We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia.
Previously we demonstrated that NEU1 activates the insulin receptor (IR) and that NEU1-deficient CathA<sup>S190A-Neo</sup> mice (hypomorph of the NEU1 activator protein, cathepsin A/CathA) on a high-fat diet (HFD) develop hyperglycaemia and insulin resistance faster than wild-type animals.
Acute induction of insulin receptor knockout in adipocytes changed the substrate preference to fat before induction of a diabetic phenotype including hyperinsulinaemia and hyperglycaemia.
Non-peptidyl small molecule, adenosine, 5'-Se-methyl-5'-seleno-, 2',3'-diacetate, activates insulin receptor and attenuates hyperglycemia in type 2 diabetic Lepr<sup>db/db</sup> mice.