The Central Effect of Chromium on Glucose Metabolism

We read your article dealing with the effect of chromium on monoamine production with great interest. In our experiments, we also observed central effects of chromium picolinate on glucose metabolism.

We conducted our study on adult, male Wistar rats. After a control oral glucose tolerance test (OGTT), the animals showing pathologic glucose tolerance were excluded from the study. Surgery was performed under microscopic control with the help of a stereotaxical device. A hole of 2-3 mm in diameter was drilled into the skull of the animals above the ventromedial hypothalamus as deep as the level of the dura mater [6]. A guiding cannula was placed on the dura mater above the area of the ventromedial hypothalamus (VMH) and it was fixed with dentist’s acrilate to the skull. After a recovery period of one week, the animals were divided into 3 groups, with 12 animals in each group. Administering tubes were placed into the guiding cannulas. The agents were delivered into the VMH through the administering tubes with the help of a Hamilton syringe and a microinjection pump. One group was given chromium picolinate (2 mg/ml) [1] pretreatment, then 75 minutes later 0.0037 M streptozotocin (STZ) [2]. A second group was given only STZ [3] and a third sham-operated group was given the same amount of saline. Pump rate of the injections was 1 μl/min/side. One μl of each agent was given to both sides. Before removing the administering tubes, we waited 1 minute to let the agents diffuse from the area of administration.

An acute OGTT was made 15 minutes after the administration of the microinjections. After taking the animals’ fasting blood glucose level, OGTT was performed. Blood glucose levels were measured 9, 18, 30, 60 and 120 minutes after the administration of 0.5 g/ml/100 g d-glucose solution [4]. After 15 hours fasting, the animals were given an intraperitoneal injection of 6 NE/kg of insulin. Food intake was measured then 2, 4 and 24 hours after the injection. Blood glucose levels were measured simultaneously. Plasma insulin and leptin levels were determined with the help of radioimmunoessay kits. Histological studies were performed to determine if the guiding cannulas were positioned correctly.

Acute OGTT showed a significant difference between the STZ-treated and the both STZ- and chromium treated groups (p < 0.002). The group that was administered only STZ showed pathologically elevated blood sugar levels. The chromium-pretreated group did not show significant differences in their blood sugar levels compared to the sham-operated group. In chronic OGTT, the highest blood sugar level values developed after 120 minutes. Intrahypothalamically applied STZ also caused a disturbance in food intake after intraperitoneally administered insulin. In the first 2 hours no significant changes could be observed, but after 4 hours animals that were only treated with STZ consumed significantly more food than the two other groups. There was no significant difference between the chromium pretreated and the sham operated group. After 24 hours this pattern was still apparent. Blood glucose values measured simultaneously with these measurements showed no significant differences in the 3 groups. There was no significant difference in insulin and leptin levels either.

As in previous studies, STZ microinjection of the VMH caused pathologically elevated blood sugar levels in both acute and chronic OGTTs. Centrally applied STZ caused abnormalities of food intake after intraperitoneally administered insulin (Table [1]). There was no significant difference in insulin and leptin levels between the different groups. In our experiment, chromium pretreatment hindered STZ to cause diabetes-like symptoms. According to previous studies, intrahypothalamically applied STZ kills the glucose monitoring (GM) neurons. We suspect that local changes in cerebral chromium levels might have an effect on these glucose-receptor neurons [5] [7].

Table 1 Changes in the glucose levels at different times in acute and chronic OGTTs. STZ microinjection applied and the VMH induced pathological elevation of blood glucose levels in both acute and chronic OGTTs. STZ caused abnormalities in food intake after intraperitoneally administered insulin. The local changes in cerebral chromium levels might have an effect on glucose levels Glucose levels inacute OGTT(30 min)(mmol/l) Glucoselevels inacute OGTT(120 min)(mmol/l) Glucoselevels inchronicOGTT(120 min)(mmol/l) I.p. insulin-induced food intake (4 h) (g) I.p. insulin-induced food intake (24 h) (g) Controls 9.2 7.2 7.1 7.6 31.7 STZ 13.8 8.9 7.9 10.5 37.2 STZ + Cr(III) 9.8 7.3 7.1 8 29.5

References

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• 5 Hoyer S. Memory function and brain glucose metabolism.  Pharmacopsychiatry. 2003;  36 S 62-67
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