Enzymes insulin effect

In addition to its effects on the activity of existing enzymes, insulin also regulates the expression of as many as 150 genes, including some related to fuel metabolism... 

The foregoing section indicates some reasons why peptide-based drugs are needed. If a peptide hormone is not produced in sufficient quantities or is defective in structure, then a replacement is required. Peptides, especially very small molecules, have a very short half life in the body. The reason for this is the ubiquitous occurrence of proteolytic enzymes that effect hydrolysis of peptides to the constituent amino acids. Although longer peptides, especially those with structural features such as disulphide bonds, survive longer in vivo, they are more likely to stimulate the body s immune system to produce antibodies and effect removal of the peptides. This is particularly likely to occur with molecules that differ structurally from the naturally occurring hormones. Thus, treatment of juvenile-onset diabetes mellitus with insulins from animal sources can occasionally stimulate the patient s immune system... 

This trace element is a cofactor along with the hormone insulin in regulating blood sugar. Chromium enhances insulin effectiveness by increasing cell sensitivity to insulin. No chromium-dependent enzymes have been discovered. 

Moreover DBcAMP did not inhibit the hydrolysis of cAMP by heart phosphodiesterase, indicating a failure to bind to the enzyme. Since DBcAMP is not degraded by the diesterase its biological activity should not be influenced by those materials which either inhibit (theophylline) or stimulate (insulin, nicotinic acid, imidazole) the enzyme. The effect of these compounds on llpolysls produced by DBcAMP has been studied with somewhat conflicting results. Theophylline was found to potentiate DBcAMP-Induced lipolysis24,79 and nicotinic acid inhibited DBcAMP-induced lipo-lysls27,79. Insulin and imidazole have been reported to have either no effect or to inhibit lipolysis induced by DBcAMP. These results are difficult to interpret at this time. 

Fatty acid synthetase is also subject to both adaptive changes in enzyme content as well as short-term metabolic control. The latter effects are ill-defined (Wakil et al., 1983) but diet, triiodothyronine, hydrocortisone and insulin effects have been noted on the amount of synthetase protein. Hydrocortisone and tri-iodothyronine have no effect alone but potentiate the insulin induction of synthetase (Wakil et al., 1983). The increases in synthetase activity on refeeding or insulin administration are due to an increase in transcription of mRNA which is elevated 70-fold (Morris et al., 1982). 

Also, phosphorylation of Akt results in activation of sterol regulatory-element binding protein 1 (SREBP1), a key transcription factor involved in regulation of lipogenic enzymes. In addition, some of the effects of insulin on cell proliferation and survival may be explained by an Akt-dependent inhibition of apoptosis through phosphorylation and inactivation of proa-poptotic proteins (e.g., BAD, Caspase 9). 

Diabetic patients have reduced antioxidant defences and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. EC has a pronounced insulin-like effect on erythrocyte membrane-bound acetylcholinesterase in type II diabetic patients (Rizvi and Zaid, 2001). Tea polyphenols were shown to possess anti-diabetic activity and to be effective both in the prevention and treatment of diabetes (Choi et al, 1998 Yang et al, 1999). The main mechanism by which tea polyphenols appear to lower serum glucose levels is via the inhibition of the activity of the starch digesting enzyme, amylase. Tea inhibits both salivary and intestinal amylase, so that starch is broken down more slowly and the rise in serum glucose is thus reduced. In addition, tea may affect the intestinal absorption of glucose. 

DPP-4 is a serine protease that inactivates GLP-1. GLP-1 stimulates insulin secretion and suppresses glucagon release. The inhibition of DPP-4 prolongs the half-life of GLP-1 and brings about beneficial effects on glucose levels and glucose tolerance in type 2 diabetics. Backes et al. [64] report on the parallel optimization of enzyme binding affinity and inhibition, selectivity, ADME properties, and PK (Scheme 19). 

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