NOVARTIS EXHIBIT 2003
`Roxane v. Novartis, IPR 2016-01461
`Page 1 of 4
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`Anatomical plates provided by Branislav Vidic, Professor. Department of Anatomy
`and Cell Biology, Georgetown University, and by R.T. Hutchings from Color Atlas
`of Human Anatomy, edition 2, by R.M.H. McMinn and R.T. Hutchings, Mosby, 1988.
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`THIRD EDITION
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`NOVARTIS EXHIBIT 2003
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`Endocrine Glands
`
`d Cortisol inhibit CRH secretion from the hypo-
`_" lamus and thus constitute a negative-feedback in-
`a use on CRH secretion. In addition, high concen-
`teions of cortisol in the blood inhibit ACTH secre-
`" H from the anterior pituitary, and low concentra-
`'" 5 stimulate it. This negative-feedback loop is
`‘nortant
`in maintaining ‘blood cortisol
`levels
`ithin a narrow range of concentrations. In response
`stress or hypoglycemia, blood levels of cortisol in-
`6353 rapidly because these stimuli trigger a large
`Crease in CRH release from the hypothalamus.
`ble 18-9 outlines several abnormalities associated
`ith hypersecretion and hyposecretion of adrenal
`l‘I1'1011eS'
`
`Their effects in males are negligible in comparison
`to testosterone secreted by the testes. Chapter 28 pre-
`sents additional information about androgens.
`
`PANCREAS
`
`The pancreas (pan’kre-us) lies behind the peri-
`toneum between the greater curvature of the stom-
`ach and the duodenum. It is an elongated structure
`approximately 15 centimeters long, weighing ap-
`proximately 85 to 100 g. The head of the pancreas
`lies near the duodenum, and its body and tail extend
`toward the spleen.
`
`PREDICT
`
`Histology
`
`is some-
`ortisone, a drug similar to cortisol,
`times given to people who have severe allergies.
`Taking this substance chronically can damage
`the adrenal cortex. Explain how this damage can
`_DCCUf.
`
`drenal Androgen:
`including androstene-
`Some adrenal steroids,
`i one (an-dro-st”én’di-on), are weak androgens. They
`.u e secreted by the zona reticularis and converted by
`eripheral
`tissues to the more potent androgen,
`stosterone. Adrenal androgens - stimulate pubic
`nd axillary hair growth and sexual drive in females.
`
`The pancreas is both an exocrine gland and an
`endocrine gland. The exocrine portion consists of
`acini (as’i-ne), which produce pancreatic juice, and
`a duct system, which carries pancreatic juice to the
`small intestine (see Chapter 24]. The endocrine part,
`consisting of pancreatic islets [islets of Langerhans),
`(Figure 18-15) produces hormones that enter the cir-
`culatory system.
`Between 500,000 and 1,000,000 pancreatic islets
`are dispersed among the ducts and acini of the pan-
`creas. Each islet is composed of alpha cells (20%),
`which secrete glucagon, beta cells (75%), which se-
`crete insulin, and other cell types (5%). The remain-
`ing cells are either immature cells of questionable
`function or delta cells, which secrete somatostatin.
`Nerves from both divisions of the autonomic ner-
`vous system innervate the pancreatic islets, and
`
`FIGURE 18-15 HISTOLOGY OF THE PANCREATIC ISLETS Pancreatic islet cells consist of
`clusters of islet cells among the acini of the exocrine portion of the pancreas.
`
`Exocrine
`portions of
`pancreas
`
`Pancreatic
`islet
`
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`NOVARTIS EXHIBIT 2003
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`Integration and Control Systems
`
`TABLE 18-10 PANCREATIC HORMONES
`Cells In
`
`Response
`Target Tissue
`Structure
`Hormone
`Islets
`’
`Beta
`Insulin
`Protein
`
`Especially liver, skeletal muscle,
`
`fat tissue
`
`Alpha
`
`Glucagon
`
`Polypeptide
`
`Liver primarily
`
`Delta
`
`Somatostatin
`
`Peptide
`
`Alpha and beta cells (some somato-
`statin is produced in the hypo-
`thalamus)
`
`Increased uptake and use of glucose
`
`and amino acids
`Increased breakdown of glycogen;
`
`1
`
`release of glucose into the Circulatory
`system
`Inhibition of insulin and glucagon
`secretion
`
`TABLE 18-11 EFFECT OF INSULIN AND GLUCAGON ON TARGET TISSUES
`Response to Glucagon
`Little effect
`
`Target Tissue
`
`Skeletal muscle, cardiac muscle,
`cartilage, bone, fibroblasts,
`leukocytes, and mammary glands
`Liver
`
`Response to Insulin
`
`Increased glucose uptake and glyco-
`gen synthesis; increased uptake of
`certain amino acids
`
`Increased glycogen synthesis; in-
`creased use of glucose for
`energy (glycolysis)
`
`Causes rapid increase in the break-
`down of glycogen to glucose
`(glycogenolysis) and release of
`glucose into the blood
`Increased formation of glucose
`
`(gluconeogenesis) from amino acids
`and, to some degree, from fats
`Increased metabolism of fatty
`
`acids, resulting in increased ketones
`in the blood
`
`High concentrations cause break-
`down of fats (lipolysis); probably
`unimportant under most condi-
`tions
`No effect
`
`Adipose cells
`
`Nervous system
`
`Increased glucose uptake, glycogen
`synthesis, fat synthesis, and fatty
`acid uptake; increased glycolysis
`
`Little effect except to increase glu-
`cose uptake in the satiety center
`
`each islet is surrounded by a well—deVeloped capil-
`lary network.
`
`Effect of Insulin and Glucagon on Their
`
`Target Tissues
`The pancreatic hormones play an important role
`in regulating the concentration of critical nutrients
`in the Circulatory system, especially glucose or
`blood sugar and amino acids [Table 18-10]. The ma-
`jor target tissues of insulin are the liver, adipose tis-
`sue-, muscles, and the satiety center within the hy-
`pothalamus of the brain. The satiety (sa’-ti—é-te) cen-
`ter is a collection of neurons in the hypothalamus
`that controls appetite, but insulin does not directly
`
`affect most areas of the nervous system. The speC1f_1°
`effects of insulin on these target tissues are listed 1“
`Table 18-11.
`Insulin molecules bind to a membrane-bO1l_I1d re"
`ceptor on its target cells. Before the cells exhibit 8 T9‘
`sponse to insulin, specific proteins in the rnembrane
`become phosphorylated. Part of the cell’s 1‘€SP0nSe_
`to glucose is to increase the number of active traI15
`port proteins in the membrane of cells fol‘
`and amino acids. Subsequently, the ins
`ceptor molecules are taken through enclocym
`In.
`_
`the cell, and the insulin is released from the
`receptor and broken down. In general,
`illsuhnfl d-
`creases the ability of its target tissue to take UP 16%
`use glucose and amino acids. Glucose 11101
`that are not needed immediately as an energy 5
`
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