The patterns of beta-cell regeneration in untreated diabetic and insulin-treated diabetic Syrian hamsters after streptozotocin treatment.
Our previous study showed that Syrian hamsters recover from streptozotocin (SZ)-induced diabetes spontaneously and that insulin therapy adversely affects diabetes. The recovery and lack of recovery was associated with beta-cell regeneration and lack of regeneration. In this study, we examined the patterns of beta-cell regeneration in hamsters by using an immunohistochemical-autoradiographical method. We used tritiated thymidine to examine the DNA synthesis in islet cells and evaluated the number of labeled cells that were or were not immunoreactive with antiinsulin, antiglucagon, and anatisomatostatin. The results showed that, in untreated control hamsters, beta-cell regeneration took place both from preexisting beta cells and from undifferentiated cells (labeled cells unstained with any of the three antibodies) in equal proportions. In the SZ-treated hamsters, however, most regenerating cells seemed to derive from undifferentiated cells within the islets. Insulin therapy inhibited beta-cell regeneration from both the preexisting cells, but more so from the undifferentiated cells. The number of extrainsular islet cell foci was the same in all treatment groups and paralleled the number of islets in each animal during the entire experiment. We concluded the following about diabetic hamsters: 1. beta-Cell regeneration occurs primarily from undifferentiated cells within the islet; 2. Exogenous insulin inhibits beta-cell differentiation from the precursor cells; and 3. The response of intrainsular and extrainsular islet cells to SZ and insulin therapy is similar and the number of extrainsular islet cell foci per pancreas parallel the changes in the number of islets.
Tomioka
T
T
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 61898.
Fujii
H
H
Hirota
M
M
Ueno
K
K
Pour
P M
PM
D000818:Animals; D000906:Antibodies; D001345:Autoradiography; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005934:Glucagon / Q000032:analysis; D007150:Immunohistochemistry; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D012038:Regeneration; D013004:Somatostatin / Q000032:analysis; D013194:Staining and Labeling; D013311:Streptozocin; D013936:Thymidine / Q000378:metabolism
D000906:Antibodies; D007328:Insulin; D013004:Somatostatin; D013311:Streptozocin; D004247:DNA; D005934:Glucagon; D013936:Thymidine