Incretin: any gut hormone associated with food intake-stimulation of insulin secretion from the pancreas
Glucose-stimulated insulin secretion, GSIS: process of glucose uptake and metabolism by β-cells leading to increased ATP production which inhibits a potassium-dependent ATP (KATP) channel resulting in depolarization of the membrane triggering calcium influx and insulin secretory vesicle fusion with plasma membrane
ABCC8/KCNJ11: ATP-binding cassette, subfamily C, member 8 (ABCC8-encoded protein is also known as the sulfonylurea receptor, SUR) and potassium inwardly rectifying channel, subfamily J, member 11, protein components of the KATP channel of β-cells that regulates insulin secretion
TCF7L2: transcription factor 7-like 2, T-cell–specific HMG-box, involved in Wnt signal transduction, polymorphisms in this gene are the most highly correlated with potential for development of T2D
Insulin resistance, IR: a phenomenon whereby binding of insulin to its receptor results in impaired or failed propagation of normal signal transduction events
Insulin was one of the first identified pancreatic hormones. It is secreted by the β-cells of the pancreas and directly infused, via the portal vein, to the liver where it exerts profound metabolic effects. Its major function as a pancreatic hormone is to counter the concerted action of a number of hyperglycemia-generating hormones and to maintain low blood glucose levels, particularly in response to food consumption. In addition to its role in regulating glucose homeostasis, insulin stimulates lipogenesis, diminishes lipolysis, and increases amino acid transport into cells. Because there are numerous hyperglycemic hormones, untreated disorders associated with insulin generally lead to severe hyperglycemia and shortened life span as is typically seen in poorly controlled type 2 diabetes, T2D (see Chapter 47).
Insulin also exerts activities typically associated with growth factors (Figure 46-1). Insulin is a member of a family of structurally and functionally similar molecules that includes the insulin-like growth factors (IGF-1 and IGF-2), and relaxin. The tertiary structure of all 4 molecules is similar, and all have growth-promoting activities. Insulin modulates transcription and stimulates protein translocation, cell growth, DNA synthesis, and cell replication, effects that it holds in common with the insulin-like growth factors and relaxin.
Multiple roles of insulin. When insulin binds to its receptor it triggers receptor autophosphorylation that in turn triggers the activation of a wide array of signal transducing proteins (highly simplified in this figure). The end results of insulin receptor activation are varied and in many cases cell-type specific but includes alterations in metabolism, ion fluxes, protein translocation, transcription rates, and growth properties of responsive cells. Protein abbreviations are described throughout the text. Reproduced with permission of the medical biochemistry page, LLC.
The Insulin Receptor and Signaling
All of the effects of insulin are the result of the activation of the insulin receptor. The insulin receptor belongs to the class of cell surface receptors that exhibit intrinsic tyrosine ...