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VOL. 73 (3), 763-784, 2007 FROM PATHOGENESIS TO THERAPEUTIC OF TYPE 2...
fat accumulation and both microangiopathy and macroangiopathy.
Figure 2 summarizes the GK/Par rat pathogenic sequence culminating
in the chronic hyperglycaemia at adult age.
FIGURE 2. Time-course of diabetes in the GK/Par rat model. Males and
females are similarly affected and their diabetic state is stable over 72 weeks of
follow up (13). In adult GK rats, plasma insulin release in vivo in response to i.v.
glucose is abolished (13). In vitro studies of insulin release with the isolated
perfused pancreas or with perifused islets indicate that both the early and late
phases of glucose-induced insulin release are markedly affected in the adult GK
rat. Concerning insulin action in adult GK rats, decreased insulin sensitivity has
been reported in the liver, in parallel to moderate insulin resistance in extrahepatic
tissues (muscles and adipose tissues) (13). Hyperglycaemia is preceded by a period
of normoglycaemia, ranging from birth to weaning (15). Therefore during this
period the young GK rats can be considered to be prediabetic.
WHAT IS WRONG IN THE BETA-CELL POPULATION
OF THE GK/PAR RAT ONCE DIABETES IS THERE?
Decreased beta-cell number
In the adult GK/Par, total pancreatic beta-cell mass and pancreatic
insulin stores are similarly decreased (by 60%) (15). This alteration of
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