TABLE 1.

Akita insulin mutant mice exhibit β-cell hyperplasia during early progression to diabetes

Genotype	Ins2+/+	Ins2+/Akita	Ins2+/Akita
	Perk+/− and +/+	Perk+/− and +/+	βPerk+Perk+/− and +/+
Blood glucose (mg/dl)	136.0	244.1*	297.8†
Average number β-cells per islet	29.6	68.7‡	35.4 (NS)
Percent TUNEL+ β-cells	0.37	0.04	0.09
Chop mRNA	100.0 ± 42.7	146.7 ± 48.8 (NS)	150.0 ± 49.4 (NS)

The data shown in this table is representative of mice that belong to the postnatal age group p14–17. Serum blood glucose was determined in random fed mice. To estimate β-cell mass and cell death, tissue sections were immunostained for insulin, TUNEL, and DAPI. β-Cells and insulin-positive cells were manually counted for all islets containing more than five β-cells. The average number of β-cells within a cross-section of each islet was calculated. To estimate β-cell death, cells that were insulin and TUNEL positive were manually counted. For IHC analysis, pancreata were harvested from littermates. The number of mice, islets, and β-cells counted were as follows: Ins2^+/ Perk^+/− and ^+/+, mice = 6, islets = 136, and β-cells = 2,172; Ins2^+/Akita Perk^+/− and ^+/+, mice = 10, islets = 277, and β-cells = 12,777; and Ins2^+/Akita; βPerk⁺ Perk^+/− and ^+/+, mice = 6, islets = 136, and β-cells = 3,492. Chop mRNA level for each genotype was normalized to Ins2^+/+; Perk^+/− and P^+/+. For Chop mRNA, islets were isolated from littermates (Ins2^+/+; Perk^+/− and ^+/+, n = 6; Ins2^+/Akita; Perk^+/− and ^+/+, n = 2; Ins2^+/Akita; βPerk⁺ Perk^+/− and ^+/+, n = 4). Comparison of means (Student t test) showed no significant differences between any of the paired comparisons for Chop mRNA levels.

*P = 0.055;

†P = 0.0066;

‡P = 0.00,016 vs. age-matched controls (Ins2^+/+; Perk^+/− and ^+/+). NS, not significant.