Regeneration of β-cells and neogenesis from small ducts or acinar cells promote recovery of endocrine pancreatic function in alloxan-treated rats

• Published in: Archives of medical research Vol. 35; no. 2; pp. 114 - 120
• Main Authors: De Haro-Hernández, Roberto, Cabrera-Muñoz, Lourdes, Méndez, José D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2004
• Subjects: Alloxan; Alloxan - pharmacology; Animals; Blood Glucose - metabolism; Body Weight; Bromodeoxyuridine - pharmacology; Cell Differentiation; Cholesterol - blood; Coloring Agents - pharmacology; Ductal cells; Immunohistochemistry; Islets of Langerhans - cytology; Islets of Langerhans - physiology; Male; Neogenesis; Pancreas - metabolism; Rat; Rats; Rats, Sprague-Dawley; Regeneration; Time Factors; Triglycerides - blood; β-cell; Alloxan; Regeneration; Ductal cells; Neogenesis; Rat; β-cell
• ISSN: 0188-4409; 1873-5487
• DOI: 10.1016/j.arcmed.2003.10.001

We previously showed by using biochemical parameters that male Sprague-Dawley rats receiving a single intraperitoneal (i.p.) administration of alloxan (120 mg/kg body weight) with no further treatment recovered endocrine pancreatic function after 12 days. Male Sprague-Dawley rats received an i.p. injection of alloxan (120 mg/kg body wt), were killed at 3, 6, 9, or 12 days ( n = 7), and their capacity to recover endocrine function was evaluated by means of a) biochemical parameters, which included glucose, triglyceride, and total cholesterol measurements and b) nuclear incorporation of 5′-bromodeoxyuridine (BrdU) by β and acinar cells as well as presence of neogenesis from either ductal or acinar cells using double-staining BrdU-insulin immunohistochemical technique. Three days after receiving a single i.p. administration of alloxan, rats showed increase in serum glucose, triglyceride, and total cholesterol concentrations, reaching levels of 542.4±63.1, 907.6±154.9, and 106.0±2.7 mg/dL (mean±standard deviation [SD]), respectively. At this time, increase in β-cell replication was also observed, although this reached maximum by day 6 ( p <0.001). Replication was also present in acinar cells, but these cells showed their maximum at day 3 ( p <0.001) and subsequently decreased, as did β-cells, almost steadily to normal values by day 12. Neogenesis of β-cells was observed mainly as transdifferentiation from acinar cells at day 3 and from ductal cells at day 6, after which it tended to be normal. Male Sprague-Dawley rats receiving a single i.p. alloxan dose tended to normalize their endocrine function by day 12 after alloxan administration. This process included both regeneration and neogenesis of pancreatic β-cells from either ductal or acinar cells.