New Insights Into Glucose Regulation

This review article describes the regulation of glucose homeostasis insubjects with and without diabetes based on the emergence of new informationand discusses modes of action, attributes, and limitations of current diabetestherapies. In normal physiology, glucose homeostasis is tightly controlled bythe interaction of pancreatic and gut hormones. Since the 1920s, diabetes hasbeen viewed as a disease caused by deficient secretion of insulin, resultingin reduced glucose uptake and subsequent hyperglycemia. The discovery in the1950s of the pancreatic hormone glucagon, which opposes insulin by increasingglucose appearance in the circulation, resulted in a bihormonal model ofglucose homeostasis. More recently, with the discovery of the incretinhormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropicpeptide (GIP) in the 1970s and the pancreatic hormone amylin in the 1980s, itis now understood that several organs and hormones play roles in maintainingglucose homeostasis. Therapies for diabetes have focused on compensation fordeficient insulin action through stimulation of insulin secretion,administration of insulin itself, reduction of peripheral insulin resistance,or decreased glucose absorption from the intestine. The discoveries of amylinand GLP-1 have furthered our understanding of the abnormalities involved indiabetes, enabling the development of additional therapeutic options.