The stimulatory effect of dopamine through dopamine D2 receptor on glucose-induced insulin secretion was studied in the pancreatic islets in vitro. Dopamine significantly stimulated insulin secretion at a concentration of 10-8 M in the presence of high glucose (20 mM). The higher concentrations of dopamine (10(-7)-10(-4)) inhibited glucose-induced insulin secretion in the presence of both 4 mM and 20 mM glucose. Stimulatory and inhibitory effect of dopamine on glucose-induced insulin secretion was reverted by the addition of dopamine D2 receptor antagonists such as butaclamol and sulpiride. Norepinephrine (NE) at 10(-4) M concentration inhibited the dopamine uptake as well as its stimulatory effect at 10(-8) M concentration on glucose induced insulin secretion. Our results suggest that dopamine exerts a differential effect on glucose-induced insulin secretion through dopamine D2 receptor and it is essential for the regulation of glucose-induced insulin secretion by pancreatic islets.

In the present study dopamine was measured in the hypothalamus, brainstem, pancreatic islets and plasma, using HPLC. Dopamine D2 receptor changes in the hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151-2 in streptozotocin-induced diabetic and insulintreated diabetic rats. There was a significant decrease in dopatnine content in the hypothalamus (P<0.001), brainstem (P<0.001), pancreatic islets (P<0.001) and plasma (P<0.00I) in diabetic rats when compared to control. Scatchard analysis of [3H] YM-09151-2 in the hypothalamus of diabetic rats showed a significant decrease in Bax (P<0.001) and Kd, showing an increased affinity of D2 receptors when compared to control. Insulin treatment did not completely reverse the changes that occurred during diabetes. There was a significant decrease in B,nax (P<0.01) with decreased affinity in the brainstem of diabetic rats. The islet membrane preparation of diabetic rats showed a significant decrease (P<0.001) in the binding of [3H] YM-09 151-2 with decreased Kd (P<0.001) compared to control. The increase in affinity of D2 receptors in hypothalamus and pancreatic islets and the decreased affinity in brainstem were confirmed by competition analysis. Thus our results suggest that the decreased dopamine D, receptor function in the hypothalamus, brainstem and pancreas affects insulin secretion in diabetic rats, which has immense clinical relevance to the management of diabetes.

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Caþ F2 ; low-Ca (0·25 %) diet (LCD), Ca2 F2; NCD þ100 parts per million (ppm) F water, CaþFþ ; LCD þ 100 ppm F water, Ca2Fþ. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Caþ Fþ and Ca2Fþ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca2Fþ. Reduced serum 25-hydroxy-vitamin D 3 , increased 1,25-dihydroxy-vitamin D 3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca2 F2 and Ca2Fþ. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca2 Fþ/Caþ F2 and Ca2Fþ /Caþ Fþ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Caþ Fþ/Caþ Fþ and Ca2Fþ /Caþ Fþ ) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.Key words: Chronic fluoride toxicity: Rats: Low calcium: Calcium homeostasis Chronic fluoride (F) toxicity is caused due to exposure to excess F . 1·5 parts per million (ppm) (1) , mainly through water and is endemic in twenty-five countries across the globe. In India, F endemicity has been reported in 196 districts of nineteen states and is considered as a public health problem (2) . Chronic F toxicity is categorised as dental, skeletal and non-skeletal fluorosis, based on the tissue affected. The very first sign of chronic F toxicity is exhibited by teeth, i.e. dental mottling, called dental fluorosis (3) . Skeletal fluorosis progresses in a slow manner and, therefore, is not clinically visible in its initial phase. Clinical symptoms of skeletal fluorosis include restricted movements of joints, stiffness and deformities of the spine such as kyphosis, bony exostoses and paraplegia due to spinal compression (4) . Non-skeletal fluorosis affects tissues other than the dental and skeletal system such as the gastrointestinal tract, brain, muscle, etc. Any kind of manifestation in these organs of inhabitants of fluorotic areas may indicate non-skeletal fluorosis (3) . Apart from these well-defined clinical symptoms, reduced food intake and body weight gain (BWG) have been observed in F-fed animals (5 -8) . However, other studies did not show any difference in BWG (9) in F-fed animals. The rea...

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