Neurotransmitters, insulin secretion

In certain cells, however, an additional secretory pathway exists, the regulated secretory pathway. This pathway is found mainly in cells that are specialized for secreting products rapidly on demand in response to a particular stimulus (Fig. 1). For example, the hormone insulin and digestive enzymes are secreted by the pancreas, while neurotransmitters are secreted by nerve... 

Voltage-activated Ca " channels are activated by membrane depolarization and represent a large family of related channels with a wide tissue distribution. They are found ubiquitously in neurons, muscles, and endocrine cells as well as in many epithelial and endothelial cells. In addition to neurotransmitter release, they mediate a variety of essential functions in the body including muscle contraction, insulin secretion, gene expression, modulation of signal transduction events and in excess can cause cell death. 

Initiators of insulin secretion switch on the secretory machinery. Thereafter modulators derived from nutrient metabolism, hormones/peptides and neurotransmitters determine how fast or slow the machine will run. 

The most potent initiator of insulin secretion is glucose. Under physiological conditions its action is modulated by hormones, peptides and neurotransmitters as discussed later. 

MODULATION OF INSULIN SECRETION BY HORMONES. NEUROPEPTIDES AND NEUROTRANSMITTERS... 

Introduction. It is well-known that the hypothalamus participates in the regulation of carbohydrate metabolism via the autonomic nervous system. As far as the secretion of insulin is concerned, vagal stimulation causes release of insulin whereas adrenergic stimulation is inhibitory. Moreover, in addition to the classical neurotransmitters, neuropeptides present in the efferent autonomic nerves (GRP, VIP, peptide histidine-isoleucinamide (PHI), neuropeptide Y (NPY), CCK, galanin) are also of importance. The subject has previously been reviewed by Holst (1992). The existence of a cephalic phase of insulin secretion, i.e. reflex-stimulated secretion, has been well established in rats (Strubbe and Steffens, 1975), and there is also evidence for a cephalic-phase insulin response in humans (Bruce et al., 1987 Loud et al., 1988). 

Diagrammatic representation of insulin secretion from pancreatic fi cells. The sequence of events of insulin secretion coupled to glucose entry into fi cells consists of glucokinase action, ATP production, inhibition of the ATP-sensitive K+ channel, membrane depolarization, Ca + influx, and insulin release. Neurotransmitters acetylcholine and norepinephrine stimulate and inhibit insulin secretion via trimeric G-proteins Gq and Gj, respectively. Glucagon-like peptide (GLP) promotes insulin release via the G-protein G. Sulfonamides and diazoxide have direct effects on sulfonylurea receptors (SURs) the former promotes insulin release and the latter inhibits insulin release. +, Stimulation —, inhibition. Other abbreviations are given in the text. 

Membrane Stabilization. Calcium not only mediates secretion, but it also "stabilizes cell membranes, making it more difficult for calcium to enter cells. For example, if adrenal medulla is stimulated with 100 yg/ml of acetylcholine (the physiological neurotransmitter) at various calcium concentrations, catecholamine secretion increases as calcium increases up to at least 17.6 mM calcium (9). By contrast, pancreatic insulin secretion in response to glucose, peaks at 5.5 mM calcium and falls off at calcium concentrations on either side of the peak (10). So the relation between calcium concentration in the medium and the extent of secretion varies with the tissue and depends on the degree of membrane stabilization by calcium, a factor which influences the amount of calcium entering secretory cells. 

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

---