Hormones insulin

FIGURE 5.17 The hormone insulin consists of two polypeptide chains, A and B, held together by two disulfide cross-bridges (S—S). The A chain has 21 amino acid residues and an intrachain disulfide the B polypeptide contains 30 amino acids. The sequence shown is for bovine insulin. 

Loss of the cell s responsiveness to the hormone insulin caused by pathological alterations in the insulin receptor signal transduction pathway, and often leading... 

The predominant cell type in the pancreatic islets of Langerhans. The main secretory product of the (3 -cell is the peptide hormone insulin which has vital actions for the control of nutrient homeostasis and cellular differentiation. 

In addition to the direct effects of hyperglycemia in enhancing the uptake of glucose into the liver, the hormone insulin plays a central role in regulating blood glucose. It is produced by the B cells of the islets of Langerhans in the pancreas in response to hyperglycemia. The B islet cells are freely permeable to glu-... 

The amino group of the N-terminal amino acid residue of a peptide will react with the FDNB reagent to form the characteristic yellow DNP derivative, which may be released from the peptide by either acid or enzymic hydrolysis of the peptide bond and subsequently identified. This is of historic interest because Dr F. Sanger first used this reaction in his work on the determination of the primary structure of the polypeptide hormone insulin and the reagent is often referred to as Sanger s reagent. 

One could plunge into the steric problems posed by the mechanism of protein synthesis on the ribosome 25 26)> or consider the steric fit of the hormone insulin to its acceptor in the cell membrane 27>. Or one could delve into the beautiful intricacy of terpenoid, squalene and steroid metabolism, or get lost in double bond formation, or in the steric problems posed by the branched chain fatty acids and their derivatives 28-34). 

Theoretically, diabetes could be as readily caused by overproduction of the pituitary hormone as by the underproduction of insulin. Actually both activities probably vary greatly, and the diabetes results from an imbalance. Even when diabetes has its origin in an overactivity of the pituitary in producing the diabetogenic hormone, insulin may still be an effective remedy. Actually, of course, diabetes is sometimes insulin-resistant, which fact reveals that the disease does not always have the same origin. 

Specific hormones Insulin, glucagon, somatostatin, gastrin, pancreatic polypeptide, serotonin, vasoactive intestinal peptide, cholecystokinin... 

Muscle All the amino acids are required for protein synthesis so that the transporters are important particularly during growth. Consistent with this, the major anabolic hormone, insulin, increases the transport of some amino acids into the muscle, which contributes to the stimulation of protein synthesis by insulin. 

The hormone insulin decreases the rate of fatty acid oxidation via two mechanisms. 

Figure 7.14 Regulation of rate of fatty acid oxidation in tissues. Arrows indicate direction of change (i) Changes in the concentrations of various hormones control the activity of hormone-sensitive lipase in adipose tissue (see Figure 7.10). (ii) Changes in the blood level of fatty acid govern the uptake and oxidation of fatty acid, (iii) The activity of the enzyme CPT-I is controlled by changes in the intracellular level of malonyl-CoA, the formation of which is controlled by the hormones insulin and glucagon. Insulin increases malonyl-CoA concentration, glucagon decrease it. Three factors are important TAG-lipase, plasma fatty acid concentration and the intracellular malonyl-CoA concentration.

The effector systems result in changes in messenger systems that then cause the effects of the hormone. Not surprisingly, the effects of the hormone depend on which hormone is being considered. To illustrate this four hormones - insulin, cortisol, adrenaline and glucagon - are discussed. 

The peptide hormone insulin (see Box 13.1) is produced by the pancreas and plays a key role in the regulation of carbohydrate, fat, and protein metabolism, hi particular, it has a hypoglycaemic effect, lowering the levels of glucose in the blood. A malfunctioning pancreas may produce a deficiency in insulin synthesis or secretion, leading to the condition known as diabetes mellitus. This results in increased amounts of glucose in the blood and urine, diuresis, depletion of carbohydrate stores, and subsequent breakdown of fat and protein. Incomplete breakdown of fat leads to the accumulation of ketones in the blood, severe acidosis, coma, and death. 

In contrast to glucagon, the peptide hormone insulin (see p. 76) increases glycogen synthesis and inhibits glycogen breakdown. Via several intermediates, it inhibits protein kinase GSK-3 (bottom right for details, see p. 388) and thereby prevents inactivation of glycogen synthase. In addition, insulin reduces the cAMP level by activating cAMP phosphodiesterase (PDE). 

The receptor for the hormone insulin (see p. 76) belongs to the family of 1-helix receptors. 

The signal transduction pathways that mediate the effects of the metabolic hormone insulin are of particular medical interest (see A). The mediator nitrogen monoxide (NO) is also clinically important, as it regulates vascular caliber and thus the body s perfusion with blood (see B). 

C. Blood glucose is regulated by the hormones insulin, glucagon, and epinephrine. 

Diacylglycerol, on the other hand, is lipid soluble and remains in the lipid bilayer of the membrane. There it can activate protein kinase C (PKC), a very important and widely distributed enzyme which serves many systems through phosphorylation, including neurotransmitters (acetylcholine, a,- and P-adrenoceptors, serotonin), peptide hormones (insulin, epidermal growth hormone, somatomedin), and various cellular functions (glycogen metabolism, muscle activity, structural proteins, etc.), and also interacts with guanylate cyclase. In addition to diacylglycerol, another normal membrane lipid, phos-phatidylserine, is needed for activation of PKC. The DG-IP3 limbs of the pathway usually proceed simultaneously. 

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