Fructose-fed streptozotocin-injected rat : an alternative model for type 2 diabetes.
The principal objective of this study was to develop an alternative non-genetic rat model for type 2 diabetes (T2D). Six-week-old male Sprague-Dawley rats (190.56 ± 23.60g) were randomly divided into six groups namely: Normal Control (NC), Diabetic/Streptozotocin Control (STZ), Fructose-10 (FR10+STZ), Fructose-20 (FR20+STZ), Fructose-30 (FR30+STZ) and Fructose-40 (FR40+STZ) and were fed a normal rat pellet diet ad libitum for 2 weeks. During this period, the two control groups received normal drinking water whilst the fructose groups received 10, 20, 30 and 40% fructose in drinking water ad libitum respectively. After two weeks of dietary manipulation, all groups except the NC group received a single injection (i.p.) of streptozotocin (STZ) (40mg/kg BW) dissolved in citrate buffer (pH 4.4). The NC group received only a vehicle buffer injection (i.p.). One week after the STZ injection, animals with non-fasting blood glucose >300 mg/dl were considered as diabetic. Three weeks after the STZ injection, the animals in FR20+STZ, FR30+STZ and FR40+STZ were eliminated from the study due to the severity of diabetes and the FR10+STZ group was selected for the remainder of the 11 weeks experimental period. The significantly (p < 0.05) higher fluid intake, blood glucose, serum lipids, liver glycogen, liver function enzymes and insulin resistance (HOMA-IR) and significantly (p < 0.05) lower body weight, oral glucose tolerance, number of pancreatic β-cells and pancreatic β-cell functions (HOMA-beta) of FR10 group demonstrate that the 10% fructose-fed followed by 40 mg/kg of BW STZ injected rat can be an excellent alternative model for T2D. To validate this newly-developed model, an acute intervention trial study was conducted to investigate the anti-diabetic effects of L-Carnitine and white mulberry leaf tea extracts in the newly developed animal model of type 2 diabetes (T2D). Male Sprague-Dawley rats (mean BW 191.88g±16.40g) were randomly divided into 5 groups namely: Normal Control (NC), Diabetic/Streptozotocin control (FR10+STZ), Mulberry Tea Low (FR10+STZ+MTL, 0.25%), Mulberry Tea High (FR10+STZ+MTH, 0.5%), and L-Carnitine (FR10+STZ+CARN). In first three weeks, T2D was induced in all other groups except NC group by using above-mentioned procedure. Mulberry tea was supplied ad libitum and L-carnitine was administered to the FR10+STZ+CARN group at a concentration of 500mg/kg BW once daily during week 4-8 of the intervention trial. The FR10+STZ+CARN group had significantly (p < 0.05) lower total cholesterol, triglycerides, total proteins and fluid intake compared to the diabetic control (FR10+STZ). The NFBG non-significantly reduced in FR10+STZ+CARN group compared to the FR10+STZ group, whereas MT did not. FR10+STZ+MTL had significantly higher serum triglycerides level compared to the NC group, and significantly higher HDL-cholesterol and fluid intake compared to the FR10+STZ group. FR10+STZ+CARN and FR10+STZ+MT groups had significantly lower total proteins compared to NC and FR10+STZ groups, but significantly lower albumin compared to NC group only. The data of the this section of the study suggest that CARN may be effective in normalizing lipid profiles rather than blood glucose in diabetic rats which may aid in the reversal of insulin resistance. On the other hand, MT used in this study did not display any significantly beneficial anti-diabetic effects at least in this experimental condition.