![]() ![]() Insulin and glucagon affect each other's secretion with strengths I g and G i respectively external glucose represents meals, glucose consumption represents exercise. ( b) Scheme for the intra-islet topology: green arrows represent activating interactions, red arrows are inhibitory interactions. Remote insulin promotes the uptake of glucose from the blood by muscles and bones, thus decreasing its level brain asserts a constant blood glucose consumption food represents an external source of glucose. ( a) Scheme for the blood glucose homeostasis mechanism: alpha and beta cells mediate two negative feedback loops with glucose through the liver’s glucose production. The intra-islet network and alpha and beta cell interactions. Although islet architecture, glucose response to external stimuli and, in general, metabolism, are different from species to species 9, 10, 11, 12, 13, 14, 15, the described core mechanism is considered to be common to most mammals. Co-secretion of glucagon under protein-rich, carbohydrate-poor meals is thought to counteract the simultaneous effects of insulin on blood glucose levels, thus preventing dangerous glucose drops termed “hypoglycemia” 8. This correlated secretion stems from the additional role of insulin as a stimulator of cellular consumption of metabolized amino acids. In addition to their action on blood glucose levels, glucagon and insulin are jointly secreted in response to protein intake 6, 7. ![]() Failure of beta cells to secrete insulin in diabetic patients results in uncontrolled fluctuations in blood glucose levels. Thus, insulin and glucagon actions on blood glucose levels mediate two negative feedback loops in which insulin acts as a repressor, while glucagon as activator (Fig. In contrast, glucagon instructs the liver to rapidly release glucose into the circulation when plasma glucose levels are low (i.e. meals) and brings about an immediate cessation of glucose production by the liver and a systemic uptake of glucose for storage by tissues such as the liver and muscle, thus lowering glucose to its basal state. Insulin is secreted by beta cells in response to elevated blood glucose levels (i.e. These two cell types are adjacently located in the islet of Langerhans 5. Glucose homeostasis is controlled by two antagonistic hormones, insulin and glucagon, secreted by beta and alpha cells respectively. Blood glucose levels are maintained at approximately 5 mM in humans (90 mg/ dL) 2 and rarely exceed 6.9 mM or drop below 3.8 mM 3, 4. It is a hallmark of mammalian physiology: temperature, pH, fluid volume, calcium levels and blood pressure are some examples of quantities in the body that are maintained at constant levels. Homeostasis is a specialized form of regulation that precisely maintains the function of a system at a set point 1. Our study highlights the advantages of a paradoxical paracrine feedback loop in maintaining metabolic homeostasis. In addition, we find that the circuit facilitates coordinate secretion of both hormones in response to protein meals. This feature is related to the temporal delay in the rise of insulin concentrations in peripheral tissues, compared to the immediate hormone action on the liver. We find that the observed circuit dampens overshoots of blood glucose levels after reversion of glucose drops. We systematically simulate the dynamics of all possible islet inter-cellular connectivity patterns and analyze different performance criteria. Here we ask what are the design principles of this negative feedback loop. ![]() These two cell types are adjacently located in the islets of Langerhans and affect each others’ secretions in a paradoxical manner: while insulin inhibits glucagon secretion from alpha cells, glucagon seems to stimulate insulin secretion from beta cells. Mammalian glucose homeostasis is controlled by the antagonistic hormones insulin and glucagon, secreted by pancreatic beta and alpha cells respectively.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |