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

Arch Med Res. Mar-Apr 2004;35(2):114-20. doi: 10.1016/j.arcmed.2003.10.001.

Abstract

Background: 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.

Methods: 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 beta and acinar cells as well as presence of neogenesis from either ductal or acinar cells using double-staining BrdU-insulin immunohistochemical technique.

Results: 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 beta-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 beta-cells, almost steadily to normal values by day 12. Neogenesis of beta-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.

Conclusions: 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 beta-cells from either ductal or acinar cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloxan / pharmacology*
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Bromodeoxyuridine / pharmacology
  • Cell Differentiation
  • Cholesterol / blood
  • Coloring Agents / pharmacology
  • Immunohistochemistry
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / physiology*
  • Male
  • Pancreas / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration
  • Time Factors
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Coloring Agents
  • Triglycerides
  • Alloxan
  • Cholesterol
  • Bromodeoxyuridine