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BERNARD PORTHA  AN. R. ACAD. NAC. FARM.

   FIGURE 1. Design for the production of spontaneously diabetic GK rat by
repetition of selective phenotyping: here is shown the distribution of the sum of

      blood glucose values (S blood glucose) during a standardised oral glucose
 tolerance test (OGTT) in original parent Wistar rats and F1 to F35 rats. The GK
  rat line (Wistar strain) has been produced by Goto et al. in Tohoku University,
  Sendaï, Japan, by selective breeding over many generations from a non diabetic
 Wistar rat colony on the basis of glucose intolerance (12). The diabetic state was

         reported to become stable after the 30 generations of selective crosses.

from all colonies have been found similar or somewhat increased as
compared to age-matched controls. During the long-term inbreeding
of GK rats (> 20 years) the animals have maintained rather stable
levels of glucose intolerance and impairment of glucose-induced
insulin response, also when studied in the various sublines of GK rats.
However, other characteristics such as beta cell number, insulin
content and islet metabolism have been reported to differ between
different subline colonies, suggesting that different local breeding
environment and/or newly introduced genetic changes account for
contrasting phenotypic properties, but it is not clear wether the
reported differences are artefactual or true. Signs of early neuropathy
(2 mo) have been reported in GK adult while nephropathy and
retinopathy develop late (12 mo). The VMH-lesioned GK rat displays
accentuated hyperglycaemia and hypertriglyceridaemia with visceral

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