Figure 1

The HIP rat: a “humanized” animal model of hyperamylinemia. A – Specificity of human amylin RNA expression in the pancreas in HIP rats documented by qRT-PCR. Human pancreas was used as positive control for human amylin mRNA, while WT rat brain and pancreas were negative controls. Human amylin mRNA in the HIP rat brain is below the limit of detection (red line indicating that the signal measured in the qRT-PCR experiment was greater than 35 CT). Note also the logarithmic scale and scale break. B – Blood glucose in HIP rats and WT littermates. In HIP rats, the non-fasted blood glucose increases in the 150–200 mg/dl range (pre-diabetes) by ~7-9 months of age. By 10–12 months of age, the non-fasted blood glucose rises to over 200 mg/dl and the HIP rats develop T2D. (N = 32 HIP rats, N = 15 WT littermates). C – Blood insulin in HIP rats and WT littermates. In pre-diabetic HIP rats (7–9 months old), pancreatic β-cells compensate for insulin resistance by increasing secretion of insulin (hyperinsulinemia). (N = 32 HIP rats, N = 15 WT littermates). D – Blood amylin in HIP rats and WT littermates. Parallel with hyperinsulinemia (C), HIP rats develop hyperamylinemia by 7–9 months of age. (N = 32 HIP rats, N = 15 WT littermates). E – Body weight in HIP rats and WT littermates. HIP rats and WT littermates have similar body weights before the onset of T2D. With the development of T2D, HIP rats lose weight. (N = 32 HIP rats, N = 15 WT littermates).