Studies on Rabbits from Ancestors Diabetic for Several Successive Generations, Especially on Spontaneous Occurrence of Diabetes in F₄ and F₅ Rabbits

Abstract

Male and female rabbits were made alloxan-diabetic, paired among themselves a certain time after the diabetization and the yotings begotten then were named rabbits F1. These F1 rabbits were similarly made diabetic upon attaining maturity, paired and made to breed. Such a procedure was repeated for five generations and the resulting F₁-F₅ rabbits were made the subject of our study. The results were as follows:
1. In increase of bodyweight after birth, little difference was found between the normal and the F, F5 rabbits, except that the F₃ rabbits were slightly inferior in this respect and the F₄ and F₅ rabbits somewhat better, especially around 60-120 days after birth.
2. The β-cells in the Langerhans islets in the pancreas of F rabbits were found suffering from hypoplasia. It was evidenced by the decrease both in number and in size of β-cells per islet seen on the sections, observable in all ages from 30 days downwards, and in fact this reduction of cells progressed step by step from generation to the next. For example, the number of β-cells per islet was 31.4, 27.2, 22.5, 16.0 and 13.3 and their size 163, 142, 130, 129 and 104 μ² respectively in P, F₁, F₂, F₃ and F₄ rabbits 120 days after birth.
3. The a-cells in F rabbits showed the tendency of slowly decreasing in size from generation to generation (at 120 days after birth, the respective areas showed the values of 148, 129, 126, 120, 111 μ² in P and F₁-F₄, rabbits), but their number did not change appreciably.
4. The size of Langerhans islets was always smaller in F rabbits than in normal rabbits from 30 days after birth downwards, and this reduction in size progressed from generation to generation. For example, the mean area of the islets at 120 days after birth was 79.3×, 74.2×, 68.6×, 62.8× and 47.1×100μ² respectively in P and F₁-F₄ rabbits.
We found no marked change in the number of Langerhans islets.
5. Based upon the assumption that the Langerhans islets are spherical in shape and utilizing the data of measurements of the size and the number of the islet cells and the number of islets in rabbits 120 days of age, we made a tentative calculation of the volume occupied by the cells in 1mm³ of pancreas, and have found that the total volume of β-cells per mm³ of pancreas decrease by leaps and bounds. Thus, the value stands at 82×100, 000μ³ normal rabbits but drops to 49×100, 000μ³ in F₁, to 36× in F₂, to 14× in F₃ and to 11 (or 8)× 100, 000μ³ in F₄ rabbits. In F₄ rabbits, the volume drops to about 1/8-1/10 of normal rabbits, and this value is presumed to be dangerously near or approximately equal to the threshold value of incidence of diabetes caused by injury in β-cells. The total volume of a-cells showed slight reduction but much less remarkable than that of β-cells.
6. The double charge sugar test conducted on normal and F rabbits showed that while all cases of normal, F₁ and F₂ rabbits resulted positively in Staub's effect, some F₃ and the majority of F₄ rabbits showed negative results.
7. By a continued observation of the rabbits for more than 120 days after birth, we found no spontaneous occurrence of diabetes (diabetes without giving diabetogenic reagents or taking any external means) in F₁, F₂ and F₃ rabbits, not to speak of the normal rabbits. In F4 and F5 rabbits we found sure signs of spontaneous occurrence of diabetes. 18 of the 18 F₄ rabbits and 7 of the 7 F₅ rabbits fell to diabetes, between 61 to 425 days after birth.