. In the absence of man-
Results Mormul
ruts
studies
Blood glucose concentrations were significantly reduced by ambrein (Table I ). Maximum
TABLE
I
EFFECT OF THREE ADMINISTRATION
ORAL
The control
group
Dose
Blood glucose
(mgikg) Control
I
dirr hr t ic s t udics
The results are presented in Table 2. The two groups of rats that received 45 mgikg of alloxan showed initial mean blood glucose levels of 575 and 590 mg/lOO ml blood, indicating a severe diabetic state. The moderately diabetic animals that received 25 mgikg of alloxan showed mean initial blood glucose levels of I95 and I9 I mg/ IO0 ml blood. In these animals, ambrein caused a significant reduction in blood glucose level of 37% at -t-6 h. The severely diabetic animals treated with ambrein did not show any significant reduction in blood glucose levels.
received
0 84.0 f (100) 81.2 f 82.4 f
IO
(100) 75.2 f
olive oil (0.1 ml/animal)
2.8
83.8 f
2.4
(100) 71.2 f
1.6
69.4 f
3.4
(84) 60.1 f
“Figures in parentheses Statistically significant
only.
BLOOD
GLUCOSE
Each value is the mean
+3 h
f
LEVELS OF RATS FOLLOWING
S.E.M.
ORAL
of 5 animals.
(80)
82.2 f
5.6
(98) 72.6 f
2.1:
(89) 55.5 zt 2.9***
(87) 53.5 f
4.6*
(68) 52.2 f
(65) 51.0 f
(71)
+6 h
+I4 h
4
80.1 f 4.2
75.2
4.6
(95) 70.3 zt 3.6
(89) 68.2 f
2.9***
(86.5) 51.0 f
3.l**
(62) 44.2 + 2.5***
(841 49.0 f (59.5) 42.4 f
(59)
(56)
+4.5 h
3.8
(88)
(100)
ON MEAN
levels (mg/lOO ml)” +I.5 h
(100) 5
DOSES OF AMBREIN
3.0
80.9 f
4.7
(95) 70.5 f
3.3***
(68)
1.6***
represent glucose levels as a percentage of the initial level (0 time). from the control: *P < 0.05. **P < 0.01, ***P < 0.001.
l
+24 h 3.7
71.6 f
2.0
3.7
(85) 74.8 f
3
6.5** 3.1**
(92) 68.0 f (82.5) 60.1 f (80)
6.8 4.0*
147
TABLE
2
EFFECT
OF AMBREIN
The control
groups
IN ALLOXAN-DIABETIC
received
Diabetic state
olive oil (0.
Treatment (mg/kg)
Moderately diabetic
195 f
Ambrein
aFigures in parentheses Statistically significant
I2 I2
Ambrein
(100) 590 f 21 (100) 575 f 33
(5)
(loo)
ADMINISTRATION. =t S.E.M.
of 5 animals.
+6 h
+3 h
represent glucose levels as a percentage from the respective control: *P < 0.05,
194 LIZ8
I91 f
(99) 142 f l4* (74.5) 590 l I7
(98) I20 f
(100) 565 f
(100) 561 f (97.5)
21
(98)
(63) 593 f
+I2 h 9
179 f
II
9***
(92) 138 f
8**
I7
(72) 591 f
26
21
(100) 478 l 52 (83)
of the initial level (0 time).
**P < 0.01. ***P< 0.001.
400
noheptulose, levels rose to I IO f 5 mg/lOO ml blood before falling towards original levels (Fig. 1). However, in the presence of mannoheptulose, the glucose levels of ambrein-treated glucose loaded animals rose to 270 f 13 and 312 f 18 mg/lOO ml blood at 30 and 60 min, respectively. Therefore, it appears that the controlling influence of ambrein on the blood glucose levels following the administration of a glucose load is abolished in the presence of mannoheptulose.
300
6
Discussion
g It is well known that alloxan will destroy the beta-cells of pancreas and induce hyperglycemia (Dunn et al., 1943; Goldner and Gomori, 1943; Lazarus et al., 1958; Owerbach et al., 1982;
Fig. I. Effect of ambrein (5 mg/kg; A , A ) on levels when a glucose load (2 g/kg) is injected 2 h after oral administration of ambrein. in the symbols) or absence (open symbols) of 50 mgikg
rat blood glucose subcutaneously presence (closed mannoheptulose.
Control animals ( 0 , 0 ) received olive oil orally instead of ambrein. Each value is the mean result from 5 animals. Statistically significant from control: *P < 0.05. **P< 0.01. ***P< 0.001. Control + glucose ( 0 ) was further used as control for control + mannoheptulose
ORAL
levels (mg/lOO ml)”
0
(100) I91 f
FOLLOWING
only. Each value is the mean
Blood glucose
Control
(5) Control
Severely diabetic
I ml/animal)
RATS
+ glucose
( 0 ).
200
Z
3 S 3
+ Loading ;
2j9
5
Time(h)
i
s
ii
148
Joseph, 1985). Mannoheptulose is an inhibitor of glucose phosphorylation and glucose-stimulated insulin secretion (Henquin et al., 1986; Zawalich et al., 1986; Aprille et al., 1987; Choy et al., 1987; Grill et al., 1987; Grimaldi, 1987; Zawalich et al., 1987; Guest et al., 1989a,b). The present experiments demonstrate that ambrein can reduce the blood glucose of rats. These effects were only produced in non-diabetic rats, moderate alloxan-diabetic rats and glucose-loaded rats. In contrast, ambrein did not reduce the blood glucose levels of severely diabetic rats or in the presence of mannoheptulose. In the light of these findings, the mechanism by which ambrein lowers the blood glucose level of rats may be due to an effect on glucose-stimulated insulin release from beta-cells, since the hypoglycemic effect of ambrein is not changed in the presence of glucose injection, but is abolished in the presence of mannoheptulose and severe beta-cell destruction. However, further study is necessary to reveal the exact mechanism of the hypoglycemic activity of ambrein.
Grill. V.. Westberg, M. and Ostcnson. C. (19X7) Beta ccl1 insensitivity
Grimaldi.
rapidly
Siddle,
of the biosynthesis Coordinate
translational
all, granule
R.T.
and Nosek,
acute alteration
M.T.
(1987)
G..
Brennan.
W.A..
Mitochondrial
Kelley.
function
of the endogenous insulin-to-glucagon
Biochen~ic*rr/ md
after
matrix
constituents.
Joco-rd
isolated
J.C..
(1(3X6)
mannoheptulose Dunn.
J.. Sheehan,
treated mice. Ctrr~c~ Lrfrc,r.s 37. 33-39. H. and Maletchic.
islets of Langerhans
produced
N. (lY43)
experimentally.
Necrosis of Ltr~c,c,r I.
M. and Gomori.
G. (IY43)
Enclr~c~rif~ol~~.~l~ 33. 2Y7-29Y.
Alloxan-induced
diabetes.
proteins.
Bioc~lrtvrrid
Jw~1711/ 757.
ofcarboxypcptidasc
rat islets of Langerhans.
Nenquin.
Magnesium
M..
Awouters,
uptake
Eio-0pcwrr Jo1ot7trl Joseph,
L.
(19X5)
Glycogen. F.
of‘
H and inBioc~hc~~~/~~o/
by
P. and Cogncau.
pancreatic
islet
M.
cells
is
Bioc~lrc,t71;.\~1.1~ 17. 653-657.
Insulin
an d
In: A.G. Gilman,
Murad
(Eds.).
mtrcoh,~icvrl
hypoglycemic
Goorl777trrr trml
Publishing Co.. New York. Lazarus.
oral
L.S. Goodman.
S.. Sydney,
morphologic
T.W.
Gihm
Btrsi.s c!f Tllc,rtr/,c,7r/ic,.\. 7th
k
drugs. Rail and
Tlrc
Edn..
P/w-
Macmillan
pp. l4Y3-1512.
S. and Yolk.
B. (195X)
Functional
and
studies on the effects of Orinase on the pan-
creas. ~77tk,c,~i77o/t~~~,~, 63. 292-307. D..
Billeshollc.
S. and Ncrup.
DNA
%ha.
S.
P..
Schroll.
J. (lY82)
sequences
atherosclerosis.
Taha.
( IYXYa)
S. and Rashid.
M..
the
insulin
gene
pharmacological
and
investigation
screening
of the Internal
Diaz,
ol
secre-
PtrX-istc~r ./o~r/~tr/ of Plrtrr-
I OS-I IO.
S. (IYYO) The effect of amhrcin
system.
W.S..
K.. hct-
flanking
General
S. ( IYXYh) Chemical
diovascular
Johansen
Possible association
Lcrr7cx~/2. I29 I - 139.7.
on car-
fckisrrr~r Jorwi7cil of P/rl77.777trc,r,/f,,~ I. 7. V. and Cole.
on insulin secretion
S. (19X6)
lnflucnce
ol
from
iholatcd rat islets.
Jour77rrlo/‘Plrc1r17rcrc,olr1,~~~ m7(/ E.vprimcw/trl
Tltc,r,rrl,c,rrric..\ 217.
826475,. Zawalish. G.F.
W.S.. (1987)
Rasmussen. G.. Tumun, Influence
linoglirids (McN-3935) islets of Langerhnns.
4X4-487. Goldner,
Regulation
mediated by stimulators and inhibitors of the P-cell function.
45-4X.
shock and tumor necrosis factor release in
J.C. ( IYXYa)
764. 503-50X.
Henquin.
mchendazole
(19X7) Endotoxin
Con-
control is cxcrted on some, but not
ton. J.C. (lY8Yb) Co-secretion sulin from
Zawalich.
Choy, Y.. Cheng. C., Luey. I.. Loh. S.. Fung. K. and Lee. C.
Biosyn-
protein.
Guest, P.C., Pipeleers. D.. Rossier. J.. Rhodes. C.J. and Hut-
142.
315-321.
J.C. (19X7)
43 I-437.
ratio.
Bioph~~sic~trl Revcwrc~lr Ci)rrrtllr,/ric,trriorls
previous
of insulin-secretory-granule
tion of the sperm blue whale. Rohweder-Dunn.
of
Jorrr~7rrl 245. 567-573.
Guest. P.C.. Rhodes. C.J. and Hutton.
,77lrc?7r/icul .%%wc~c’.s 2. J.R.,
effect
K. and Hutton,
trol by glucose. Biadwrnicd
-ha.
Aprille,
reversible
Jotrr-nrrlo/ C/;rrictrl /~~res/i,gtr/ior~X0. 644~66Y.
K.A..
ween
References
a
thesis of insulin secretory granule membrane
Paulsen,
This study was supported by Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
for
hyperglycemia.
Owerhach.
Acknowledgement
diabetes.
in a rat model of non-insulin-dependent
Evidence
of
the
oral
R.W.
and Tutwilel-.
hypoglycemic
agent
on insulin secretion from isolated 711 D7tk,c,ii,7ok?~,
120. HXO-XXZ.
Publishers
35 ( I99 Ireland
1) 145- 148
145
Ltd.
Effect of ambrein
on blood glucose levels of rats S.A. Taha
Ambrein
reduced the blood glucose level of normal and moderately
of severely-diabetic the hyperglycemia
rats. Ambrein
of glucose-loaded
brein may be mediated
Key work
did not reduce the hyperglycemia
alloxan-diabetic of glucose-loaded
rats in the absence of mannoheptulose.
ambrein;
diabetic
mg/kg to three groups (n/group = 5) of overnightfasted albino Wistar male rats (body weight range 180-250 g) by gastric intubation (0.1 ml/animal). A fourth group received olive oil only (0.1 ml/animal) and acted as a control group. Blood glucose levels were determined immediately prior to dosing and +1.5, +3, +4.5. +6, +I4 and +24 h after dosing. Blood was sampled from a tail vein. Blood samples were estimated in duplicate by an enzymatic calorimetric assay procedure, using an Unicam SP600 (series 2) spectrophotometer at a wavelength of 450 nm and the reading converted into glucose concentration (mg/lOO ml whole blood).
is a major constituent of ambergris, an secretion of the sperm blue whale (Pysrter cudon). The authentication, isolation, identification and clinical uses (folklore medicine) of ambrein and ambergris have been described elsewhere (Taha, 1989a,b; Taha and Rashid. 1990). The present study attempts to define the effects of ambrein on blood glucose levels in the rat. Ambrein
internal
Materials and Methods
Ambrein was isolated and identified chemically by the author from ambergris purchased from a local market in Riyadh, Saudi Arabia. Alloxan monohydrate and mannoheptulose were purchased from Sigma Chemical Co. (St. Louis, MO). Ambrein was dissolved in olive oil and the other drugs were dissolved in distilled water.
Alhuun
Cb,,c,,~/~o,7(/(,77~,(, 70; S.A. Taha.
Department
of Pharmacology.
King Saud University.
P.O. Box 2457.
1451. Saudi Arabia
0
1991 Elsevier Scientific
Published and Printed in Ireland
Publishers Ireland
u’iuhetic studiirs
Four groups of albino Wistar male rats, 5 rats/group (body weight range: 180-200 g) were injected subcutaneously with 25 or 45 mg/kg alloxan monohydrate on three successive days. On the ninth day after the initial dosing, the urine of each rat was tested with Clinistix strips (Ames) to indicate the severity of its diabetic state. The two groups which received 25 mg/kg alloxan monohydrate showed moderate diabetes (191-195/mg/lOO ml blood), while the other two groups which received 45 mg/kg alloxan monohydrate showed severe diabetes (575-590 mg/lOO ml blood). The rats were fasted for 18 h
Various amounts of ambrein were dissolved in olive oil and administered at doses of 1, 5 or 10
0378-8741/$03.50
but it reduced
animals
Introduction
Riyadh-I
rats also given mannoheptulose
Rcsultx suggested that the hypoglycemic activity of am-
by enhanced glucose utilization.
hypoglycemia;
College of Pharmacy.
rats but did not reduce the blood glucose levels
Ltd.
146
hypoglycemia at each effective dose level (5 mg and IO mgikg) occurred + I4 h after oral administration and began to return to control levels at +24 h.
and their blood glucose levels were determined as described above. Each group of rats then received 5 mgikg of ambrein dissolved in olive oil by gastric intubation (0.1 ml/animal). Blood glucose concentrations were determined +3, +6 and +I2 h after dosing.
A Ilo.wn
Four groups of five overnight-fasted, albino Wistar rats (body weight range: 170-200 g) were used. Blood levels were determined in all animals prior to dosing. Two groups were administered ambrein 5 mg/kg (dissolved in olive oil) by gastric intubation (0.1 ml/animal) while another two groups received only olive oil (0.1 ml/animal) by the same route (controls). Two hours later, one of the ambrein groups and one of the control groups were injected subcutaneously with 50 mgikg mannoheptulose while the other two groups received normal saline (0.1 ml/animal). All four groups were then immediately injected subcutaneously with a glucose load of 2.0 g/kg. Blood glucose levels were determined at appropriate intervals over the following 4-h period.
Mean blood glucose levels induced by the glucose loading of control animals reached a level of 190 + 21 and 224 + I8 mg/lOO ml blood at 30 and 60 min after loading (Fig. I). In the presence of mannoheptulose, this was elevated to 295 + I9 and 345 f I2 mg/IOO ml blood at 30 and 60 min. In/ ambrein-treated animals, glucose levels fell from 70 f 4 and 80 f 5 mg/lOO ml blood to 50 f 4 and 60 + 5 mg/lOO blood, respectively, just before glucose loading. In the absence of man-
Results Mormul
ruts
studies
Blood glucose concentrations were significantly reduced by ambrein (Table I ). Maximum
TABLE
I
EFFECT OF THREE ADMINISTRATION
ORAL
The control
group
Dose
Blood glucose
(mgikg) Control
I
dirr hr t ic s t udics
The results are presented in Table 2. The two groups of rats that received 45 mgikg of alloxan showed initial mean blood glucose levels of 575 and 590 mg/lOO ml blood, indicating a severe diabetic state. The moderately diabetic animals that received 25 mgikg of alloxan showed mean initial blood glucose levels of I95 and I9 I mg/ IO0 ml blood. In these animals, ambrein caused a significant reduction in blood glucose level of 37% at -t-6 h. The severely diabetic animals treated with ambrein did not show any significant reduction in blood glucose levels.
received
0 84.0 f (100) 81.2 f 82.4 f
IO
(100) 75.2 f
olive oil (0.1 ml/animal)
2.8
83.8 f
2.4
(100) 71.2 f
1.6
69.4 f
3.4
(84) 60.1 f
“Figures in parentheses Statistically significant
only.
BLOOD
GLUCOSE
Each value is the mean
+3 h
f
LEVELS OF RATS FOLLOWING
S.E.M.
ORAL
of 5 animals.
(80)
82.2 f
5.6
(98) 72.6 f
2.1:
(89) 55.5 zt 2.9***
(87) 53.5 f
4.6*
(68) 52.2 f
(65) 51.0 f
(71)
+6 h
+I4 h
4
80.1 f 4.2
75.2
4.6
(95) 70.3 zt 3.6
(89) 68.2 f
2.9***
(86.5) 51.0 f
3.l**
(62) 44.2 + 2.5***
(841 49.0 f (59.5) 42.4 f
(59)
(56)
+4.5 h
3.8
(88)
(100)
ON MEAN
levels (mg/lOO ml)” +I.5 h
(100) 5
DOSES OF AMBREIN
3.0
80.9 f
4.7
(95) 70.5 f
3.3***
(68)
1.6***
represent glucose levels as a percentage of the initial level (0 time). from the control: *P < 0.05. **P < 0.01, ***P < 0.001.
l
+24 h 3.7
71.6 f
2.0
3.7
(85) 74.8 f
3
6.5** 3.1**
(92) 68.0 f (82.5) 60.1 f (80)
6.8 4.0*
147
TABLE
2
EFFECT
OF AMBREIN
The control
groups
IN ALLOXAN-DIABETIC
received
Diabetic state
olive oil (0.
Treatment (mg/kg)
Moderately diabetic
195 f
Ambrein
aFigures in parentheses Statistically significant
I2 I2
Ambrein
(100) 590 f 21 (100) 575 f 33
(5)
(loo)
ADMINISTRATION. =t S.E.M.
of 5 animals.
+6 h
+3 h
represent glucose levels as a percentage from the respective control: *P < 0.05,
194 LIZ8
I91 f
(99) 142 f l4* (74.5) 590 l I7
(98) I20 f
(100) 565 f
(100) 561 f (97.5)
21
(98)
(63) 593 f
+I2 h 9
179 f
II
9***
(92) 138 f
8**
I7
(72) 591 f
26
21
(100) 478 l 52 (83)
of the initial level (0 time).
**P < 0.01. ***P< 0.001.
400
noheptulose, levels rose to I IO f 5 mg/lOO ml blood before falling towards original levels (Fig. 1). However, in the presence of mannoheptulose, the glucose levels of ambrein-treated glucose loaded animals rose to 270 f 13 and 312 f 18 mg/lOO ml blood at 30 and 60 min, respectively. Therefore, it appears that the controlling influence of ambrein on the blood glucose levels following the administration of a glucose load is abolished in the presence of mannoheptulose.
300
6
Discussion
g It is well known that alloxan will destroy the beta-cells of pancreas and induce hyperglycemia (Dunn et al., 1943; Goldner and Gomori, 1943; Lazarus et al., 1958; Owerbach et al., 1982;
Fig. I. Effect of ambrein (5 mg/kg; A , A ) on levels when a glucose load (2 g/kg) is injected 2 h after oral administration of ambrein. in the symbols) or absence (open symbols) of 50 mgikg
rat blood glucose subcutaneously presence (closed mannoheptulose.
Control animals ( 0 , 0 ) received olive oil orally instead of ambrein. Each value is the mean result from 5 animals. Statistically significant from control: *P < 0.05. **P< 0.01. ***P< 0.001. Control + glucose ( 0 ) was further used as control for control + mannoheptulose
ORAL
levels (mg/lOO ml)”
0
(100) I91 f
FOLLOWING
only. Each value is the mean
Blood glucose
Control
(5) Control
Severely diabetic
I ml/animal)
RATS
+ glucose
( 0 ).
200
Z
3 S 3
+ Loading ;
2j9
5
Time(h)
i
s
ii
148
Joseph, 1985). Mannoheptulose is an inhibitor of glucose phosphorylation and glucose-stimulated insulin secretion (Henquin et al., 1986; Zawalich et al., 1986; Aprille et al., 1987; Choy et al., 1987; Grill et al., 1987; Grimaldi, 1987; Zawalich et al., 1987; Guest et al., 1989a,b). The present experiments demonstrate that ambrein can reduce the blood glucose of rats. These effects were only produced in non-diabetic rats, moderate alloxan-diabetic rats and glucose-loaded rats. In contrast, ambrein did not reduce the blood glucose levels of severely diabetic rats or in the presence of mannoheptulose. In the light of these findings, the mechanism by which ambrein lowers the blood glucose level of rats may be due to an effect on glucose-stimulated insulin release from beta-cells, since the hypoglycemic effect of ambrein is not changed in the presence of glucose injection, but is abolished in the presence of mannoheptulose and severe beta-cell destruction. However, further study is necessary to reveal the exact mechanism of the hypoglycemic activity of ambrein.
Grill. V.. Westberg, M. and Ostcnson. C. (19X7) Beta ccl1 insensitivity
Grimaldi.
rapidly
Siddle,
of the biosynthesis Coordinate
translational
all, granule
R.T.
and Nosek,
acute alteration
M.T.
(1987)
G..
Brennan.
W.A..
Mitochondrial
Kelley.
function
of the endogenous insulin-to-glucagon
Biochen~ic*rr/ md
after
matrix
constituents.
Joco-rd
isolated
J.C..
(1(3X6)
mannoheptulose Dunn.
J.. Sheehan,
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This study was supported by Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
for
hyperglycemia.
Owerhach.
Acknowledgement
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