Insulin and Its Effects

To the average person, insulin is best known as the hormone that is deficient in people with diabetes, and it certainly was this relationship that spurred on the study of this fascinating hormone. We are just now realizing that insulin is involved in many cellular processes and in many different ways from what was previously thought. 

Insulin is a peptide hormone secreted from the pancreas. In its active form, it is a 51-amino-acid peptide with two different chains, the A chain and the B chain, held together by disulhde bonds. As described in Chapter 13, insulin was one of the hrst proteins to be cloned and expressed for human need. Insulin is created 

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White, M. F. Insulin Signaling in Health and Disease. Sdmce 302, 1710-1711 (2003). [A review of insulin and its effects on health.]... 

Insulin aspart is a rapid-acting synthetic insulin in which proline is replaced by aspartate at position 28 in the B chain. Insulin aspart has been reviewed (1). Its adverse effects do not differ from those of soluble human insulin and it has a similar effect on the blood glucose concentration (2). 

The potencies and the durations of action of oral hypoglycemic drugs vary (see Table 1). Oral drugs may make the cell more sensitive to insulin, and it is difficult to predict how long the hypoglycemic effect will last. The blood concentration does not always determine the... 

Nicorandil suppresses the release of insulin from isolated animal pancreatic cells (839). However, this effect is four times weaker than that of diazoxide, and its effect in man is not known. 

Sharma S, Chopra K, Kulkami SK. 2007. Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain Participation of nitric oxide and TNF-alpha. Phytother Res 21 278-283. 

Li, Y., Z. Shao, and A.K. Mitra. 1992. Dissociation of insulin oligomers by bile salt micelles and its effect on alpha-chymotrypsin-mediated proteolytic degradation. Pharm Res 7 864. 

Insulin is an antilipolytic hormone, and its effect on adipose tissue is to increase the transport of glucose into the fat cell, to stimulate lipogenesis and inhibit lipolysis. Thus, pyruvate dehydrogenase and acetyl-CoA carboxylase are activated, and the hormone-sensitive lipase is inactivated. In the normal, well-fed state insulin stimulates the deposition of fat. 

Sharma, P.M., Egawa, K., Huang, Y., Martin, J.L., Huvar, I., Boss, G.R., and Olefsky, J.M., 1998, Inhibition of phosphatidylinositol 3-kinase activity by adenovirus-mediated gene transfer and its effect on insulin action. J. Biol. Chem. 273 18528-18537. 

How does insulin exert its effects on insulin-sensitive tissues Insulin binds to receptors in the membranes of the skeletal muscle and adipose tissue. The irvsulin receptor has two a ubunits (each 135 kDa) and two p-subunits (each 95 kDa). Insulin binds to the a-subunit, which is extracellular, and provokes the p-subunit, which contacts the cytoplasm, to catalyse its own phosphorylation. Phosphorylation occurs on residues of tyrosine. This sequence is summarized by the following flowchart ... 

Insulin is used for the treatment of Type-I and for Type-II diabetes mellitus, when other therapeutic measures, i.e. appropriate diet and oral antidiabetics, are not sufficient to produce normoglycaemia. The physiological actions of insulin including recent advances in our knowledge on signal transduction have been discussed above (chapter 4). Since treatment of diabetes with insulin attempts only to supplement inadequate insulin secretion, this chapter will concentrate on pharmacokinetics, unwanted effects and clinical applications of insulin and its pharmaceutical preparations. 

Phosgene has been used as a condensing agent in peptide synthesis [2183], and its effect on the poiypeptide hormone, insulin, has been examined [1422,1423]. It is assumed that the COClj reacts preferentially with the amino groups of the insulin, and that inter- or intra-molecular linkages are created [1423] ... 

Insulin exerts its effects by altering the state of phosphorylation of certain intracellular enzymes by a mechanism that does not involve cAMP but that requires specific binding to surface receptors with tyrosine kinase activity. Insulin exerts acute (minutes), delayed-onset (hours), and longterm (days) effects entirely by way of a single receptor. 

Medication can be delivered via the eye in the form of eyedrops or in an ocular device. Sodium or zinc insulin was incorporated into a Gelfoam sponge-based device. An in vitro dissolution test indicated that the release of insulin from the device was proportional to the flow rate of the dissolution medium. An in vivo dissolution experiment provided support for the hypothesis that there was a direct relationship between the prolonged pharmacological response to insulin and its release from the device. The ocular device with or without the aid of an enhancer was placed in the eye of rabbits as an ocular insert and produced a uniform blood glucose-lowering effect of 60% over 8h. The blood glucose... 

Insulin belongs to a group of related hormones, all of which have profound effects on cellular metabolism. The exact function of each hormone varies from species to species, but in broad terms insulin and its cousins control the triangle of nutrition, reproduction and longevity. Insulin induces a shift in metabolism towards growth. When insulin is... 

Lew, A., Rutter, W. J., Kennedy, G. C. (2000). Unusual DNA structure of the diabetes susceptibility locus IDDM2 and its effect on transcription by the insulin promoter factor Pur-l/MAZ. Proc Natl Acad Sci U SA 91, 12508-12512. 

McMurthy, J.P, Rosebrough, R.W. Steele, N.C. (1987). Insulin metabolism and its effect on blood electrolytes and glucose in the turkey hea Comp. Biochem Physiol, 86A, 309-13. 

Saperstein R, Vicario PP, Strout HV, Brady E, Slater EE, Greenlee WJ, Ondeyka DL, Patchett AA, Hangauer DG (1989) Design of a selective insulin receptor tyrosine kinase inhibitor and its effect on glucose uptake and metabolism in intact cells. Biochemistry 28 5694-5701... 

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