INS and obesity due to melanocortin 4 receptor deficiency: Another study also found that DIRKO mice had reduced insulin secretion but enhanced insulin action and that these mice were protected from high-fat diet-induced obesity and insulin resistance further supporting the notion that incretin hormone action may negatively regulate nutrient catabolism.337 Interestingly, wild-type mice exhibited hyperglycemia and hyperinsulinemia in response to high-fat feeding but this was not observed in DIRKO mice.