Regeneration of beta-cells and neogenesis from small ducts or acinar cells promote recovery of endocrine pancreatic function in alloxan-treated rats.
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.
De Haro-Hernández
Roberto
R
Unidad de Investigación Médica en Enfermedades Metabólicas, Departamento de Patología Anatómica, Hospital de Especialidades, Centro Meédico Nacional Siglo XXI (CMN-SXXI), IMSS, Mexico City, 06703 Mexico.
Cabrera-Muñoz
Lourdes
L
Méndez
José D
JD
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D002784:Cholesterol / Q000097:blood; D004396:Coloring Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004396:Coloring Agents; D014280:Triglycerides; D000496:Alloxan; D002784:Cholesterol; D001973:Bromodeoxyuridine