title: Impaired pancreatic duct-cell growth in focal areas of regeneration after partial pancreatectomy in the adult Goto-Kakizaki rat, a spontaneous model of non-insulin dependent diabetes mellitus.
abstract: The Paris colony of adult Goto-Kakizaki (GK/Par) rat, a genetic model of non-insulin dependent diabetes mellitus, is characterized by a restriction of the beta-cell mass and reduced beta-cell regeneration capacity. In order to have a better understanding of the impaired mechanism(s) leading to reduced beta-cell plasticity in the GK/Par rat, we have investigated duct-cell growth capacity following 90% pancreatectomy, a well-defined procedure leading in non-diabetic rats, to sequential duct proliferation and subsequent differentiation. To this aim, we have performed pancreatectomy in 8-10-week-old male normoglycaemic Wistar and diabetic GK rats. Duct-cell proliferation and apoptosis were evaluated at different time points: day 0 (D0), day 2 (D2), day 7 (D7) and day 14 (D14) after pancreatectomy. A transient wave of duct-cell proliferation was observed on D2 in both small and main ducts in the pancreatectomized Wistar rats. A similar increase occurred in the similarly treated GK rats, but to a higher extent as compared to the Wistar rats. Thereafter, duct-cell proliferation from main or small ducts returned to non-pancreatectomized values on D7 and remained at this level on D14 in both the Wistar and GK pancreatectomized groups. In the common pancreatic duct, the number of proliferative duct-cells was higher in GK rats compared to Wistar on D0. In both the operated Wistar and GK rats, duct-cell proliferation from the common pancreatic duct similarly decreased on D2. On D7 and D14, the same parameter returned to non-pancreatectomized values in the Wistar rats, while it was maintained lower in the GK rats as compared to the GK values on D0. In focal areas of regeneration, duct-cell proliferation was significantly lower in the pancreatectomized GK group compared to the age-related Wistar group on D7 (Wistar: 5.85+/-0.98%, GK: 3.02+/-0.69%; p < 0.01) and D14 (Wistar: 3.82+/-0.29%, GK: 2.62+/-0.27%; ns). Only a few apoptotic duct-cells were observed, with no difference between the Wistar and GK groups, and that whatever the time after pancreatectomy and the duct category. Together, these results suggest that in the adult hyperglycaemic GK/Par rat facing pancreatectomy, duct-cell proliferation and apoptosis from the common pancreatic duct, main ducts and small ducts were not impaired compared to the Wistar rat. However, reduced duct-cell proliferation capacity in focal areas of regeneration in the treated GK rats probably contributes to the lower beta-cell neogenesis potential previously observed in this model.
authors.affiliation: Laboratory of the Physiopathology of Nutrition, CNRS ESA 7059, Université Paris 7/Denis Diderot, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Plachot
authors.forename: B
authors.initials: B
authors.lastname: Portha
mesh_terms: D000818:Animals; D000963:Antimetabolites; D017209:Apoptosis / Q000502:physiology; D001973:Bromodeoxyuridine; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000473:pathology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*
chemical_list: D000963:Antimetabolites; D001973:Bromodeoxyuridine