Department of medical physiology 11 th week Semester: summer Study program: Dental medicine Lecture: RNDr. Soňa Grešová, PhD.
1. Pancreas Hormones 2. Pituitary Hormones and their control by the hypothalamus
Pancreas Hormones: Insulin Glucagon Amylin Somatostatin Pancreatic polypeptide
Anatomy of the Pancreas is composed of two major types of tissues: 1) the acini (digestive juices) 2) the islets of Langerhans (insulin and glucagon) three major types of cells, alpha, (25%, glucagon) beta, (60%, insulin, amylin) delta cells (10%, somatostatin PP cells (pancreatic polypeptide) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Cell-to-cell communication and direct control of secretion Insulin inhibits glucagon secretion, Amylin inhibits insulin secretion, Somatostatin inhibits the secretion of both insulin and glucagon
Insulin Insulin and its metabolic effects insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism Insulin is a hormone associated with energy abundance excess amounts of carbohydrates = insulin is secreted in great quantity insulin plays an important role in storing the excess energy (glycogen = liver, muscles) excess carbohydrates that cannot be stored as glycogen are converted under the stimulus of insulin into fats and stored in the adipose tissue insulin has a direct effect in conversion of amino acids into protein (inhibits the breakdown of the proteins that are already in the cells)
Insulin synthesis Insulin is synthesized in the beta cells with translation of the insulin RNA by ribosomes attached to the endoplasmic reticulum to form an insulin preprohormone is then cleaved in the endoplasmic reticulum to form a proinsulin this is further cleaved in the Golgi apparatus to form insulin and peptide fragments before being packaged in the secretory granules insulin is secreted into the blood in an unbound form (halflife -6 minutes, cleared from the circulation within 10 to 15 minutes) is degraded by the enzyme insulinase mainly in the liver, to a lesser extent in the kidneys and muscles, and slightly in most other tissues
Activation of target cell receptors by Insulin insulin binds and activates a membrane receptor protein binds with the alpha subunits on the outside of the cell the beta subunits protruding into the cell become autophosphorylated the receptor activates a local tyrosine kinase - phosphorylation of multiple other intracellular enzymes effects on carbohydrate, fat, and protein metabolism Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Effect of insulin on carbohydrate metabolism The insulin in turn causes rapid uptake, storage, and use of glucose by almost all tissues of the body, but especially by the muscles, adipose tissue, and liver Insulin promotes muscle glucose uptake and metabolism Storage of glycogen in muscle The glycogen can later be used for energy by the muscle Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Effect of insulin on carbohydrate metabolism Insulin promotes liver uptake, storage, and use of glucose Insulin inactivates liver phosphorylase Insulin increasing the activity of the enzyme glucokinase Insulin also increases the activities of the enzymes especially glycogen synthase The net effect of all these actions is to increase the amount of glycogen in the liver Glucose is released from the liver between meals The decreasing blood glucose causes the pancreas to decrease its insulin secretion then reverses all the effects for glycogen storage
Effect of insulin on carbohydrate metabolism Insulin promotes conversion of excess glucose into fatty acids and inhibits gluconeogenesis in the liver Insulin promotes conversion of excess glucose into fatty acids = packaged as VLDL - transported to the adipose tissue and deposited as FAT inhibits gluconeogenesis in the liver by decreasing the quantities and activities of the liver enzymes required for gluconeogenesis
Effect of insulin on carbohydrate metabolism Lack of effect of insulin on glucose uptake and usage by the brain the brain cells are permeable to glucose and can use glucose without the intermediation of insulin (retina, germinal epithelium of the gonads)
Effect of insulin on fat metabolism Insulin promotes fat synthesis and storage Insulin increases the transport of glucose into the liver cells (The glucose is first split to pyruvate in the glycolytic pathway, and the pyruvate subsequently is converted to acetyl coenzyme A (acetyl-coa), the substrate from which fatty acids are synthesized Most of the fatty acids are then synthesized within the liver itself and used to form triglycerides Role of insulin in storage of fat in the adipose cells Insulin inhibits the action of hormone-sensitive lipase Insulin promotes glucose transport through the cell membrane into the fat cells
Effect of insulin on fat metabolism Insulin deficiency increases use of fat for energy Insulin deficiency causes lipolysis of storage fat and release of free fatty acids Insulin deficiency increases plasma cholesterol and phospholipid concentrations Excess usage of fats during insulin lack causes ketosis and acidosis Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Effect of Insulin on protein metabolism and on growth Insulin promotes protein synthesis and storage Insulin stimulates transport of many of the amino acids into the cells (valine, leucine, isoleucine, tyrosine, phenylalanine) Insulin increases the translation of messenger RNA, insulin also increases the rate of transcription of selected DNA genetic sequences Insulin inhibits the catabolism of proteins In the liver, insulin depresses the rate of gluconeogenesis
Mechanisms of insulin secretion by the pancreatic beta cells glucose transporters (GLUT- 2) glucose is phosphorylated to glucose-6-phosphate by glucokinase Oxidation to form adenosine triphosphate (ATP) Inhibition the ATP-sensitive potassium channels opening voltage-gated calcium channels, fusion of the docked insulincontaining vesicles secretion of insulin into the extracellular fluid by exocytosis Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Control of insulin secretion Increased blood glucose stimulates insulin secretion Feedback relation between blood glucose concentration and insulin secretion rate Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Control of insulin secretion Other factors that stimulate insulin secretion Amino acids (arginine, lysine) Gastrointestinal hormones (gastrin, secretin, cholecystokinin, incretins) Other hormones and the autonomic nervous system glucagon, growth hormone, cortisol, and, to a lesser extent, progesterone and estrogen Parasympathetic increase insulin secretion during hypeglycemic conditions Symphatetic increase glucagon secretion and decrease insulin secretion during hypoglycemia Epinephrine is especially important in increasing plasma glucose concentration, far greater increases fatty acids during periods of stress
Control of insulin secretion Glucose concentrations are believed to be detected by specialized neurons of the hypothalamus and brain stem, as well as by glucose-sensing cells in peripheral locations such as the liver
Glucagon and its functions Glucagon, a hormone secreted by the alpha cells of the islets of Langerhans several functions that are diametrically opposed to those of insulin increases the blood glucose concentration glucagon is also called the hyperglycemic hormone
Glucagon and its functions Effects on glucose metabolism 1) breakdown of liver glycogen (glycogenolysis) 1. Glucagon activates adenylyl cyclase in the hepatic cell membrane, 2. the formation of cyclic adenosine monophosphate, 3. activates protein kinase regulator protein, 4. activates protein kinase, 5. activates phosphorylase b kinase, 6. converts phosphorylase b into phosphorylase a, 7. promotes the degradation of glycogen into glucose-1-phosphate, 8. which then is dephosphorylated; and the glucose is released from the liver cells 2) increased gluconeogenesis in the liver by activating multiple enzymes that are required for amino acid transport and gluconeogenesis in the liver, (converting pyruvate to phosphoenolpyruvate)
Glucagon and its functions Other effects of glucagon activates adipose cell lipase, making increased quantities of fatty acids available to the energy systems of the body Inhibits the storage of triglycerides in the liver Very high concentrations of glucagon 1) enhances the strength of the heart; 2) increases blood flow in some tissues, especially the kidneys; 3) enhances bile secretion; 4) inhibits gastric acid secretion
Regulation of glucagon secretion Increased blood glucose inhibits glucagon secretion Increased blood amino acids stimulate glucagon secretion (alanine, arginine) rapid conversion of AA to glucose Exercise stimulates glucagon secretion Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Regulation of glucagon secretion Somatostatin inhibits glucagon and insulin secretion The delta cells of the islets of Langerhans secrete the hormone somatostatin Somatostatin acts locally within the islets of Langerhans themselves to depress the secretion of both insulin and glucagon Somatostatin decreases the motility of the stomach, duodenum, and gallbladder Somatostatin decreases both secretion and absorption in the gastrointestinal tract
Diabetes Mellitus 1. Type I diabetes, also called insulin-dependent diabetes mellitus (IDDM), is caused by lack of insulin secretion 2. Type II diabetes, also called non insulindependent diabetes mellitus (NIDDM), is caused by decreased sensitivity of target tissues to the metabolic effect of insulin. This reduced sensitivity to insulin is often called insulin resistance.
Pituitary Hormones and their control by the hypothalamus
Pituitary gland (hypophysis) The anterior pituitary gland (adenohypophysis) Six important peptide hormones plus several less important ones Posterior pituitary gland (neurohypophysis) two important peptide hormones Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Pituitary gland (hypophysis) The hormones of the anterior pituitary play major roles in the control of metabolic functions throughout the body Growth hormone Adrenocorticotropin (corticotropin Thyroid-stimulating hormone (thyrotropin) Prolactin two separate gonadotropic hormones, follicle-stimulating hormone and luteinizing hormone, The two hormones secreted by the posterior pituitary play other roles Antidiuretic hormone (vasopressin Oxytocin Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Anterior pituitary gland five cell types are: 1. Somatotropes human growth hormone (hgh) 2. Corticotropes adrenocorticotropin (ACTH) 3. Thyrotropes thyroid-stimulating hormone (TSH) 4. Gonadotropes gonadotropic hormones, which include both luteinizing hormone (LH) and folliclestimulating hormone (FSH) 5. Lactotropes prolactin (PRL) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Posterior pituitary hormones The bodies of the cells are large neurons, called magnocellular neurons, located in the supraoptic and paraventricular nuclei of the hypothalamus The hormones are then transported in the axoplasm of the neurons to the posterior pituitary gland
Hypothalamus controls pituitary secretion Secretion from the posterior pituitary is controlled by nerve signals that originate in the hypothalamus and terminate in the posterior pituitary Secretion by the anterior pituitary is controlled by hormones called hypothalamic releasing and hypothalamic inhibitory hormones (or factors) blood vessels = hypothalamichypophysial portal vessels Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Hypothalamic-Hypophysial portal blood vessels of the anterior pituitary gland Hypothalamic releasing and inhibitory hormones are secreted into the median eminence and tuber cinereum, an extension of hypothalamic tissue into the pituatory stalk tissue fluid sinuses of the anterior pituitary Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Hypothalamic-Hypophysial portal blood vessels of the anterior pituitary gland Hypothalamic releasing hormons Preoptic nc. release: Gonadotropin-releasing hormone (GnRH), which causes release in anterior pituitary (basophilic cells) of the two gonadotropic hormones, luteinizing hormone and folliclestimulating hormone Male - spermatogenesis, production of testosteron Female oogenesis, ovulation, production estrogen and pregesteron Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Hypothalamic-Hypophysial portal blood vessels of the anterior pituitary gland Hypothalamic releasing and inhibitory hormon Ventromedial nc. release: Growth hormone releasing hormone (GHRH), which causes release of growth hormone, and growth hormone inhibitory hormone (GHIH), called somatostatin, to the anterior pituitary (acidophilic cells) which inhibits release of growth hormone Growth hormone acts directly from blood and in liver is made somatomedin Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Hypothalamic-Hypophysial portal blood vessels of the anterior pituitary gland Hypothalamic releasing hormons Paraventricular nc. release: Thyrotropin-releasing hormone (TRH), which causes release of thyroid-stimulating hormone (TSH) from anterior pituitary (basophilic cells) T3, T4 Corticotropin-releasing hormone (CRH), which causes release of adrenocorticotropin (ACTH) (basophilic cells) glucocorticoids (adrenal cortexzona fasciculata) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Hypothalamic-Hypophysial portal blood vessels of the anterior pituitary gland Hypothalamic inhibitory hormons Arcuate nc. release: Prolactin inhibitory hormone (PIH) dopamin, which causes inhibition of prolactin secretion (acidophilic cells) Increase production of milk Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Physiological functions of growth hormone Growth hormone (somatotropic hormone or somatotropin) promotes growth of many body tissues it promotes increased sizes of the cells and increased mitosis, with development of greater numbers of cells and specific differentiation of certain types of cells such as bone growth cells and early muscle cells Growth hormone enhances body protein, decreases fat stores, and conserves carbohydrates Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Physiological functions of growth hormone Growth hormone enhances almost all facets of amino acid uptake and protein synthesis by cells, while at the same time reducing the breakdown of proteins Metabolic effects: Growth hormone promotes protein deposition in tissues Enhancement of amino acid transport through the cell membranes increasing protein synthesis Enhancement of RNA translation to cause protein synthesis by the ribosomes even AA concentrations are not increased Increased nuclear transcription of DNA to form RNA if sufficient energy, amino acids, vitamins, and other requisites for growth are available Decreased catabolism of protein and amino acids Mobilizes large quantities of free fatty acids from the adipose tissue (energy)
Physiological functions Metabolic effects: of growth hormone Growth hormone enhances fat utilization for energy has a specific effect in causing the release of fatty acids from adipose tissue increasing the concentration of fatty acids in the body fluids Enhances the conversion of fatty acids to acetyl coenzyme A (acetyl-coa) its subsequent utilization for energy Excessive mobilization of fat from the adipose tissue frequently causes ketosis and a fatty liver
Physiological functions of growth hormone Metabolic effects: Growth hormone decreases carbohydrate utilization 1) decreased glucose uptake in tissues such as skeletal muscle and fat, 2) increased glucose production by the liver, 3) increased insulin secretion Necessity of insulin and carbohydrate for the growthpromoting action of growth hormone adequate insulin activity and adequate availability of carbohydrates are necessary for growth hormone to be effective
Physiological functions Metabolic effects: of growth hormone Growth hormone stimulates cartilage and bone growth 1) Increased deposition of protein by the chondrocytic and osteogenic cells that cause bone growth, 2) Increased rate of reproduction of these cells, 3) a specific effect of converting chondrocytes into osteogenic cells, thus causing deposition of new bone
Physiological functions of growth hormone Metabolic effects: Growth hormone exerts much of its effect through intermediate substances called somatomedins (also called insulin-like growth factors ) Growth hormon in liver releasing of somatomedins Short duration of action of growth hormone but prolonged action of somatomedin C (bounded with plasma proteins) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Regulation of growth hormone secretion Growth hormone is secreted in a pulsatile pattern, increasing and decreasing person s state of nutrition or stress - stimulate secretion 1) starvation, especially with severe protein deficiency; 2) hypoglycemia or low concentration of fatty acids in the blood; 3) exercise; 4) excitement; 5) trauma 6) ghrelin Growth hormone increases during the first 2 hours of deep sleep Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Regulation of growth hormone secretion Role of the hypothalamus in the control of growth hormone secretion growth hormone releasing hormone, growth hormone inhibitory hormone - somatostatin are transported to the anterior pituitary gland through the hypothalamichypophysial portal vessels Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Abnormalities of growth hormone secretion Panhypopituitarism This term means decreased secretion of all the anterior pituitary hormones (present from birth) Dwarfism result from generalized deficiency of anterior pituitary secretion (panhypopituitarism) during childhood Panhypopituitarism in the Adult The general effects: 1) hypothyroidism, 2) depressed production of glucocorticoids by the adrenal glands, 3) suppressed secretion of the gonadotropic hormones so that sexual functions are lost Gigantism the acidophilic, growth hormone producing cells of the anterior pituitary gland become excessively active, and sometimes even acidophilic tumors occur in the gland the condition occurs before adolescence, before the epiphyses of the long bones have become fused with the shafts, height increases so that the person becomes a giant up to 8 feet tall diabetes mellitus Acromegaly an acidophilic tumor occurs after adolescence that is, after the epiphyses of the long bones have fused with the shafts the person cannot grow taller, but the bones can become thicker and the soft tissues can continue to grow membranous bones, kyphosis Possible role of decreased Growth hormone secretion in causing changes associated with aging Therapy in older people : 1) increased protein deposition in the body, especially in the muscles; 2) decreased fat deposits; 3) a feeling of increased energy
Posterior pituitary gland (neurohypophysis) terminal nerve endings from nerve tracts that originate in the supraoptic and paraventricular nuclei of the hypothalamus endings lie on the surfaces of capillaries, where they secrete two posterior pituitary hormones: 1) antidiuretic hormone (ADH), also called vasopressin, (supraoptic nuclei) 2) oxytocin (primarily in the paraventricular nuclei) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Physiological functions of ADH ADH acts on the collecting ducts to increase their permeability (aquaporins) Regulation of ADH production Osmotic regulation Osmoreceptors : the extracellular fluid becomes too concentrated, fluid is pulled by osmosis out of the osmoreceptor cell, decreasing its size and initiating appropriate nerve signals in the hypothalamus to cause additional ADH secretion
Physiological functions of ADH Regulation of ADH production Vasoconstrictor and pressor effects of ADH, and increased ADH secretion caused by low blood volume The stimuli for causing intense ADH secretion is decreased blood volume The atria have stretch receptors that are excited by overfilling (inhibition of ADH secretion) Decreased stretch of the baroreceptors of the carotid aortic, and pulmonary regions (stimulation ADH secretion)
Oxytocin hormone Oxytocin causes contraction of the pregnant uterus stimulates contraction of the pregnant uterus, especially toward the end of gestation Oxytocin aids in milk ejection by the breasts In lactation, oxytocin causes milk to be expressed from the alveoli into the ducts of the breast Stimulus suckling stimulus on the nipple of the breast - release of oxytocin by the posterior pituitary gland - contraction of myoepithelial cells (milk letdown or milk ejection)