Insulin resistance, the most important pathophysiological feature in various prediabetic and diabetic states is partly related to impaired glucose-stimulated insulin secretion and insulin modulation of pancreatic beta cell with peripheral impaired insulin response. This chapter concentrates on aspects of potential new strategies in the treatment of the disease going from nutritional preventive approaches towards currently utilized drugs for treatment that target the pancreatic beta cells with potentiation of glucose-stimulated insulin secretion.