Table 1. Studies that have observed accumulation of misfolded hIAPP in T2DM patients in comparison to healthy controls.

Tissue/organ	Methods used	Observations	Reference
Blood	Western blotting and ELISA	Monomers in plasma, white blood cells and red blood cells. hIAPP-coated RBCs show reduced functional haemoglobin and have lower deformability	[44]
Blood	Western blotting, TEM, CD	Soluble oligomers in the form of homooligomers (trimers, hexamers, dodecamers) and heterooligomers varying in size (1–400 nm) from sera of children with T1DM and T2DM and obese children. Fibrils 55–252 nm in length present in T2DM and obese patients	[45]
Blood	Immunochemistry with anti-IAPP antibodies, Congo Red staining	hIAPP plaques, amyloid fibrils found in the blood vessel walls and also perivascular spaces	[41]
Brain	Immunohistochemistry with anti-IAPP antibodies, Congo Red staining, Western blotting, ELISA, qRT-PCR	hIAPP oligomers (trimers 12 kDa, tetramers 16 kDa, and pentamers 20 kDa) and hIAPP plaques > 20 µm in diameter identified in the temporal lobe grey matter. Tetramers abundant in brain homogenates. Tissues showed increased interstitial space, vacuolation, spongiform change, and capillaries bent at hIAPP accumulation sites. hIAPP mRNA in the brain is ∼104 lower than in the pancreas	[41]
Heart	Immunohistochemistry and Western blotting	Oligomers (>32 kDa), fibrillar tangles, plaques, found in diabetic and obese patients’ hearts. Small oligomers found in healthy hearts from obese patients	[40]
Kidneys	Immunohistochemistry, Immunogold staining TEM	hIAPP deposits composed of straight non-branching fibrils 12–16 nm in diameter observed in Kimmelstiel–Wilson nodules, Bowman’s capsule in patients with diabetic nephropathy	[39]
Pancreas	Immunohistochemistry with anti-IAPP antibodies, qRT-PCR	Fibrillar deposits in pancreatic islets	[41]
Pancreas	Congo Red staining	Fibrillar deposits in pancreatic islets adjacent to the islet cells	[46]
Pancreas	Peroxidase-antiperoxidase staining, Immunohistochemistry, Congo Red staining	Amyloid deposits plus amorphous deposits stained with Congo Red in Islets of Langerhans. Amyloid did not stain with anti-insulin antiserum	[18]
Pancreas	Congo Red staining	Amyloid fibrils found mostly between capillaries and epithelial islet cells. Amyloid likely originated from β-cells: cells show amyloid-filled invagination and orientation of hIAPP fibrils were seen perpendicular to cell surface. Enlarged macrophages with amyloid deposits. β-cells degraded in the islets	[47]
Pancreas	Microscopy staining with Haematoxylin, Eosin, Picric acid stain	Deposition of ‘hyaline material’ in pancreatic parenchymal cells and immediately outside the walls of the capillaries	[12]

Summarised here are the location of the misfolded hIAPP, the morphology of the misfolded forms, and experimental techniques used to analyse the misfolded aggregates from tissues acquired post mortem. Abbreviations: CD, circular dichroism; ELISA, enzyme-linked immunosorbent assay; qRT-PCR, quantitative real-time polymerase chain reaction; TEM, transmission electron microscopy.