Abstract
The intake of dietary fructose has undergone a marked increase around the world, especially
the developed countries, in recent times. Stevioside, a glycoside contained in the
leaves of Stevia rebaudiana Bertoni (Compositae), was used to screen the effect induced by a diet containing 60 % fructose
on insulin resistance in rats. Single oral administration of stevioside for 90 min
decreased plasma glucose concentrations in a dose-dependent manner in rats receiving
fructose-rich chow for four weeks. In addition, insulin action on glucose disposal
rate was measured using the glucose-insulin index, the product of the areas under
the curve of glucose, and insulin during the intraperitoneal glucose tolerance test.
Oral administration of stevioside (5.0 mg/kg) in rats given four weeks of fructose-rich
chow for 90 min reversed the value of glucose-insulin index, indicating that stevioside
has the ability to improve insulin sensitivity in this insulin-resistant animal model.
Time for the loss of plasma glucose lowering response to tolbutamide (10.0 mg/kg,
i. p.) in fructose-rich chow fed rats was also markedly delayed by repeated stevioside
treatment three times daily compared to the vehicle-treated group. The plasma glucose-lowering
activity of tolbutamide was introduced to account for varying levels of endogenous
insulin secretion, and is widely used as the indicator of insulin resistance development.
Thus, it provided the supportive data that repeated oral administration of stevioside
delayed the development of insulin resistance in rats on a high-fructose diet. Increased
insulin sensitivity by stevioside administration was further identified using the
plasma glucose-lowering action of exogenous insulin in streptozotocin-induced diabetic
rats (STZ-diabetic rats). Oral administration of stevioside at 0.2 mg/kg three times
daily into STZ-diabetic rats for ten days increased the response to exogenous insulin.
Taken together, this demonstrated that oral administration of stevioside improves
insulin sensitivity, and seems suitable as an adjuvant for diabetic patients and/or
those that consume large amounts of fructose.
Key words
Fructose-rich chow - Insulin resistance - Intraperitoneal glucose tolerance test -
Stevioside - Tolbutamide
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Prof. Juei-Tang Cheng
Department of Pharmacology
College of Medicine · National Cheng Kung University · Tainan City · Taiwan 70101
· R.O.C
Phone: +886 (6) 237-2706
Fax: +886 (6) 238-6548 ·
Email: jtcheng@mail.ncku.edu.tw
