Copyright 2009, John Wiley & Sons, Inc. Pancreas Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. Pancreatic Islets Both exocrine and endocrine gland Roughly 99% of cells produce digestive enzymes Pancreatic islets or islets of Langerhans Alpha or A cells secrete glucagon – raises blood sugar Beta or B cells secrete insulin – lowers blood sugar Delta or D cells secrete somatostatin – inhibits both insulin and glucagon F cells secrete pancreatic polypeptide – inhibits somatostatin, gallbladder contraction, and secretion of pancreatic digestive enzymes Copyright 2009, John Wiley & Sons, Inc.

Cell Types in the Pancreatic Islets Alpha cells (20%) produce glucagon Beta cells (70%) produce insulin Delta cells (5%) produce somatostatin F cells produce pancreatic polypeptide

Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis Blood glucose level falls Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 7 Insulin acts on various body cells to: • accelerate facilitated diffusion of glucose into cells • speed conversion of glucose into glycogen (glycogenesis) • increase uptake of amino acids and increase protein synthesis • speed synthesis of fatty acids (lipogenesis) • slow glycogenolysis • slow gluconeogenesis If blood glucose continues to fall, hypoglycemia inhibits release of insulin Blood glucose level falls Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete INSULIN GLUCAGON 1 5 2 3 4 6 7 8 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete High blood glucose (hyperglycemia) stimulates beta cells to secrete GLUCAGON 1 5 2 3 4 INSULIN Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal If blood glucose continues to rise, hyperglycemia inhibits release of glucagon Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 3 4 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 Glucagon acts on hepatocytes (liver cells) to: • convert glycogen into glucose (glycogenolysis) • form glucose from lactic acid and certain amino acids (gluconeogenesis) Glucose released by hepatocytes raises blood glucose level to normal Low blood glucose (hypoglycemia) stimulates alpha cells to secrete GLUCAGON 1 2 3 Low blood glucose (hypoglycemia) stimulates alpha cells to secrete 1 GLUCAGON

Copyright 2009, John Wiley & Sons, Inc. Pineal Gland Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. Pineal Gland Attached to roof of 3rd ventricle of brain at midline Masses of neuroglia and pinealocytes Melatonin – amine hormone derived from serotonin Appears to contribute to setting biological clock More melatonin liberated during darkness than light Copyright 2009, John Wiley & Sons, Inc.

SCN and sleep Wild type animal with period of ~24h Tau mutant Basics of Sleep Guide: Chronobiology SCN and sleep 4/24/2017 4/24/2017 Wild type animal with period of ~24h Tau mutant with period of ~20h A SCN lesioning B Transplanting SCN of donor with ~20-h period C SCN lesioning abolishes circadian rhythm Wild type animal acquires period of donor (~20h) Modified from Ralph and Lehman, Trends Neuro 1991 Scheer-Shea Set #8 8 8

Melatonin: Produced by pineal gland, released at night-inhibited during the day (circadian regulation); initiates and maintain sleep; treat symptoms of jet lag and insomnia

Hypothalamus and Pituitary Gland

Copyright 2009, John Wiley & Sons, Inc. Anterior pituitary Release of hormones stimulated by releasing and inhibiting hormones from the hypothalamus Also regulated by negative feedback Hypothalamic hormones made by neurosecretory cells transported by hypophyseal portal system Anterior pituitary hormones that act on other endocrine systems called tropic hormones Copyright 2009, John Wiley & Sons, Inc.

Hormones of the Anterior Pituitary Human growth hormone (hGH) or somatotropin Stimulates secretion of insulin-like growth factors (IGFs) that promote growth, protein synthesis Thyroid-stimulating hormone (TSH) or thyrotropin Stimulates synthesis and secretion of thyroid hormones by thyroid Follicle-stimulating hormone (FSH) Ovaries initiates development of oocytes, testes stimulates testosterone production Luteinizing hormone (LH) Ovaries stimulates ovulation, testes stimulates testosterone production Copyright 2009, John Wiley & Sons, Inc.

Hormones of the Anterior Pituitary Prolactin (PRL) Promotes milk secretion by mammary glands Adrenocorticotropic hormone (ACTH) or corticotropin Stimulates glucocorticoid secretion by adrenal cortex Melanocyte-stimulating Hormone (MSH) Copyright 2009, John Wiley & Sons, Inc.

Function of Anterior Pituitary Hormones Copyright 2009, John Wiley & Sons, Inc.

1) Human Growth Hormone Increases synthesis of insulin-like growth factors “(IGFs) or somatomedins” at target cells target cells are liver, skeletal muscle, cartilage and bone. IGF will work locally or enter bloodstream and they will lead to: increases cell growth & cell division Increases cell uptake of amino acids & synthesis of proteins stimulate lipolysis in adipose so fatty acids used for ATP retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain Increases plasma free fatty acids (FFA) - source of energy for muscle tissue Increases hepatic glucose output Decreases insulin sensitivity in muscle Is protein anabolic hormone

Regulation of hGH Low blood sugar stimulates release of GNRH from hypothalamus anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells High blood sugar stimulates release of GHIH from hypothalamus less hGH from anterior pituitary, glycogen does not breakdown into glucose

Diabetogenic Effect of Human Growth Hormone Excess of growth hormone raises blood glucose concentration pancreas releases insulin continually beta-cell burnout Diabetogenic effect causes diabetes mellitis

2) Thyroid Stimulating Hormone (TSH) Hypothalamus regulates the production of Thyroid Stimulating Hormone (TSH) TSH stimulates the synthesis & secretion of T3 and T4 at thyroid gland Metabolic rate stimulated

3) Follicle Stimulating Hormone (FSH) FSH functions initiates the formation of follicles within the ovary stimulates follicle cells to secrete estrogen stimulates sperm production in testes

4) Luteinizing Hormone (LH) In females, LH stimulates secretion of estrogen(with FSH) ovulation of secondary oocyte from ovary formation of corpus luteum secretion of progesterone In males, stimulates interstitial cells to secrete testosterone

5) Prolactin (PRL) Under right conditions, prolactin causes milk production Suckling reduces cause prolactin levels rise along with milk production Nursing ceases & milk production slows

6) Adrenocorticotrophic Hormone ACTH stimulates cells of the adrenal cortex that produce glucocorticoids

7) Melanocyte-Stimulating Hormone Releasing hormone from hypothalamus increases its release From the anterior pituitary Function not certain in humans (increase skin pigmentation in frogs )

Regulation of Ant. Pitutary Hormone Secretion negative feedback Hypothalamus Copyright 2009, John Wiley & Sons, Inc.

Hypothalamus Hypothalamus is a section of brain above where pituitary gland is suspended from by infundibulum or stalk

Functions of hypothalamus Endocrine function Caloric balance Osmolarity balance Thermal regulation Autonomic balance Sleep Affective behavior Memory Somatic movements

Copyright 2009, John Wiley & Sons, Inc. Hypothalamus Hypothalamus is a section of brain above where pituitary gland is suspended from by infundibulum or stalk Hypothalamus is a major link between nervous and endocrine system It receives input from cortex, thalamus, limbic system & internal organs Is influenced by emotions and the metabolic state of the individual Copyright 2009, John Wiley & Sons, Inc.

Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings

Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence Hypothalamus controls pituitary gland with 7 different releasing & inhibiting hormones

Hypothalamus and anterior pituitary

Flow of Blood to Anterior Pituitary Controlling hormones enter blood Travel through portal veins Enter anterior pituitary at capillaries

Hypothalamic control of anterior pituitary secretions

Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence Hypothalamus controls pituitary gland with 7 different releasing & inhibiting hormones

Endocrine Control: Three Levels of Integration Figure 7-13: Hormones of the hypothalamic-anterior pituitary pathway

Hypothalamus Releasing Hormones: Secretion Synthesizes hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence Hypothalamus controls pituitary gland with 7 different releasing & inhibiting hormones

Hypothalamic control of anterior pituitary Effect on Ant Pituitary Hormones (+) TSH & Prolactin Thyrotropin-releasing hormone (TRH) 1. (+) ACTH Corticotropin-releasing hormone (CRH) 2. (+) GH Growth hormone releasing hormone (GHRH) 3. (+) Prolactin Prolactin releasing hormone (PRH) 4. (+) Gonadotropic hormones (LH, & FSH) Gonadotropin-releasing hormone (GnRH) 5. (-) Prolactin Prolactin inhibitory hormone (PIH) “Dopamine” 6. (-) GH (-) TSH Growth hormone inhibitory hormone (GHIH) “Somatostatin (SS)” 7.

Hypothalamic hormones Hypothalamus GnRH GHRH GHIH/SS TRH PRIH PRH CRH + + - - + + - + + FSH & LH GH TSH Prolactin ACTH Anterior Pituitary Copyright 2009, John Wiley & Sons, Inc.

Regulation of Ant. Pitutary Hormone Secretion negative feedback Hypothalamus Copyright 2009, John Wiley & Sons, Inc.

Negative Feedback Regulation Copyright 2009, John Wiley & Sons, Inc.

GHIH inhibits secretion of hGH by somatotrophs Low blood glucose (hypoglycemia) stimulates release of High blood glucose (hyperglycemia) hGH GHRH stimulates secretion of hGH by GHIH GHRH hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly Blood glucose level rises to normal (about 90 mg/100 mL) If blood glucose continues to increase, hyperglycemia inhibits release of GHRH 1 6 7 3 4 5 2 GHIH inhibits secretion of hGH by somatotrophs Low blood glucose (hypoglycemia) stimulates release of High blood glucose (hyperglycemia) Anterior pituitary hGH GHRH stimulates secretion of hGH by GHIH GHRH A low level of hGH and IGFs decreases the rate of glycogen breakdown in the liver and glucose enters the blood more slowly hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly Blood glucose level rises to normal (about 90 mg/100 mL) If blood glucose continues to increase, hyperglycemia inhibits release of GHRH 1 6 7 8 3 4 5 2 GHIH inhibits secretion of hGH by somatotrophs Low blood glucose (hypoglycemia) stimulates release of High blood glucose (hyperglycemia) Anterior pituitary hGH GHRH stimulates secretion of hGH by GHIH GHRH A low level of hGH and IGFs decreases the rate of glycogen breakdown in the liver and glucose enters the blood more slowly Blood glucose level falls to normal (about 90 mg/100 mL) hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly rises to normal If blood glucose continues to increase, hyperglycemia inhibits release of GHRH 1 6 7 8 9 3 4 5 2 GHIH inhibits secretion of hGH by somatotrophs Low blood glucose (hypoglycemia) stimulates release of High blood glucose (hyperglycemia) Anterior pituitary hGH GHRH stimulates secretion of hGH by GHIH GHRH A low level of hGH and IGFs decreases the rate of glycogen breakdown in the liver and glucose enters the blood more slowly Blood glucose level falls to normal (about 90 mg/100 mL) hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly rises to normal If blood glucose continues to increase, hyperglycemia inhibits release of GHRH continues to decrease, hypoglycemia inhibits release of GHIH 1 6 7 8 9 10 3 4 5 2 Low blood glucose (hypoglycemia) stimulates release of High blood glucose (hyperglycemia) hGH GHRH stimulates secretion of hGH by somatotrophs GHIH GHRH hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly Blood glucose level rises to normal (about 90 mg/100 mL) If blood glucose continues to increase, hyperglycemia inhibits release of GHRH 1 6 3 4 5 2 Anterior pituitary Low blood glucose (hypoglycemia) stimulates release of hGH GHRH stimulates secretion of hGH by somatotrophs GHRH hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly Blood glucose level rises to normal (about 90 mg/100 mL) If blood glucose continues to increase, hyperglycemia inhibits release of GHRH 1 3 4 5 2 Anterior pituitary Low blood glucose (hypoglycemia) stimulates release of hGH GHRH stimulates secretion of hGH by somatotrophs GHRH 1 2 Low blood glucose (hypoglycemia) stimulates release of hGH GHRH stimulates secretion of hGH by somatotrophs GHRH hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly 1 3 2 Low blood glucose (hypoglycemia) stimulates release of hGH GHRH stimulates secretion of hGH by somatotrophs GHRH hGH and IGFs speed up breakdown of liver glycogen into glucose, which enters the blood more rapidly Blood glucose level rises to normal (about 90 mg/100 mL) 1 3 4 2 Low blood glucose (hypoglycemia) stimulates release of GHRH 1