Islet transplantation is a promising treatment for type 2 diabetes, but its success is impaired by progressive graft loss, likely due to cytotoxic aggregation of the hormone human islet amyloid polypeptide (IAPP) secreted by the endocrine pancreas. Alternatively, the effectiveness of porcine xenotransplantations might be explained by the fibrillization-resistance of the porcine mutant. To better elucidate such molecular mechanisms, we performed comparative replica-exchange molecular dynamics simulations of both human (hIAPP) and porcine (pIAPP) isoforms. The accurate force field Charmm22* with explicit aqueous solvation TIP4P/Ew ensured a minimal structural bias around physiological temperatures. Along which, the peptides are shown to present no structural-phase transition of folding from a microcanonical thermodynamics perspective. Both IAPP isoforms predominantly exhibit random-coil structures, but in a minor percentage we observed a direct α-helix → β-sheet thermal conversion during the folding process of hIAPP, which is absent in pIAPP. The amyloidogenic segment 20-29 in pIAPP, which hosts 5 out of the 10 overall mutations found in this peptide, is strongly depleted of β-sheet structures in constrast to hIAPP. Hydrogen bond analysis revealed a predominant frequency of 3-helix contacts in this residue range for pIAPP. These features of pIAPP anticorrelate with the presence of a well-known β-sheet rich monomeric state that in hIAPP acts as an intermediate inducing oligomerization.