Expression of the Na(+)/l(- )symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

BACKGROUND: The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I(-)) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. METHODS: Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. RESULTS: Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. CONCLUSION: That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease

Steroid Diabetes in the Guinea Pig: Studies on Islet-cell Ultrastructure and Regeneration

Guinea pigs were maintained hyperglycemic and glucosuric by daily subcutaneous injections of prednisolone suspension. The stimulated beta cells showed de granulation, increased density of rough endoplasmic reticulum and expanded elaborate Golgi complexes. Glycogen particles accumulated progressively in these cells until by the third month glycogen aggregates encroached on large areas of the cytoplasm. By the fourth and fifth month many beta cells appeared as small bags filled with glycogen. Cytoplasmic remnants in these glyco gen-filled beta cells showed organelles of normal appearance. Beta cells proliferated during the first two months as evaluated by the proportion of beta cells incorporating 3H-thymidine. In guinea pigs killed after threeand four months of prednisolone treatment the 3H-thymidine index declined to levels found in untreated guinea pigs.</jats:p

Persisting Enhanced Proinsulin-insulin and Protein Biosynthesis (3H-Leucine Incorporation) by Pancreatic Islets of the Rat after Glucose Exposure

Pancreatic islets isolated from rats infused with glucose for twenty-four hours incorporated 3H-leucine into protein at higher rates than islets isolated from normoglycemic rats. Incorporation into proinsulin-insulin showed a thirteenfold increase. The effect on other islet proteins was fourfold. Exposure of islets from normoglycemic rats to high glucose in vitro for twenty and ninety minutes and subsequent incubation with 3H-leucine at low glucose showed a twofold and fivefold increase in proinsulin biosynthesis. In the in vitro system pre-exposure of the islets to mannose and dibutyryl-cyclic AMP induced a much smaller increase in proinsulin biosynthesis.</jats:p

Secretion of Insulin in a Perifusion System and Conversion of Proinsulin to Insulin by Pancreatic Islets from Hyperglycemic Rats

The secretory pattern of insulin and the rate of conversion of proinsulin to insulin were studied in isolated pancreatic islets from normoglycemic (buffer-infused for 24 hours) and hyperglycemie (glucose-infused for 24 hours) rats. The profiles of insulin secretion obtained during one hour of perifusion were markedly different in the two groups. The rate of insulin secretion by islets from the hyperglycemie rats was initially very high but progressively declined during the late period of the perifusion. The reverse pattern was found with the islets from buffer-infused rats. For the estimation of the rate of proinsulin to insulin conversion, islets were pulse-labeled with L-[4,5-3H]-leucine for 15 minutes and “chase”-incubated for 30 and 60 minutes. Labeled rat proinsulins and rat insulins in the medium and in the islet extracts were separated by a validated SDS-urea electrophoretic acrylamide procedure following immunoprecipitation. The conversion rate was estimated from the radioactivity in the insulin band, expressed as a per cent of the radioactivity in the proinsulin + insulin bands. Islets from hyperglycemie rats converted newly synthesized proinsulin to insulin at significantly higher rates than did control islets.</jats:p

Streptozotocin Diabetes in the Mouse and Guinea Pig

A single injection of streptozotocin into mice produced an extensive necrosis of the beta cells resulting in permanent diabetes. The histological changes in the islets were similar to those described after the injection of alloxan. The regenerative capacity of beta cells which survived the cytotoxic injury was limited. Hypoglycemia induced by an injection of insulin or hyperglycemia induced by glucose injections sensitized the beta cells to streptozotocin. In contrast, injection of insulin antibody effectively protected the beta cells from the cytotoxic injury. Streptozotocin caused widespread necrosis of the beta cells of the guinea pig and the obese hyperglycemic mouse. Both these species had proven resistant to the diabetogenic effect of alloxan. Diabetic guinea pigs were observed for eight months, without reversion of the diabetic syndrome.</jats:p