Stable and functional regeneration of pancreatic beta-cell population in nSTZ-rats treated with tungstate

• Published in: Diabetologia Vol. 47; no. 3; pp. 470 - 477
• Main Authors: FERNANDEZ-ALVAREZ, J, BARBERA, A, NADAL, B, BARCELO-BATLLORI, S, PIQUER, S, CLARET, M, GUINOVART, J. J, GOMIS, R
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.03.2004; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Diabetes; Diabetes Mellitus, Experimental - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Glucagon; Glucose; Health care; Insulin; Islets of Langerhans - drug effects; Islets of Langerhans - pathology; Islets of Langerhans - physiology; Laboratory animals; Medical sciences; Organ Size - drug effects; Pancreas; Pancreas - anatomy & histology; Pancreas - drug effects; Rats; Rats, Wistar; Regeneration - drug effects; Regeneration - physiology; Tungsten Compounds - pharmacology; France; United States > US; Spain; Endocrinopathy; Pancreatic hormone; Pancreatic duodenal homeobox-1; Rat; Diabetes mellitus; Rodentia; Neogenesis; Tungstates; Insulin; Tungstate; Regeneration; Vertebrata; Mammalia; Insulin-like agents; Animal; Beta cell; Pancreas
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-004-1332-8

Sodium tungstate has recently emerged as an effective oral treatment for diabetes. We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential. Sodium tungstate was administered via drinking water to healthy and neonatal streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was removed and morphometric and immunocytochemical studies were carried out. The molecular mechanism of tungstate's action was also studied. In nSTZ rats administration of this compound normalised glycaemia, and increased insulinaemia and islet insulin content. Blood glucose concentrations were normalised as early as on day 4 of treatment, and tungstate treatment produced a partial recovery of beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal. Morphometric studies showed that the increase in beta-cell mass was not due to beta-cell hypertrophy but to hyperplasia, with an increase in islet density in treated diabetic rats. Tungstate treatment increased extra-islet beta-cell replication without modifying intra-islet beta-cell replication rates. Moreover, the treatment induced increases in insulin-positive cells located close to ducts; and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active neogenesis. In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38. These observations indicate that tungstate treatment is able to regenerate a stable, functional pancreatic beta-cell population which leads to and maintains normoglycaemia.