Insulin caffeine, effects

Mecftanism of Action AGI Hj-blocker and gastric acid secretion inhibitor that inhibits histamine action at histamine 2 receptors of parietal cells Therapeutic Effect Inhibits gastric acid secretion when fasting, at night, or when stimulated by food, caffeine, or insulin. 

Frankly toxic effects, such as persistent insomnia and anxiety, only become evident when people drink more than eight or nine cups of coffee or tea a day. Convulsions and delirium can follow enormous doses, and a near-fatal dose can induce a state similar to that of a diabetic lacking insulin. Blood sugar surges, and ketones appear in the urine. The lowest recorded fatal dose of caffeine was 3200 mg, which was given by accident directly into the bloodstream. It takes the equivalent of 40 cups of coffee consumed by mouth in a short interval for caffeine to kill a person. 

Raising intracellular levels of cyclic AMP stimulates lipolysis in fat pads and isolated cells (4) probably by activating the triglyceride lipase. The nucleotide also stimulates the conversion of phosphorylase b to phosphorylase in muscle and the conversion of the I form of glycogen synthetase to the D form (5, 6). It thus seemed possible that the inhibitory action of insulin on these processes might be mediated by a fall in tissue levels of cyclic AMP. Accordingly we have examined the effect of insulin on cyclic AMP levels in epididymal fat pads incubated with epinephrine and caffeine in the absence of glucose. 

In these experiments there was a poor correlation between the effects of insulin on cyclic AMP levels and lipolysis. When insulin had its most pronounced anti-lipolytic effects (i. e., in the presence of epinephrine alone) it did not appear to lower cyclic AMP, and when insulin lowered cyclic AMP (in tissue incubated with epinephrine and caffeine) it did not inhibit lipolysis. A small rise in the cyclic AMP level in adipose tissue (from about 1. 5 x 10 7 mmoles/g to 3. 5 x 10"7 mmoles/ g) is enough to stimulate lipolysis maximally and cyclic AMP... 

Galactose is metabolized slowly by adipose tissue and it thus became important to determine whether the effects of insulin, epinephrine and caffeine on the accumulation of galactose-Cl" were due to an effect on the transport of galactose into the cell or to effect on its subsequent metabolism. If, for example, insulin markedly stimulated the conversion of galactose-other radioactive products without affecting the... 

When isolated fat cells were incubated with glucose-U-CH insiolin produced the expected increase in incorporation of label into COz and lipid. Epinephrine stimulated incorporation of label in the absence of insulin but had little effect in the presence of insulin. Theophylline (or caffeine) inhibited incorporation of label into CQj and lipid both in the presence and absence of insulin. When epinephrine and theophylline were added to cells incubated with insulin, the inhibition of glucose incorporation was much greater than that seen with theophylline alone (Table 4). 

Cyclic AMP may also mediate the lipolytic effect of various hormones.99 Numerous lipolytic hormones (ACTH, glucagon, catecdiolamlnes, TSH, and others) Increase tissue levels of cyclic AMP by activation of adenyl cyclase.3-00 This effect Is potentiated by caffeine, an inhibitor of phosphodiesterase.3-80 Insulin, which lowers cyclic AMP levels also inhibits epinephrine induced lipolysis.301,102 Nicotinic acid, another lipolysls inhibitor, virtually obliterates the effects of epinephrine on cyclic AMP levels in isolated fat cells.303 xhe fact that exogenous cyclic A stimulates lipolysls in isolated fat cells301 adds further credence to the hypothesis that hormone induced lipolysls may be mediated by this nucleotide. 

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