A Second Messenger for Insulin

In animals, adrenomedullin dilates resistance vessels in the kidney, brain, lung, hind limbs, and mesentery, resulting in a marked, long-lasting hypotension. The hypotension in turn causes reflex increases in heart rate and cardiac output. Adrenomedullin also acts on the kidneys to increase sodium excretion, and exerts several endocrine effects including inhibition of aldosterone and insulin secretion. Finally it acts on the central nervous system to increase sympathetic outflow. These diverse actions of adrenomedullin are mediated both by CGRP receptors and unique adrenomedullin receptors, the properties of which are incompletely defined. The major second messenger for both receptors is cAMP. 

Synthesis of inositol phosphoglycans (IPGs) (71), analogues to second messengers of insulin, has been described. These derivatives contain the glucosamine (a 1-6) myo-inositol 1,2 cyclic phosphate motif and the thiol-terminated spacers for efficient coupling to maleimide functionalized solid phases or proteins. ... 

It is commonly agreed that cytosolic Ca2+ serves as a second messenger in stimulus-secretion coupling of insulin release (for a review see Heilman et al., 1992). 

The search for the second messenger for mediation of insulin action has up to now been as unsuccessful as the quest for high-energy intermediates of oxidative phosphorylation. A not unreasonable possibility, therefore, is that the second messenger does not exist as a separate chemical entity and that insulin action is mediated by electronic processes involving macromolecular semiconduction. Support for this view comes from the finding that the most rapid observed action of insulin is a hyperpolarization of the muscle cell plasma... 

Some water-soluble hormones bind to receptors with intrinsic protein kinase activity (often tyrosine kinases). In this case, no second messenger is required for protein kinase activation. The insulin receptor is an example of a tyrosine kinase receptor. 

Glucagon and insulin are only two of the many hormones that regulate vertebrate metabolism, and cAMP is only one of several so-called second messengers that transduce the hormone signal to the inside of the cell. In the remainder of this chapter we take a comprehensive look at the hormone systems that provide the main mechanisms for regulating energy metabolism and other metabolic activities as well. 

---