Physiological, biochemical and structural analysis. The figure shows anthropometric measurements such as (a) body weights and (b) pancreatic tissue weights; metabolic measurements such as (c) plasma insulin, (d) insulin resistance indices (HOMA-IR), (e) QUICKI, and (f) global oxidative stress levels by plasma TBARS. Histological studies of H&E stained pancreata revealed hypertrophied islets with irregular morphology (black arrows) and increased vascular supply (white arrow head) with widened intraislet connective tissue septa (black arrow head) seen more with Mutants and with age compared to their Lean, and Control phenotypes. Insight shows the intrapancreatic tissue fat infiltration with age (g). These islets among Mutant phenotypes also demonstrated β-cell vacuolation (black bold circles) in the islet region compared to that from Lean and Control (h). All images were captured using ACT2U software (Nikon, Japan) attached to Nikon TE2000S Microscope (Nikon, Japan) at magnification of 200x (g) and 400x (h). Islet size was quantified using ACT2U software (Nikon, Japan) and represented graphically as Mean ± SE (n = 6) among Mutant, Lean, and Control with age (i). Mutants showed an increase in islet size and correlated well with increased tissue insulin (j) and oxidative stress (k) compared to Lean and Control and with age. Figure 1 also depicts histological comparison between the pancreatic islets between 24-month-old Control rats and 12-month-old Mutant rats showing hypertrophied islets with irregular morphology, increased vascular supply with widened intraislet connective tissue septa, intrapancreatic tissue fat infiltration, and β-cell vacuolation. Parameters such as body weight, pancreatic weight, FBG, FPI, and islet size of 24-month-old Control rats have also been indicated (m). An asterisk (*) represents significance (P < 0.05 by ANOVA) compared to Control and ($) indicates significance (P < 0.05 by ANOVA) compared to the same phenotype at 1 month.