ARTICLE
Auteur(s) :, Dharam Paul Chaudhary, Ravneet Kaur Boparai,
Rajeshwar Sharma, Devi
Dayal Bansal*
Department of Biochemistry, Panjab University,Chandigarh.
India-160014
Introduction
Decreased insulin sensitivity is recognized as a major metabolic
feature of type-2 diabetes and is one of the earliest detectable
abnormalities in persons who are prone to develop type-2 diabetes.
It is becoming increasingly clear that dietary nutrients can
modulate insulin action in a number of target tissues. In rats,
there is evidence that feeding sucrose rich diet impairs insulin
action [1, 2]. Sucrose feeding has long been reported to cause
elevated levels of insulin and triglycerides in rats [3, 4].
Increased triglyceride levels have been shown to be associated with
impaired insulin action [5]. Further, as sucrose is more rapidly
digested than other carbohydrates, different post prandial glycemic
curves (glycemic indices) with a corresponding difference in
stimulation of insulin secretion may affect insulin action [6].
Magnesium is an important component of many unprocessed foods, such
as whole grains, nuts, and green leafy vegetables and it is largely
lost during the processing of some foods [7]. Low extra-cellular
plasma and intra-cellular erythrocyte magnesium content has also
been shown to be associated with insulin resistance [8, 9]. Serum
magnesium concentrations have been shown to correlate inversely
with glucose disposal in diabetic patients and magnesium
administration has been found to increase utilization of
carbohydrates [10]. Our own studies have also shown that magnesium
deficiency occurs in alloxan induced experimental diabetes in rats
[11] and supplementation of magnesium to diabetic rats reverses
some of the effects caused by magnesium deficiency [12]. We also
found that diabetic patients have low magnesium levels [13].
Paolisso et al. [9] have demonstrated that there is a close
relationship between insulin, glucose homeostasis and
intra-cellular erythrocyte magnesium concentration. A close
relationship between hypomagnesemia and insulin resistance has been
reported in diabetic patients [8, 14]. Hypomagnesemia has been
implicated in the pathogenesis of ketoacidosis associated insulin
resistance. Further, in addition to the poor glycemic control,
magnesium deficit is an important predisposing factor for the
development of vascular changes implicated in diabetes, including
increased vasomotor tone and platelet reactivity [15]. Low serum
magnesium level has been reported to be a strong, independent
predictor of incidence of type-2 diabetes [16]. Lopez et al. [17]
have also suggested a significant inverse association between
magnesium intake and diabetes. Higher intake of magnesium has been
reported to have a protective role in reducing the risk of
developing type-2 diabetes [18]. Keeping in view the above
observations, the present study was designed to examine the
combined effect of a low magnesium high sucrose diet on the
development of insulin resistance in rats.
Materials and methods
Chemicals
RIAK kit for insulin was procured from Bhabha Atomic Research
Center, Mumbai, India. Reagent kits for glucose, triglycerides,
cholesterol and HDL-cholesterol estimation were procured from
Humane Gmbh D-65205, Germany. Methyl thymol blue (MTB), poly vinyl
pyrrolidine (PVP) and ethylene glycol tetra acetic acid (EGTA) were
from Sigma Chemical Company, St. Louis MO. USA and were kindly
provided by Prof. Ronal R. MacGregor, Department of Anatomy and
Cell Biology, University of Kansas Medical Center, Kansas City,
Kansas, USA. All other chemicals used were of analytical grade.
Animals and diet
Male wistar rats each weighing approximately 130 g were obtained
from the Central Animal House, Panjab University, Chandigarh. The
animals were kept in polypropylene cages under controlled
conditions of temperature and light. The rats were randomly divided
into four groups of six animals each. Group I was fed a synthetic
control diet, group II was fed a low magnesium diet, group III was
fed a sucrose rich diet while group IV was fed a diet low in
magnesium and high in sucrose. The animals were fed these
experimental diets for three months. The composition of the diets
is shown in table 1( Table 1
). The rats were given feed in small metal dishes just before the
beginning of dark cycle. Any spillage was collected in the morning
and its weight equivalent added to following day’s feed. Diets were
freshly made every 3-4 days and stored at 4 oC. The rats
were allowed free access to deionized water to avoid consumption of
magnesium from normal drinking water.
Table 1 Composition of the experimental diet (g/kg
of diet)
|
Ingredients
|
Normal diet
|
Magnesium deficient diet
|
Sucrose rich diet
|
High sucrose low magnesium diet
|
|
Sucrose
|
__
|
__
|
658.0
|
658.0
|
|
Cornstarch
|
658.0
|
658.0
|
__
|
__
|
|
Casein
|
188.0
|
188.0
|
188.0
|
188.0
|
|
Methionine
|
1.9
|
1.9
|
1.9
|
1.9
|
|
Gelatin
|
14.1
|
14.1
|
14.1
|
14.1
|
|
Safflower Oil
|
41.4
|
41.4
|
41.4
|
41.4
|
|
Bran
|
37.6
|
37.6
|
37.6
|
37.6
|
|
Vitamin Mix a
|
9.4
|
9.4
|
9.4
|
9.4
|
|
Mineral Mix b
|
49.7
|
49.7
|
49.7
|
49.7
|
aSupplied per kilogram of vitamin mix: 3 g thiamine
mononitrate, 3 g riboflavin, 3.5 g pyridoxine HCl, 15 g
nicotinamide, 8 g d-calcium pantothenate, 1 g folic acid, 0.1 g
d-biotin, 5 mg cyanocobalamine, 12.5 mg cholecalciferol, 25 mg
acetomenaphthone, 600 mg vitamin A acetate, 22 g dl
-α-tocophenylacetate and 10 g choline chloride.
bSupplied per kilogram of mineral mix: 65.2 g NaCl,
105.7 g KCl, 200.2 g KH2PO4, 40.0 g
FeCH3O2.5H2O, 512.4 g
CaCO3, 0.8 g KI, 0.9 g NaF, 1.4 g
CuSO4.5H2O, 0.4 g MnSO4 and 0.05 g
CaNH3.
The Normal and Sucrose rich diets also contain 30.5 g
MgSO4.7H2O and 38.8 g
MgCO3.3H2O per kg of mineral mix.
Biochemical analysis
Blood samples were drawn every month from the orbital sinus of
light-ether-anaesthised, overnight-fasted rats and immediately
centrifuged at 2000 x g for 15 minutes at 4 oC. The
levels of plasma glucose, triglycerides, total cholesterol and
HDL-cholesterol were measured by enzymatic assays using commercial
kits. Plasma magnesium concentration was estimated
spectrophotometrically by the dye method using methyl thymol blue
[19]. For the estimation of RBC magnesium, red cells were washed
thrice with normal saline in cold centrifuge and finally packed, an
aliquot of RBCs was digested using digestion mixture
(HNO3:HClO4; 3:1) and dried to ash. After
appropriate dilution magnesium was analyzed as previously
explained. Plasma insulin levels were measured at the end of the
study by radioimmunoassay [20]. RBC insulin receptor assay was done
as described by Gambhir et al. [21]. The activity of post heparin
plasma lipoprotein lipase was measured by the method of Edward [22]
.
Statistical procedures
Data were analysed using one-way Anova. If the overall F value
obtained from the Anova was significant, post hoc analyses were
performed by Tukey’s test. Significance was set at p < 0.05. All
data were presented as means ± SD.
Results
The data in table 2( Table 2 )
represents the values of body weight, plasma glucose, triglyceride,
cholesterol, HDL-cholesterol, plasma magnesium as well as RBC
magnesium levels at the end of one month of feeding experimental
diets, whereas table 3( Table 3 ) and table 4( Table 4 ) depict the values of these
parameters at the end of two months and three months of feeding
respectively. Animals in groups II and IV showed a lesser weight
gain (p < 0.005) compared to control rats. As is evident from
these tables, the blood glucose levels of overnight-fasted animals
of group II, III and IV started increasing from the first month of
feeding the experimental diets and this effect was maximum in group
IV. At the end of the study, blood glucose levels were
significantly higher in group II, III and IV as compared to control
rats. However, the maximum increase was observed in group IV (60.29
%). ( Figure 1 ) shows that
there was a significant increase in insulin levels in groups II,
III and IV as compared to the control rats. However, insulin levels
of group IV were significantly higher when compared to groups II
and III. Table 5( Table 5 )
depicts the insulin binding to the erythrocyte insulin receptors
after three months of feeding experimental diets. The insulin
binding to the receptors was significantly decreased in group III
(p < 0.05) and group IV (p < 0.005), compared to control
rats. The triglyceride levels of group II, III and group IV showed
a significant increase (p < 0.005), compared to group I. There
was a significant increase in the plasma cholesterol levels in the
high sucrose group. A significant decrease (p < 0.005) in
HDL-cholesterol was noticed in the high sucrose low magnesium group
(group IV) compared to control rats. Plasma HDL-cholesterol levels
correlated neither with plasma triglyceride concentrations (p >
0.05) nor with gains in body weight (p > 0.05) The plasma, as
well as RBC magnesium levels, were decreased significantly (p <
0.005) in groups II and group IV, though no significant change was
observed in case of group III. ( Figure 2 ) presents
the results of post heparin plasma lipoprotein lipase activity at
the end of three months of feeding. A significant decrease was
observed in the activity of lipoprotein lipase of group IV animals
when compared to group I (p < 0.005), group II (p < 0.005)
and group III (p < 0.005) animals.
Table 2 Levels of plasma glucose, plasma
triglycerides, plasma cholesterol and HDL-cholesterol, plasma and
RBC magnesium levels at the end of one month of feeding
|
Parameters
|
Group I
|
Group II
|
Group III
|
Group IV
|
|
Body weight (g)
|
180.34±4.08
|
148.67±2.87
|
180.83±2.25
|
185.34±3.26
|
|
***
|
γγγ
|
γγγ
|
|
Glucose (mg/dL)
|
76.46±6.37
|
78.26±8.19
|
89.36±8.28
|
109.65±10.9
|
|
***,γγγ,##
|
|
Triglycerides (mg/dL)
|
54.7±8.74
|
52.78±13.60
|
84.72±20.01
|
84.72±17.81
|
|
*,γ
|
*,γ
|
|
Cholesterol (mg/dL)
|
54.45±2.71
|
60.0±7.30
|
65.55±5.02
|
60.00±8.43
|
|
*
|
|
HDL-Cholesterol (mg/dL)
|
25.24±4.28
|
24.09±2.63
|
24.09±2.63
|
23.44±3.04
|
|
Plasma Magnesium (mg/dL)
|
2.28±0.25
|
1.32±0.23
|
2.4±0.14
|
1.47±0.21
|
|
***,###
|
***,###
|
|
RBC Magnesium (mg/dL)
|
4.16±0.13
|
3.25±0.13
|
4.16±0.13
|
3.30±0.13
|
|
***,###
|
***,###
|
Table 3 Levels of plasma glucose, plasma
triglycerides, plasma cholesterol and HDL-cholesterol, plasma and
RBC magnesium levels at the end of two months of feeding
|
Parameters
|
Group I
|
Group II
|
Group III
|
Group IV
|
|
Body weight (g)
|
244.16±5.84
|
185.34±4.54
|
239.16±3.79
|
220.16±3.54
|
|
***
|
γγγ
|
***,γγγ,###
|
|
Glucose (mg/dL)
|
70.04±5.32
|
91.03±12.38
|
93.80±14.21
|
112.26±7.79
|
|
*
|
**
|
***,γγ,#
|
|
Triglycerides (mg/dL)
|
62.85±7.22
|
103.78±11.05
|
126.64±13.25
|
138.07±16.74
|
|
***
|
***,#
|
***,γγγ
|
|
Cholesterol (mg/dL)
|
61.67±4.08
|
66.67±8.16
|
68.34±9.83
|
73.34±8.16
|
|
HDL-Cholesterol (mg/dL)
|
22.78±2.39
|
24.03±4.90
|
24.80±4.14
|
24.50±3.72
|
|
Plasma Magnesium (mg/dL)
|
2.04±0.11
|
1.18±0.21
|
2.07±0.11
|
1.33±0.29
|
|
***,γγγ
|
***,###
|
|
RBC Magnesium (mg/dL)
|
4.16±0.13
|
3.06±0.12
|
4.16±0.13
|
3.02±0.14
|
|
***,γγγ
|
***,###
|
Table 4 Levels of plasma glucose, plasma
triglycerides, plasma cholesterol and HDL-cholesterol, plasma and
RBC magnesium levels at the end of three months of feeding
|
Parameters
|
Group I
|
Group II
|
Group III
|
Group IV
|
|
Body weight (g)
|
285±4.47
|
198±5.09
|
283.34±4.08
|
236.67±4.08
|
|
***
|
γγγ
|
***,γγγ,###
|
|
Glucose (mg/dL)
|
70.52±7.70
|
96.04±9.07
|
102.62±6.86
|
113.04±5.79
|
|
***
|
***
|
***,γγ
|
|
Triglycerides (mg/dL)
|
60.94±4.66
|
112.34±5.88
|
133.32±9.32
|
153.32±11.67
|
|
***
|
***,γγ
|
***,γγγ,##
|
|
Cholesterol (mg/dL)
|
56.08±6.24
|
57.42±6.35
|
80.45±9.26
|
61.37±8.67
|
|
***,γγγ
|
##
|
|
HDL-Cholesterol (mg/dL)
|
23.12±3.27
|
22.01±1.14
|
24.36±0.71
|
17.35±2.93
|
|
***,γ,###
|
|
Plasma Magnesium (mg/dL)
|
2.16±0.13
|
1.23±0.29
|
2.23±0.21
|
1.23±0.14
|
|
***,###
|
***,###
|
|
RBC Magnesium (mg/dL)
|
4.14±0.12
|
2.68±0.18
|
4.21±0.21
|
2.63±0.17
|
|
***,###
|
***,###
|
Table 5 Insulin receptor assay of erythrocytes
after three months of feeding experimental diets
|
Insulin binding (%)
|
|
Group I
|
9.47±0.32
|
|
Group II
|
8.75±0.57
|
|
Group III
|
8.32±0.61
|
|
*
|
|
Group IV
|
6.81±0.72
|
|
***,γγγ , ###
|
Discussion
The present study clearly shows that a low magnesium high sucrose
diet did not cause obesity, as the body weight of rats of group IV
was almost equal to control rats. Previous studies have shown that
magnesium deficiency leads to a decrease in body weight [23-25]
whereas sucrose has been shown to either cause an increase in body
weight or to not affect body weight [3, 26, 27]. Since the present
work has been carried out to study the combined effect of low
magnesium high sucrose diet it seems that even as sucrose increases
body weight, as observed in group III rats, low magnesium at the
same time has been shown to cause a lesser gain in body weight as
seen in group II animals. Thus the weight gained due to high
sucrose feeding is compensated by a low magnesium diet and
therefore the overall effect observed was that the animals of group
IV had a body weight comparable to that of the normal rats.
Hyperglycemia is the hallmark of diabetes mellitus. The
significant rise in plasma blood glucose and the corresponding
increase in the plasma insulin levels in animals of group II, III
and IV, compared to control rats, is an indication of disturbed
glucose homeostasis and insulin resistance. The insulin resistant
state is basically a pre-diabetic condition, which, if not
controlled, usually culminates in diabetes later on. Many
scientists have already established sucrose moiety of the diet as a
detrimental component in the aetiology of diabetes mellitus through
insulin resistance [2, 27, 28]. It has been widely reported that
inclusion of sucrose in the diet for 2-8 weeks can increase fasting
blood glucose, plasma insulin and total triglycerides in
non-insulin dependent diabetes mellitus, non-diabetic
hyperinsulinemic and normal humans [29, 30]. There are many reasons
why these impairments occur. Sucrose, due to its rapid digestion
and high glycemic index, gives different post-prandial plasma
glycemic curves (glycemic indices) with corresponding differences
in the stimulation of insulin secretion and subsequent insulin
action. Reports in the literature show that most of the
characteristic effects of high sucrose diets are thought to be
caused by the fructose component of the diet [31]. Fructose
metabolism bypasses the control exerted at phosphofructokinase, one
of the key regulatory enzymes in glycolysis. Because pyruvate
kinase is stimulated by fructose-1-phosphate, there is a strong
drive for the production of pyruvate and thus other metabolic
intermediates, such as lactate, acetyl-CoA and malonyl-CoA.
Fructose is also involved in gluconeogenesis. Our direct
demonstration of hyperglycemia and hyperinsulinemia in sucrose fed
rats is consistent with data published previously. It has been
shown that chronic feeding of fructose, a sucrose component, alters
the activity of specific enzymes regulating hepatic carbohydrate
metabolism and both a decrease in the activity of glucokinase [32,
33] and an increase in glucose-6-phosphatase [34, 35] activity have
been described. Furthermore, fructose feeding has been shown to
lead to a decrease in the ability of insulin to suppress activation
of hepatic glucose-6-phosphatase and fructose-1,6-bisphos-phatase
activity [35]. Studies in rats have shown a close association
between decreased insulin sensitivity with high sucrose or high
fructose diets and fasting hypertriglyceridemia [2, 28].
Low serum magnesium levels have been shown to be implicated in
the pathogenesis of type-2 diabetes. Earlier studies suggest
several possible mechanisms whereby low serum magnesium levels may
lead to the development of type-2 diabetes. First of all, it is an
essential cofactor in reactions involving phosphorylation, thus
magnesium deficiency could impair the insulin signal transduction
pathway [36, 37]. Second, low serum or erythrocyte magnesium levels
may affect the interaction between insulin and insulin receptor by
decreasing hormone receptor affinity or by increasing membrane
micro viscosity [38]. Finally, magnesium can also be a limiting
factor in carbohydrate metabolism, since many of the enzymes in
this process require magnesium as a cofactor during reactions that
utilize the phosphorus bond [36, 37, 39, 40]. Our study showed
depressed levels of plasma as well as RBC magnesium, reflecting the
body magnesium status, in groups II and IV. In animal models,
hypomagnesemia induced by low magnesium intake triggers severe
insulin resistance, which was shown to be partially dependent on
deficient tyrosine kinase activity on post receptor pathway of
insulin in muscle cells [41]. In healthy humans, a study of short
term low magnesium diet showed that it reduces serum and
intracellular magnesium and produced insulin resistance, using a
minimal model [42]. An intriguing theory suggested by Tongyai et
al. [43] is that a low erythrocyte magnesium content can alter
membrane microviscosity, and this might have impaired the
interaction of insulin with its receptor on the membrane.
The most important finding of our study is the significant rise
in plasma triglyceride levels in group II and III. Increased
triglyceride levels have been associated in a number of
circumstances with impaired insulin action [6]. Thornburn et al.
[7] have also shown that even a short term and relatively mild
elevation of triglyceride levels is sufficient to produce a marked
impairment of peripheral insulin action. Further, an elevation in
blood triglyceride levels has been shown to reduce the number of
insulin receptors, thereby reducing insulin sensitivity [44]. Our
present finding may be interpreted as that the lower number of
cellular insulin receptors in high sucrose low magnesium diet fed
rats is the principal defect and the reason for insulin resistance.
Lipoprotein lipase, a key enzyme involved in the hydrolysis of
triglyceride rich particles, is an insulin sensitive enzyme. We
therefore speculate that the insulin resistance induced in our
study might have influenced lipoprotein lipase. Pijkalisto et al.
[45] were the first to report that post heparin plasma and adipose
tissue lipoprotein lipase is reduced in NIDDM subjects. The fact
that post heparin plasma lipoprotein lipase is reduced in rats with
hypertriglyceridemia is consistent with earlier observations,
suggesting that insulin resistance may influence LPL activity [46,
47]. Reduced activity of lipoprotein lipase has also been
associated with high sucrose intake [48].
Elevated plasma cholesterol concentrations along with the higher
gains in body weight in Group III animals suggests that a high
sucrose diet leads to hyperlipidemia and could also cause obesity.
Roberts et al. [49] reported an increase in body weight, plasma
total cholesterol, VLDL-cholesterol, LDL-cholesterol and
triglyceride concentrations in rats fed a high sucrose diet. They
concluded that a high sucrose diet induces changes in lipoprotein
lipase and VLDL receptor and also decreases TG-rich lipoprotein
clearance, contributing to increased plasma lipids and obesity.
Derangement of lipid metabolism in diabetes mellitus is well known
and an increase in cholesterol levels together with a decrease in
the HDL-cholesterol has been reported [50]. The significant
decrease in the plasma HDL-cholesterol levels in the high sucrose
low magnesium group (group IV) is a clear indication of the
disturbed lipid metabolism in these animals, suggesting that
chronic feeding of a diet high in sucrose and low in magnesium may
ultimately lead to a state of insulin resistance in rats.
Conclusion
Hypomagnesemia is fairly common and is a potential risk factor for
the development of type-2 diabetes. A sucrose rich diet has clearly
been established as a critical component for inducing fasting
hyperglycemia in rats, which may further lead to insulin
resistance. Combined together, a diet high in sucrose and low in
magnesium may possibly be used to raise a type-2 diabetic rat
model. This study clearly indicates that a low magnesium high
sucrose diet induces substantial hyperglycemia,
hypertriglyceridemia and hyperinsulinemia in rats. Since the
above-mentioned three findings are critical in the initial stages
of diabetes, it may therefore be concluded that an insulin
resistant rat model could be developed by feeding a diet low in
magnesium and high in sucrose, and this model could possibly be
used to study the effects of various anti-diabetogenic drugs.
References
1 Grimditch G, Barnard R, Hendricks L,
Weitzman D. Peripheral insulin sensitivity as modified by diet
and exercise training. Am J Clin Nutr 1988; 48: 38-43.
2 Storlein LH, Kraegen EW, Jenkins AB,
Chisholm DJ. Effect of sucrose vs starch diet on in vivo
insulin action, thermogenesis and obesity in rats. Am J Clin Nutr
1988; 47: 420-7.
3 Reiser S, Michaelis OV, Putney, Hallfrish J.
Effect of sucrose feeding on intestinal transport of sugars in two
strains of rats. J Nutr 1975; 105: 984.
4 Laube H, Klor HU, Fusgganger R,
Preiffer EF. The effect of starch, sucrose, glucose and
fructose on lipid metabolism in rats. Nutr Metab 1973; 15: 273.
5 Jenkins DJA, Wolever TMS, Jenkins AL,
Josse RG, Wong GS. The glycemic response to carbohydrate
food. Lancet 1984: 1388-91.
6 Thornburn W, Leonard HS, Arthus BJ, Sue K,
Kraegen EW. Fructose induced in vivo insulin resistance and
elevated plasma triglyceride levels in rats. Am J Clin Nutr 1989;
49: 1155-63.
7 Saris NE, Mervaala E, Karppanen H,
Khwaja JA, Lewenstam A. Magnesium: an update on
physiological, clinical and analytical aspects. Clin Chim Acta
2000; 294: 1-26.
8 Moles LW, Mullen JK. Insulin resistance and
hypomagnesemia; case report. BMJ 1982; 285: 62.
9 Paolisso G, Scheen AS, D’Onofrio F,
Lefevbre PJ. Magnesium and glucose homeostasis. Diabetologia
1990; 33: 511-4.
10 Yajnik CS, Smith RF, Hockaday TDR,
Ward NI. Fasting plasma magnesium concentrations and glucose
disposal in diabetes. BMJ 1984; 288: 1032-4.
11 Hans CP, Chaudhary DP, Bansal DD. Magnesium
deficiency increases oxidative stress in rats. Ind J Exptl Biol
2002; 40: 1275-9.
12 Hans CP, Chaudhary DP, Bansal DD. Effect of
magnesium supplementation on oxidative stress in alloxan diabetic
rats. Magnesium Research 2003; 16: 13-9.
13 Hans CP, Sialy R, Bansal DD. Hypomagnesemia in
diabetic patients: correlation with oxidative stress. Intl J Diab
Dev Countries 2002; 22: 122-31.
14 Paolisso G, Sgambato S, Gambardella A,
Pizza G, Tesauro P, Varricchio M, d’Onofrio F.
Daily magnesium supplements improves glucose handling in elderly
subjects. Am J Clin Nutr 1992; 55: 1161-7.
15 Nadler JL, Malayan S, Luong H, Shaw S,
Natarayan RD, Rude RK. Intra-cellular free magnesium
deficiency plays a key role in increased platelet reactivity in
type-2 diabetes mellitus. Diabetes Care 1992; 15: 835-41.
16 Kao WH, Folsom AR, Javier FN,
Jing-Ping M, Watson RL, Brancati FL. Serum and
dietary magnesium and risk for type-2 diabetes mellitus. Arch
Intern Med 1999; 159: 2151-9.
17 Lopez-Ridaura R, Willet WC, Rim EB,
Liu S, Satampfer MJ, Manson JE, Hu HB.
Magnesium intake and risk of type-2 diabetes in men and women.
Diabetes Care 2004; 27: 134-40.
18 Song Y, Manson JE, Buring JE, Liu S.
Dietary magnesium intake in relation to plasma insulin levels and
risk of type-2 diabetes in women. Diabetes Care 2004; 27:
59-64.
19 Connerty HV, Lau HSC, Briggs AR.
Spectrophotometric determination of magnesium by use of methyl
thymol blue. Clin Chem 1971; 17: 661-2.
20 Berson SA, Yallow RS. General principles of
radioimmunoassay. Clin Chem Acta 1968; 22: 51-4.
21 Gambhir KK, Archer JA, Carter L. Insulin
radioreceptor assay for human erythrocytes. Clin Chem 1977; 23:
1590-6.
22 Edward D C. Lipoprotein Lipase In. Methods Enzymology (V
1962; 72: 542-5.
23 Bunce GE, Li BW, Price NO, Greensreet R.
Distribution of calcium and magnesium in rat kidney homogenate
fractions accompanying magnesium deficiency induced
nephrocalcinosis. Exp Molec Path 1974; 21: 16-28.
24 El Hindi HM, Amer HA. Effect of thiamine, magnesium
and sulphate salts on growth, thiamine levels and serum lipid
constituents in rats. J Nutr Sc Vitaminol 1989; 35: 505-10.
25 Guex E, Mazur A, Cardot P, Rayssiguier Y.
Magnesium deficiency affects plasma lipoprotein composition in
rats. J Nutr 1991; 121: 1222-7.
26 Buckdorfer KR, Kari-Kari BPB, Kahn IN,
Yudkin J. Activity of lipogenic enzymes and plasma
triglyceride levels in the rat and chicken as determined by nature
of dietary fat and dietary carbohydrate. Nutr Metab 1972; 14:
228-37.
27 Hallfrisch J, Lazar F, Jorgenson C,
Reiser S. Insulin and glucose responses in rats fed sucrose or
starch. Am J Clin Nutr 1979; 32: 787-93.
28 Wright DW, Hansen RI, Mondon CE,
Reavon GM. Sucrose induced insulin resistance in rat;
modulation by exercise and diet. Am J Clin Nutr 1983; 38:
879-83.
29 Coulston AM, Hollenback CB, Swislcoki ALM,
Chen YD, Reavon GM. Deleterious metabolic effect of high
carbohydrate, sucrose containing diets in patients with non insulin
dependent diabetes mellitus. Am J Med 1987; 82: 213-20.
30 Hollenbeck CB, Coulston AM, Reavon GM.
Glycemic effect of carbohydrates; a different perspective. Diabetes
Care 1986; 9: 641-7.
31 Mayes PA. Intermediary metabolism of fructose. Am J Clin
Nutr 1993; 58(suppl): 754S-765S.
32 Blumenthal MD, Abraham S, Chaikoff IL. Dietary
control of liver glucokinase activity in the normal rat. Arch
Biochem Biophys 1964; 104: 215-24.
33 Zakim D, Pardini RS, Herman RH,
Sauberlich HE. Mechanism for the differential effect of high
carbohydrate diet on lipogenesis in rat liver. Biochem Biophys Acta
1967; 144: 242-51.
34 Fitch WM, Chaikoff IL. Extent and patterns of
adaptation of enzyme activities in livers of normal rats fed diets
high in glucose and fructose. J Biol Chem 1960; 235: 554-7.
35 Touvinen CGR, Bender AE. Some metabolic effects of
prolonged feeding of starch, sucrose, fructose and carbohydrate
free diet in the rat. Nutr Metab 1975; 19: 161-72.
36 Elin RJ. Magnesium metabolism in health and disease. Dis
Mon 1988; 34: 161-218.
37 Styler L. Biochemistry 3rd ed. New York, NY: WH Freeman
&Co., 1988.
38 Tongyai S, Rayssiguier Y, Motta C,
Gueux E, Maurois P, Heaton FW. Mechanism of
increased erythrocyte membrane fluidity during magnesium deficiency
in weanling rats. Am J Physiol 1989; 257(pt 1): C270-C276.
39 Caro JF, Triester S, Patel VK,
Tapscott EB, Frazier NL, Dohm GL. Liver glucokinase:
decreased activity in patients with type-2 diabetes. Horm Metab Res
1995; 27: 19-22.
40 Matschinsky FM. Glucokinase as glucose sensor and
metabolic signal generator in pancreatic beta-cells and
hepatocytes. Diabetes 1990; 39: 647-52.
41 Suarez A, Pulido N, Casla A, Casanova B,
Arricta EJ, Rovira A. Impaired tyrosin kinase activity of
muscle insulin receptors from hypomagnesemic rats. Diabetologia
1995; 38: 1262-70.
42 Nadler JL, Buchanan T, Natarajan R,
Antonipilai I, Bergman R, Rude R. Magnesium
deficiency produces insulin resistance and increased thromboxane
acitivity. Hypertension 1993; 21: 1024-9.
43 Tongyai S, Motta C, Rayssiguier Y,
Heaton FW. Erythrocyte membrane in magnesium deficiency. Am J
Nutr 1985; 4: 399; (abstract).
44 Bieger WP, Michel G, Barwich D, Wirth A.
Diminished insulin receptors on monocytes and erythrocytes in
hypertriglyceridemia. Metabolism 1984; 33: 982-7.
45 Pijkalisto OJ, Smith PH, Brunzell JD.
Determinants of human adipose tissue lipoprotein lipase. Effect of
diabetes and obesity on basal- and diet-induced activity. J Clin
Invest 1975; 56: 1108-17.
46 Pollare T, Vessby B, Lithel H. Lipoprotein
lipase activity in skeletal muscle is related to insulin
sensitivity. Atherosclerosis 1991; 11: 1192-203.
47 Kern PA, Ong JM, Saffari B, Carty J. The
effect of weight loss on the activity and expression of adipose
tissue lipoprotein lipase in very obese humans. N Engl J Med 1990;
322: 1053-9.
48 Sheorain VS, Mattock MB, Subramaniun D.
Mechanism of carbohydrate induced hypertriglyceridemia. Plasma
lipid metabolism in mice. Metabolism 1980; 29: 924-9.
49 Roberts CK, Barnard RJ, Liang KH,
Vaziri ND. Effect of diet on adipose tissue and skeletal
muscle VLDL receptor and LPL: implications for obesity and
hyperlipidemia. Atherosclerosis 2002; 161: 133-41.
50 Tall AR. Plasma high density lipoproteins; Metabolism
and relationship to atherogenesis. J Clin Invest 1990; 86:
379-84.
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