Mqe

hGH Dex Sum hGH+ Dex

FIGURE 15 Synergistic effects of human growth hormone (hGH) and the synthetic glucocorticoid dexamethasone (Dex) on lipolysis as measured by the increase in glycerol release from rat adipocytes. Both hGH and Dex were effective when added individually, but when added together their effect was greater than the sum of their individual effects. (From Gorin et al., Endocrinology 1990;126:2973.)

Mix Picture Push And Pull Actions

FIGURE 16 Push-pull mechanism. Epinephrine inhibits insulin secretion while promoting glucagon secretion. This combination of effects on the liver stimulates glucose production while simultaneously relieving an inhibitory influence.

Phosphorylase kinase

Phosphorylase kinase

Phosphorylase

Phosphorylase

(active) Phosphorylase 4

(active) Phosphorylase 4

Glucose

FIGURE 16 Push-pull mechanism. Epinephrine inhibits insulin secretion while promoting glucagon secretion. This combination of effects on the liver stimulates glucose production while simultaneously relieving an inhibitory influence.

Protein kinase A Glycogen Glucose -1 P

FIGURE 17 Push-pull mechanism to activate glycogen phosphor-ylase while simultaneously inhibiting glycogen synthase.

Glycogen Synthase (active)

Glycogen Synthase (active)

Glycogen Synthase PO4 (inactive)

FIGURE 17 Push-pull mechanism to activate glycogen phosphor-ylase while simultaneously inhibiting glycogen synthase.

for the adrenal cortical hormones, but appear to occur for other hormones as well. Permissive actions are not limited to responses to hormones, but pertain to any cellular response to any signal and presumably reflect some ongoing action of a hormone to maintain some basal cellular functions.

Push-Pull Mechanisms

Many critical processes are under dual control by agents that act antagonistically either to stimulate or to inhibit. Such dual control allows for more precise regulation through negative feedback. The example cited earlier was hepatic production of glucose, which is increased by glucagon and inhibited by insulin. In emergency situations or during exercise, epinephrine and norepinephrine released from the adrenal medulla and norepinephrine released from sympathetic nerve endings override both negative feedback systems by inhibiting insulin secretion and stimulating glucagon secretion (Fig. 16). The effect of adding a stimulatory influence and simultaneously removing an inhibitory influence is a rapid and large response, more rapid and larger than could be achieved by simply affecting either hormone alone, or than could be accomplished by the direct glycogenolytic effect of epinephrine or norepinephrine.

Another type of push-pull mechanism can be seen at the molecular level. Net synthesis of glycogen from glucose depends on the activity of two enzymes: glycogen synthase, which catalyzes the formation of glycogen from glucose, and glycogen phosphorylase, which catalyzes glycogen breakdown (Fig. 17). The net reaction rate is determined by the balance of the activity of the two enzymes. The activity of both enzymes is subject to regulation by phosphorylation, but in opposite directions: Addition of a phosphate group activates phosphorylase, but inactivates synthase. In this case, a single agent, cAMP, which activates protein kinase A, increases the activity of phosphorylase and simultaneously inhibits synthase.

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook


Post a comment