Medicinus - Dexa Medica

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research original article
DISCUSSION
Figure 3. Effect of DLBS3233 (9 mg/kg body weight) on the HOMA level of Wistar strain rats.
In this study, we demonstrate the effect of DLBS3233
in insulin resistant animal model. The animals were
treated to be insulin resistant by administration of
high amount of fructose and glucose, which may
lead to uncontrolled insulin action. Previous studies
provide direct evidence that the insulin resistance
occurs due to changes in hepatic carbohydrate metabolism,
leading to increased hepatic glucose efflux
under basal conditions, and to a loss of the ability
of insulin to suppress hepatic glucose efflux. These
changes are most likely due to an effect of fructose
at several control steps in the regulation of hepatic
glycogenesis, glycogenolysis and/or gluconeogenesis.
8
Insulin resistant condition induced by treatment
of sugar showed that the levels of random glucose,
postprandial glucose, and fasting glucose as well
as insulin increased significantly when compared
to control group treated with only normal saline.
However, administration of DLBS3233 to the insulin
resistant rats for two weeks could reverse the levels
of glucose and insulin into the levels similar to those
of normal condition (Table 1 and Fig. 1). Insulin resistance
may occur through different mechanisms,
including defects in insulin binding and signal transduction,
or defects at the level of effector molecules
such as glucose transporters and enzymes involved
in carbohydrate metabolism. 9 DLBS3233 demonstrated
its activity in controlling blood glucose by
mediating the upregulation of PPARγ and GLUT4
MEDICINUS 24(1), January 2011
expression. Activation of PPARγ induces adipocyte
differentiation and lipid accumulation by adipocytes
through modulating numerous genes regulating
adipogenesis, lipid uptake and lipid metabolism. Result
of that study also indicated that DLBS3233 is a
glucose transport-stimulant as it upregulates GLUT4
expression significantly. 10
Fructose feeding may result in hypertriglyceridemia,
resistance to insulin-stimulated glucose uptake,
and impaired endothelium-dependent vasodilation,
but not in an elevation of arterial pressure. In
the fructose-fed rat, hypertriglyceridemia has been
attributed to impaired triglyceride removal due to
insulin resistance. 11 In addition, hypertiglyceridemia
also has a strong correlation with increased LDLcholesterol
and decreased HDL-cholesterol. 3 Results
of this study also showed that levels of other biological
parameters including total cholesterol, LDL,
and triglycerides were increased in insulin-resistant
model while the level of HDL for the insulin resistant
group decreased. However, the levels of those
biological parameters were back to normal when
DLBS3233 was administered in the treated rats. This
finding suggests that DLBS3233 posses the ability to
control the triglyceride and cholesterol level including
LDL and HDL level.
Furthermore, indirect method for assesment of
insulin resistance was also perfomed by determining
HOMA level. It is usually perfomed for early identification
of insulin resistant individuals as it is important
for the management strategies of diabetes
mellitus. HOMA (homeostasis model assesment) is a