Deletion of glucose transporter GLUT8 in mice increases locomotor activity.

Transport of glucose into neuronal cells is predominantly mediated by the glucose transporters GLUT1 and GLUT3. In addition, GLUT8 is expressed in some regions of the brain. By in situ hybridization we detected GLUT8-mRNA in hippocampus, thalamus, and cortex. However, its cellular and physiological function is still unknown. Thus, GLUT8 knockout (Slc2a8 -/-) mice were used for a screening approach in the modified hole board (mHB) behavioral test to analyze the role of GLUT8 in the central nervous system. Slc2a8 -/- mice showed increased mean velocity, total distance traveled and performed more turns in the mHB test. This hyperactivity of Slc2a8 -/- mice was confirmed by monitoring locomotor activity in the home cage and voluntary activity in a running wheel. In addition, Slc2a8 -/- mice showed increased arousal as indicated by elevated defecation, reduced latency to the first defecation and a tendency to altered grooming. Furthermore, the mHB test gave evidence that Slc2a8 -/- mice exhibit a reduced risk assessment because they performed less rearings in an unprotected area and showed significantly reduced latency to stretched body posture. Our data suggest that behavioral alterations of Slc2a8 -/- mice are due to dysfunctions in neuronal processes presumably as a consequence of defects in the glucose metabolism.

Mouse GLUT8: genomic organization and regulation of expression in 3T3-L1 adipocytes by glucose.

Glucose transporter 8 (GLUT8) is a class III sugar transport facilitator predominantly expressed in testis and insulin-regulated tissues. Here we describe its genomic organization, the identification of its promoter region, and the regulation of its expression in 3T3-L1 cells. The mouse Glut8 gene spans approximately 9 kb, consists of 10 exons, and is highly similar to the human GLUT6 gene. Its 5'-flanking region exhibits promoter activity when fused with a luciferase reporter construct and expressed in HEK-293T cells. A deletion analysis indicated that the critical promoter elements are located in a region between -381 and the transcription start. This region comprises a CAAT box and consensus binding sites for the transcription factors SRY and NF1 that were highly conserved in the mouse and in the human sequence. In 3T3-L1 cells, GLUT8 mRNA levels increased markedly during the differentiation of cells. In contrast to GLUT1, expression of GLUT8 mRNA was significantly reduced by glucose deprivation and by prolonged hypoxia. The present data suggest that the function of GLUT8 is related to the adipocyte-like phenotype of 3T3-L1 cells, and that its expression is controlled by the metabolism of the adipocyte.

Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle.

Human GLUT11 (encoded by the solute carrier 2A11 gene, SLC2A11) is a novel sugar transporter which exhibits significant sequence similarity with the members of the GLUT family. The amino acid sequence deduced from its cDNAs predicts 12 putative membrane-spanning helices and all the motifs (sugar-transporter signatures) that have previously been shown to be essential for sugar-transport activity. The closest relative of GLUT11 is the fructose transporter GLUT5 (sharing 41.7% amino acid identity with GLUT11). The human GLUT11 gene (SLC2A11) consists of 12 exons and is located on chromosome 22q11.2. In human tissues, a 7.2 kb transcript of GLUT11 was detected exclusively in heart and skeletal muscle. Transfection of COS-7 cells with GLUT11 cDNA significantly increased the glucose-transport activity reconstituted from membrane extracts as well as the specific binding of the sugar-transporter ligand cytochalasin B. In contrast to that of GLUT4, the glucose-transport activity of GLUT11 was markedly inhibited by fructose. It is concluded that GLUT11 is a novel, muscle-specific transport facilitator that is a member of the extended GLUT family of sugar/polyol-transport facilitators.

Chronic inositol increases striatal D(2) receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder.

A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT(2) and D(2) receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density. This suggests that D(2) receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT(2) receptor in this response is questionable.

Correlation of oral surface temperatures and the lesions of leprosy.

A short review of the literature on the optimum temperature for the growth of Mycobacterium leprae is followed by a report of an investigation into the correlation of oral surface temperatures with oral leprous lesions. It is concluded that the oral lesions of leprosy occur more frequently in areas of the mouth with a lower surface temperature.

The role of angiography in facial trauma: a case report.

Angiography is a useful diagnostic tool in maxillofacial trauma. An important indication for its use is in establishing the proximity of foreign objects to the arterial supply to the head and neck. An unusual case of a deeply penetrating knife wound of the face is described to illustrate this point.

Oral manifestations of leprosy.

A total of 37 out of 187 patients with leprosy had oral lesions. All were biopsied. Oral lesions were found most frequently in patients with lepromatous leprosy. Prevalence of oral lesions was higher in males than in females (73%:27%). Oral lesions were recorded on the WHO topographical map, and in most cases (92%) several topographical locations were affected, including hard palate in all cases. Topographical locations affected increase with age; males are more extensively affected than females (p = 0.001); and patients with oral lesions who reported affected family members (11 out of 37) had more extensive oral lesions than those who did not. In 27 cases with oral lesions histopathological diagnosis was possible.

Erythema nodosum leprosum: a possible cause of oral destruction in leprosy.

Apart from vague statements and speculative remarks, the role of ENL in the oral cavity has not been considered in the recent English language literature. A case of oral ENL is reported, and we postulate that ENL plays a prominent role in the intra-oral destruction noted in leprosy. Information gathered from the literature and from our own experience with a series of 37 leprosy patients with oral lesions support this postulation.

Disseminated histoplasmosis: aspects of oral diagnosis.

This paper reports two cases of histoplasmosis in Natal: histoplasmosis is a granulomatous mycosis caused by H. capsulatum. The Indian mynah may possibly have a rôle in the epidemiology of this disease. In-vitro culture of the organism is the definitive step in confirming the diagnosis of histoplasmosis. The overgrowth of contaminants often precludes culturing; but a clinical regimen of topical antifungal agent and mouthwash may improve the chances of culturing H. capsulatum.

Tuberous sclerosis: report of a case with fibromatosis of the facial soft tissues.

Tuberous Sclerosis (TS) is a dominantly inherited disorder which is characterised by a triad of mental deficiency, epilepsy and angiofibromas of the face. Sub- and periungual fibromas, shagreen patches usually found in the lumbosacral region and hypopigmented skin lesions are less often seen. Paraventricular calcifications, skeletal disorders and rarely, ophthalmic tumours are also described. Oral manifestations include whitish confluent nodules on the mucosa, enamel hypoplasia, mandibular cysts, and oral fibromas. A case of fibromatosis of the subcutaneous tissue overlying the angle of the mandible is described together with TS. To the best knowledge of the authors, this is the first such case reported in the literature.