Cell Signaling

Lodish pgs. 534, 600, 618-619

 A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule.

 The response of a particular cell to a signal depends on the type of proteins it contains.

Seven major classes of membrane receptors

 Insulin is a key player in both carbohydrate and lipid metabolism, and has significant influences on protein and mineral metabolism. Defects in insulin signaling have widespread and devastating effects on many organs and tissues.
The amino acid sequence is highly conserved among vertebrates,
and many diabetic patients are treated with insulin extracted from pig pancreas.

 Insulin regulates blood glucose levels by increasing import of glucose by fat and muscle cells. Glucose is liberated from dietary carbohydrate such as starch or sucrose
by hydrolysis within the small intestine, and is then absorbed into the blood.

When blood glucose rises above its normal level, pancreatic bcells release insulin into the blood.

 The insulin receptor is a dimeric tyrosine kinase embedded in the plasma membrane. Two alpha subunits-extracellular, have insulin binding
domains. Two beta subunits linked by disulfide bonds-within and on cytosolic side of membrane.

 Binding of insulin to the alpha subunits causes the beta subunits to phosphorylate themselves (autophosphorylation), thus activating the catalytic activity of the receptor.

 Several intracellular proteins have been identified as phosphorylation substrates for the insulin receptor, the beststudied of which is insulin receptor substrate 1 or IRS-1. When IRS-1 is activated by phosphorylation, is serves as a type of
docking center for recruitment and activation of other enzymes.

 Activation of the insulin receptor will lead to the activation of the phosphatidylinositol-3 kinase (PI-3K) pathway. This pathway will activate protein kinase B (PKB).
PKB will inactivate glycogen synthetase 3 (GSK3) which normally inhibits glycogen synthase. When glycogen synthase is active, glucose monomers are synthesized into long chains of glycogen (liver and muscle).

 Protein kinase B causes movement of the GLUT4 glucose transporter from intracellular membranes to the cell surface. The influx of glucose will lower blood glucose levels.
When blood glucose levels return to normal, the GLUT4 transporters will be taken back into the cell by endocytosis.

PKB

 When glucose levels in the blood rise

Your cells may be starved for energy. Over time, high blood glucose levels can hurt your eyes, kidneys, nerves, and/or heart.

Diabetes mellitus is a metabolic disease that is characterized by abnormally high levels of glucose in the blood.
Type I or insulin-dependent diabetes is the result of a deficiency of insulin.
It

is due to destruction pancreatic b-cells, most likely the result of autoimmunity to one or more components of those cells. Usually begins in childhood. Many of the acute effects of this disease can be controlled by insulin replacement therapy.

Diabetes mellitus is a metabolic disease that is characterized by abnormally high levels of glucose in the blood.
Type

II or non-insulin-dependent diabetes begins as a syndrome of insulin resistance.

Target

tissues fail to respond appropriately to insulin. Typically, the onset of this disease is in adulthood. Despite monumental research efforts, the nature of the defect has been difficult to ascertain - in some patients, the insulin receptor is abnormal, in others, one or more aspects of insulin signaling is defective, and in others, no defect has been identified.

The disease is controlled through dietary therapy and hypoglycemic agents.