title: Insulin resistance or hypersecretion? The βIG picture revisited.
abstract: Mathematical models of glucose, insulin and pancreatic beta-cell mass dynamics are essential to our understanding of the physiological basis of the development of type 2 diabetes. The classical view of diabetes is that the disease develops due to insulin insufficiency. An alternate viewpoint that has recently staged a revival is that diabetogenesis is a hypersecretion disorder. A prominent model of diabetes progression is the βIG model due to Topp and coworkers. Here we study two new variants of the Topp model, which we name "Topp-IR" and "Topp-HS". Topp-IR is a model in which increasing insulin resistance is sufficient to drive a system away from health towards hyperglycemia. Topp-HS describes the hypersecretion model in mathematical terms. We thus show that the hypersecretion hypothesis is theoretically sound, and is therefore a potential route to diabetes. On the basis of insights derived from modeling, we clarify several subtleties of that argument, including postulating a central role for transient insulin peaks in driving insulin resistance.
authors: Mathematics and Biology, IISER Pune, Pune, India. Electronic address: pranay.goel@gmail.com.
authors: Pranay
authors: P
authors: Goel
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008954:Models, Biological
chemical_list: D007328:Insulin
keywords: Theories of diabetogenesis; Type 2 diabetes