Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass
Figure 1
From the nondiabetic Wistar rat to the spontaneously diabetic GK (Goto-Kakizaki) rat. The inbred GK rat line (Wistar strain) was produced by Goto et al. at Tohoku University, Sendaï, Japan, by selective breeding of normal Wistar rats over many generations using glucose tolerance value (and not basal glucose value only) as a discriminant phenotype [23]. Only W rats selected at the upper limit of normal distribution for glucose tolerance were used. The diabetic state (basal hyperglycemia) was reported to become stable after the 30 generations of selective crosses in the original Japanese colony. Here is illustrated the distribution of the sum of blood glucose values ( ) during standardised oral glucose tolerance tests (OGTTs) performed in original parent Wistar rats, in rats from generations F1 to F35 in the original Japanese colony and in rats from generations F35 to F120 bred under our conditions in Paris from 1989 until now (subline GK/Par). In the inbred GK/Par rat line, all rats are nonoverweight, nonketotic, and display moderate fasting hyperglycemia with strong postprandial glucose intolerance. No attenuation, nor aggravation, of the diabetic phenotype overtime (more than 20 years and 80 generations) was registered in the GK/Par line.
