Pancreatic Beta Cell Toxicity by Streptozotocin Anomers

Abstract

D-glucose in the pyranose (ring) form exists as two anomers. The alpha-anomer is more effective than the beta-anomer in promoting insulin secretion, suppressing that of glucagon, and protecting beta-cells against alloxan toxicity. Streptozotocin (SZ), a beta cell toxin, is composed of a cytotoxic moiety, 1-methyl 1-nitrosourea, attached to carbon-2 of glucose and exists as either of two anomers in the pyranose form. In 24-hour-fasted male rats, predominantly alpha- or predominantly beta-SZ was injected intravenously and plasma glucose levels were obtained 48 hours later. The alpha-anomer produced significantly greater beta-cell necrosis at doses of 30, 35, and 40 mg./kg. body weight. At higher doses, no differences between the alpha and beta anomers were observed. 3-O-Methyl glucose (3-OMG) protected against both SZ anomers; however, the alpha-SZ remained more toxic. Larger doses of glucose protected against the lower doses of SZ and, under such conditions, the individual glucose anomers appeared equally potent. Finally, mannitol at comparable molar concentrations was ineffective in protecting against the SZ toxicity. This study suggests that streptozotocin's beta cell toxicity is mediated through recognition by the beta cell. In addition, 3-OMG and, to a lesser but significant extent, glucose were shown to protect against the streptozotocin toxicity, whereas mannitol did not.

Rat‐liver‐type phosphofructokinase mRNA

“…Male Sprague-Dawley rats (170-190 g) were made diabetic by intravenous injection of streptozotocin (50 mg/kg body mass, Sigma Chemical Co., St. Louis, MO) after starvation for 20 h as described [25]. Plasma glucose was assayed 2 days after the treatment by the glucose oxidase method 1261.…”

“…The catalytic activity and immunoreactivity of PFK-L in the liver were demonstrated to decrease in starved rats and diabetic rats, and to be restored to the normal level or even more increased in these animals by refeeding and insulin treatment, respectively [7, 81. The decrease in the level of PFK-L protein in starved rats and diabetic rats has been reported to be the result of its Male Sprague-Dawley rats (170-190 g) were made diabetic by intravenous injection of streptozotocin (50 mg/kg body mass, Sigma Chemical Co., St. Louis, MO) after starvation for 20 h as described [25]. Plasma glucose was assayed 2 days after the treatment by the glucose oxidase method 1261.…”

The High-Fat Diet–Fed Mouse

“…These two needs require reliable and clinically relevant experimental models. Most animal models do not, however, fulfill such requirements, since they are based on monogenic disorders of little relevance for human diabetes (3)(4)(5) or on chemical destruction of ␤-cells, which is also of less clinical relevance (6,7). An important and relevant model, however, is the high-fat diet-fed C57BL/6J mouse model.…”

Insulin-mimetic action of vanadyl complexes.

“…In the 1980's, the vanadate ion was shown to mimic the action of insulin in intact cell systems [13][14][15][16][17][18]. Heyliger et al in 1985 [19], followed by Meyerovitch et al in 1987 [20] and Plondel et al [21] found that the inclusion of sodium vanadate in the drinking water of streptozocin (STZ) [22]-induced diabetic rats alleviated some symptoms of diabetes, resulting in the normalization of blood glucose levels. In these studies, sodium vanadate was exclusively used.…”