Pituitary Hormones Flashcards
1
Q
What are the hormones of the anterior pituitary?
A
Human growth hormone (hGH)
Thyroid-stimulating hormone (TSH) or thyrotropin
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactin (PRL)
Adrenocorticotropic hormone (ACTH) or corticotropin
Melanocyte-stimulating hormone (MSH)
2
Q
What does human growth hormone (hGH) do?
A
It stimulates secretion of insulin-like growth factors (IGFs) that promote growth, protein synthesis.
3
Q
What does thyroid stimulating hormone (TSH) or thyrotropin do?
A
It stimulates synthesis and secretion of thyroid hormones by the thyroid
4
Q
What does follicle-stimulating hormone (FSH) do?
A
The ovaries initiate the development of oocytes and the testes stimulate testosterone production.
5
Q
What does luteinizing hormone (LH) do?
A
The ovaries stimulate ovulation and the testes stimulate testosterone production.
6
Q
What does prolactin (PRL) do?
A
It promotes milk secretion by mammary glands.
7
Q
What does adrenocorticotropic hormone (ACTH) or corticotropin do?
A
It stimulate glucocorticoid secretion by the adrenal cortex.
8
Q
What does melanocyte-stimulating hormone (MSH) do?
A
It has an unknown role in humans. But it is known to have a mild inflammatory impact as well as causes pigmentation in amphibians.
9
Q
What is Proopiomelanocortin (POMC)
A
It is a large protein that is cleaved into smaller proteins such as beta-endorphin, alpha-melanocyte stimulating hormone (MSH), adrenocorticotropic (ACTH) and others. The pituitary gland synthesizes POMC in response to a signal from the hypothalamus; the signal being corticotroponin-releasing hormone (CRH). The hypothalamus releases CRH in response to physiological stressors such as pain, as in the postoperative period. When the protein products of POMC cleavage accumulates in excess, they turn hypothalamic CRH production off - that is, feedback inhibition occurs.
10
Q
What is growth hormone?
A
- It is also known as somatotropin, and is a protein hormone of roughly 190 amino acids that is synthesized and secreted by cells called somatotrophs in the anterior pituitary.
- It is a major participant in control of several complex physiological processes, including growth and metabolism.
- It stimulates overall body growth by spurring target cells to grow in size and divide.
- It is also of interest as a drug used in both humans and animals.
11
Q
What are the direct effects of growth hormone?
A
- These are the result of growth hormone binding its receptor on target cells.
- Ex// Fat cells (adipocytes) have growth hormone receptors and growth hormone stimulates them to break down triglyceride (lipolysis) and suppresses their ability to take up and accumulate circulating lipids.
- (anti-insulin effects) such as increased lipolysis and increased glucose mobilization. The direct growth of promoting actions of GH include the induction of insulin resistance in peripheral tissues, it causes hyperglycemia.
12
Q
What are the indirect effect of growth hormone?
A
- These are primarily mediate by insulin-like growth factor-1 (IGF-1), a hormone that is secreted from the liver in response to growth hormone.
- A majority of the growth promoting effects of growth hormone is actually due to IGF-1 acting on its target cells.
- The indirect IGF-1 dependent growth-promoting actions of GH include: the induction of protein synthesis, increases muscle mass, cartilage and bone growth, DNA and RNA synthesis, and cell proliferation.
13
Q
What are the effects of growth hormone on growth?
A
- Growth is a complex process that requires coordinated action of several hormones. The major roles in growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1.
- IGF-1 stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth.
IGF-1 also appears to be the key player in muscle growth. If stimulates both the differentiation and proliferation of muscle cells. - It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
14
Q
What are the metabolic effects of growth hormone?
A
- Growth hormone has important effect on protein, lipid, and carbohydrate metabolism. In some cases, a direct effect on growth hormone has been clearly demonstrated, in others IGF-1 is thought to be a critical mediator.
- Protein metabolism: In general GH stimulates protein anabolism (synthesis) in many tissues. This effect reflects increased amino acid uptake and increased protein synthesis. (Builds muscle)
- Fat metabolism: GH enhances the use of fat by stimulating triglyceride breakdown. (Burns fat)
- Carbohydrate metabolism: Increases blood glucose - GH is one of many hormones that serves to maintain blood glucose within a normal range. GH is often said to have anti-insulin activity, because it suppresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhances glucose synthesis in the liver.
15
Q
How is growth hormone secretion controlled?
A
There are two primary controllers which are two hypothalamic hormones.
1. Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.
2. Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus.
Somatostatin inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose.
16
Q
How does IGF-1 inhibit growth hormone?
A
When there are high levels of IGF-1 in the blood, this leads to decreased secretion of growth hormone by directly suppressing the somatotroph, but also through stimulating the release of somatostatin from the hypothalamus.
17
Q
What happens if there is a deficiency of growth hormone or receptor defects?
A
This results in growth retardation or dwarfism. A growth hormone deficiency depends on the age of onset of the disorder. It can result from either a heritable or acquired disease.
18
Q
What is growth hormone deficiency (GHD) or hypopituitarism?
A
This occurs in children, who have a deficient pituitary gland that secretes an inadequate amount of growth hormone.
- GHD is characterized by a decrease in growth, delay in skeletal maturation and absence of other explanations for poor growth.
- Growth failure often is apparent by the end of the first year, and growth rates continue to slow during childhood.
- Children with GHD are normally proportioned for age, tend to be overweight for height and have prominent deposits of abdominal fat.
- Many affected patients do not undergo puberty at the appropriate age because of GHD.
19
Q
What is the treatment for GHD?
A
The patient will be treated with human growth hormone, the majority of children treated appropriately will reach genetically expected adult heights. Growth hormone therapy is given by injection, either daily or several times per week.
20
Q
What are the two disorders cause by an excessive secretion of growth hormone?
A
Giantism and Acromegaly
21
Q
What is giantism?
A
Giantism is result of excessive growth hormone secretion that begins in young children or adolescents. It is a rare disorder, usually resulting from a tumor or somatotropes.
22
Q
What is acromegaly?
A
Acromegaly results from excessive secretion of growth hormone in adults. The onset of this disorder is typically insidious. Clinically, an overgrowth of bone and connective leads to changes in appearance that might be described as having “coarse features”. The excessive growth hormone and IGF-1 also lead to metabolic problems, including glucose intolerance.
High exposure to GH produces gigantism in youth prior to epithelial fusion and acromegaly in adults.
23
Q
What are the treatments for excessive secretion of growth hormone?
A
- Somatostatin analogs
- Growth hormone receptor antagonist
24
Q
What is growth hormone receptor?
A
- GH-R belongs to class 1 cytokine receptor superfamily
- Binding the hormone realigns the subunits by rotation and closer opposition, resulting in juxtaposition of the catalytic domains of the associate tyrosine-protein kinase JAK2 below the cell membrane.
- This changes results in activation of JAK2 by transphosphorylation, the phosphorylation of the receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins as well as direct phosphorylation of target proteins.
25
What are the physiological effects of prolactin?
- Conventional way to look at prolactin is that its major target organ is the mammary gland, and it functions to stimulate mammary gland development and milk production.
- It is difficult to point to a tissue that does not express prolactin receptors.
- There have been several hundred different actions have been reported for prolactin in various species.
26
What are the two major roles of prolactin in milk production?
1. Prolactin induced alveolar growth of the mammary gland. Alveoli are the clusters of cells in the mammary gland that actually secrete milk.
2. Prolactin stimulates lactogenesis or milk production after giving birth. Prolactin, along with cortisol and insulin act together to stimulate transcription of the genes that encode milk proteins.
27
How does prolactin act in mammals?
- Prolactin appears to have stimulatory effects in some species on reproductive or maternal behaviors such as next building and retrieval of scattered young.
- Prolactin determine pelage characteristics in many mammals.
28
How does dopamine effect prolactin secretion?
Dopamine is secreted into portal blood by hypothalamic neurons, binds to receptors on lactotrophs, and inhibits both the synthesis and secretion of prolactin.
29
How does stimulation of the nipples and mammary gland, as occurs during nursing, lead to prolactin release?
This effect appears to be due to a spinal reflex arc that causes release of prolactin-stimulating hormones from the hypothalamus.
30
How does estrogen impact prolactin secretion?
Estrogen can also stimulate prolactin synthesis and secretion. Estrogen increases during late pregnancy, this increases prolactin secretion which prepares the mammary gland for lactation at the end of gestation.
31
Which peptides are considered as putative prolactin releasing factors (PRFs)?
Thyrotropin releasing hormone (TRH)
Vasoactive intestinal polypeptide (VIP)
Neurohypophysial hormones (oxytocin and vasopressin)
32
How does nursing affect women who breastfeed?
Women who breastfeed their children have a longer period of amenorrhea and infertility following delivery than women who do not breastfeed.
33
What is hyperprolactinemia?
Hyperprolactinemia is the excessive secretion of prolactin, it is a relatively common disorder in humans. The conditions has numerous causes, including prolactin-secreting tumors and therapy with certain drugs.
- When in women, it often leads to amenorrhea (lack of menstrual cycles) and galactorrhea (excessive or spontaneous secretion of milk)
- When in men, they often show hypogonadism with decreases sex drive, decreases sperm production and impotence, they also often show breast enlargement (gynecomastia), but they very rarely produce milk.
This disorder can be the result of antipsychotic drugs that target dopamine.
34
What is the prolactin receptor (PRL-R)?
PRL-R belonging to class 1 cytokine receptor superfamily.
Prolactin functions by binding cell-surface expressed prolactin receptors, initiating signaling cascades, primarily utilizing Janus kinase-signaling transduced and activator of transcription (JAK-STAT)
35
What are gonadotropins?
Luteinizing and Follicle Stimulating Hormones
- They are known as gonadotropins because they stimulate the gonads.
- In males they are the testes and in female they are the ovaries. These are not necessary for life, but essential for reproduction. These two hormones are secreted from cells in the anterior pituitary called gonadotrophs.
36
What are the psychological effects of gonadotropins?
Physiological effects of the gonadotropins are known only in the ovaries and testes.
Together they regulate many aspects of gonadal function in both males and females.
37
What is the role of luteinizing hormone?
In both sexes, LH stimulates secretion of sex steroids from the gonads, testosterone in males and estrogen in females.
38
What is the role of follicle-stimulating hormone?
FSH stimulates maturation of ovarian follicles. Administration of FSH to humans and animals induces "superovulation" or development of many mature follicles. FSH is also critical for sperm production in males.
39
What is hypogonadism?
Hypogonadism is when there is diminished secretion of LH and FSH, this can cause failure in gonadal function. Typically when this condition manifests in males, there is a failure to produce normal numbers of sperm; in females abnormal or absent reproductive cycles are commons observed.
40
What happens when there is an elevation of LH and FSH?
If there are elevated blood levels of gonadotropins, typically this is reflective of a lack of steroid negative feedback. Removal of the gonads from either males or females (a practice commonly done in domesticated animals) leads to a persistent elevation of LH and FSH.
In humans, excessive secretion of FSH and/or LH are most commonly the result of gonadal failure or pituitary tumors.
41
What does the posterior pituitary do?
- It does not synthesize hormones
- It stores and releases hormone made by the hypothalamus, which are transported along the hypothalamohypophyseal tract
- It stores and releases oxytocin and antidiuretic hormone.
42
What does oxytocin (OT) do?
- During and after delivery of a baby it will affect the uterus and breasts.
- Enhances smooth muscle contraction in the wall of the uterus.
Stimulates milk ejection from mammary glands.
43
What is oxytocin (OT)?
Oxytocin is a nine amino acid peptide that is synthesized in hypothalamic neurons and transported down axons of the posterior pituitary for secretion into the blood.
Oxytocin differs from antidiuretic hormone in two of the nine amino acids.
44
What are the physiological effects of oxytocin?
- Stimulation of milk ejection (milk letdown): Milk is initially secreted into small sacs within the mammary gland called alveoli, from which it must be ejected for consumption or harvesting. Mammary alveoli are surrounded by smooth muscle (myoepithelial) cells which are a prominent target cell for oxytocin. Oxytocin stimulates contraction of myoepithelial cells, causing milk to be ejected into the ducts and cisterns.
- OT stimulates uterine smooth muscle contraction at birth: At the end of gestation, the uterus must contract vigorously and for a prolonged period of time in order to deliver the fetus. During the later stages of gestation, there is an increase in abundance of oxytocin, which is associated with increased "irritability" of the uterus. Oxytocin is released during labor when the fetus stimulates the cervix and vagina, and it enhances contraction of uterine smooth muscle to facilitate parturition or birth.
45
What do Dr.'s give to stimulate birth?
Pitocin
46
What is the role of oxytocin in mammals?
It is involved in maternal behavior and pair bond formation.
47
How does oxytocin establish maternal behavior?
- Successful reproduction in mammals demands that mothers become attached to and nourish their offspring immediately after birth.
- The same events that affect the uterus and mammary gland at the time of birth also affect the brain.
During parturition, there is an increase in concentration of oxytocin in cerebrospinal fluid, and oxytocin acting within the brain plays a major role in establishing maternal behavior.
48
How is oxytocin secretion controlled?
The most important stimulus for release of hypothalamic oxytocin is initiated by physical stimulation of the nipples or teats. Also by mating and social interaction
- There are many factors that can inhibit oxytocin release, one of the being acute stress.
49
What hormone regulate water and ion balance?
Antidiuretic hormone (ADH): aka vasopressin
50
What does Antidiuretic hormone (ADH) aka vasopressin do?
- Decreases urine production by causing the kidneys to return more water to the blood.
- Also decreases water lost through sweating
- Causes constriction of arterioles which increases blood pressure (vasopressin)
Roughly 60% of the mass of the body is water, and despite wide variation in the amount of water taken in each day, body water content remains incredibly stable. Such precise control of body water and solute concentration is a function of several hormones acting on both the kidneys and vascular system, but there is no doubt that antidiuretic hormone is a key player in this process.
51
What are the physiological effect of antidiuretic hormone?
The single most important effect of antidiuretic hormone is to conserve body water by reducing the output of urine.
*A diuretic is an agent that increases the rate of urine formation (e.g. caffeine).
Injection of small amount of antidiuretic hormone into a person or animal results in antidiuresis or decreased formation of urine, and the hormone was named for this effect.
52
How does ADH work?
- Antidiuretic hormone binds to receptors in the distal or collecting tubules of the kidney and promotes reabsorption of water back into the circulation.
*In the absence of antidiuretic hormone, the kidney tubules are virtually impermeable to water, and it flows out as urine.
- ADH increase water reabsorption by stimulating insertion of "water channels" or aquaporins into the membranes of kidney tubules.
- These channels transport solute-free water through tubular cells and back into blood, leading to a decrease in plasma osmolarity and an increased osmolarity of urine.
53
What two situations cause diabetes insipidus (the most common disease of man and animals related to antidiuretic hormone)?
Hypothalamic ("central") diabetes insipidus - results from a deficiency in secretion of antidiuretic hormone from the posterior pituitary. Causes of this disease include head trauma, and infection or tumors involving the hypothalamus.
Nephrogenic diabetes insipidus - occurs when the kidney is unable to respond to antidiuretic hormone. Most commonly, this results from some type of renal disease, but mutation in the ADH receptor gene or in the gene encoding aquaporin - 2 have also been demonstrated in affected humans.
54
What happens if you have diabetes insipidus?
A major sign of either type of diabetes insipidus is excessive urine production. If there is adequate water available for consumption, the disease is rarely life-threatening, but withholding water can be very dangerous.
- Hypothalamic diabetes insipidus can be treated with exogenous antidiuretic hormone.
55
What are the adrenocortical hormones?
Adrenocorticotropic hormone (ACTH) from the pituitary stimulates the release of glucocorticoids from the adrenal cortex including cortisol, cortisone and corticosterone.
Basal output is regulated by negative feedback of glucocorticoids on ACTH at the pituitary and on Corticotrophin Releasing Hormone (CRH) at the hypothalamus.
56
What is the ACTH receptor?
The ACTH receptor, or MC2-R is expressed in the cortex of the adrenal glands, G protein-coupled receptor.
Regulated synthesis and release of glucocorticoids in response to release of ACTH by the pituitary.
ACTH also has long term effects on the growth and differentiation of the cells of the adrenal cortex.
57
How are the thyroid hormones released and controlled?
- TSH is regulated by hypothalamic releasing hormone, TSH-releasing hormone (TRH) or thyrotropin
- Thyroid hormones feedback to inhibit both TRH and TSH
- Stimulation of the hypothalamus by certain types of stress activate this system
- Low skin temperature stimulates the release of TRH from the hypothalamus
58
What are the functions of the hypothalamus?
- Autonomic nervous system regulation
- Hormone production
- Endocrine production
- Circadian rhythm regulation
- Limbic system interaction
- Various
- Temperature
- Feeding
59
What are the two types of cells of the Paraventricular Nucleus?
Parvocellular cells and Magnocellular cells
60
What are parvocellular cells?
Medially, they secrete hypothalamic releasing hormones, such as CRH.
Dorsally and ventrally, neurons project to the medulla and spinal cord to exert autonomic control. Some of these neurons secrete oxytocin and vasopressin, which can act as modulators.
61
What are magnocellular cells?
Two distinct populations control endocrine function by secreting oxytocin and vasopressin directly into the posterior pituitary.
62
How is oxytocin release and how does it impact lactation?
The supraoptic and paraventricular nuclei contain magnocellular neurons that secrete oxytocin in the general circulation in the posterior pituitary. When a baby sucks on a mother's nipples the mechanoreceptors are stimulated. These receptors activate neurons that project to the magnocellular hypothalamic neurons, causing those cells to fire brief bursts releasing oxytocin. Oxytocin, in turn, increases contraction of myoepithelial cells in the mamillary glands, leading to milk ejection.
63
How is vasopressin released?
Magnocellular neurons containing vasopressin are sensitive to changes in blood tonicity, releasing more vasopressin upon water loss. Vasopressin increases water resorption in the kidney. Transecting the neural inputs to the hypothalamus does not disrupt the ability to increase vasopressin release upon water loss. This finding confirms that the signal used by hypothalamic neurons is humoral, and not neural to modulate vasopressin release.
64
What hypothalamic pathways influence endocrine function?
- The hypothalamus secrete oxytocin and vasopressin into general circulation from nerve terminals ending in the posterior pituitary.
- The hypothalamus also secretes regulatory hormones into local portal circulation that drains into the anterior pituitary.
65
What are the hormones of the hypothalamus?
Thyrotropin-releasing hormone (TRH)
Somatostatin (SS)
Growth hormone releasing hormone (GHRH)
Gonadotropin releasing hormone (GnRH)
Corticotropin-releasing hormone (CRH)
Dopamine (DA)
66
What is TRH?
It is made from a larger pro TRH molecule that yields 5 TRH each.
The highest concentration is found in the paraventricular nucleus and the preoptic area of the hypothalamus.
Electrical stimulation of the PVN increases TRH in the portal vasculature.
It also stimulates TSH from the pituitary.
67
What is SS?
It is a peptide (14 amino acids in length) from a pheromone. It inhibits GH secretion.
68
What is GHRH?
It is a 44 amino acid peptide hormone - found in the arcuate and ventromedial hypothalamus (VMH).
69
What is GnRH?
It is a 10 amino acid long peptide hormone (decapeptide) - in rats mostly in the preoptic area of the hypothalamus. In humans it is found in the arcuate nucleus of the medial basal hypothalamus. It stimulates both LH and FSH secretion.
70
What is CRH?
It is a 41 amino acid peptide hormone, found in the parvocellular region of the PVN. It stimulates ACTH secretion.
71
What is dopamine?
It is a catecholamine and it inhibits PRL secretion.
72
How is TRH controlled?
cold skin temperatures
73
How is CRH controlled?
stress, exercise
74
How is DA controlled?
suckling inhibits DA
75
How is GHRH controlled?
Ghrelin from the gut
76
How is GnRH controlled?
multiple neurotransmitters from the brain (NE, GABA, glutamate)
77
What is the pancreas?
It is an elongated organ next to the first part of the small intestine. The endocrine pancreas refers to those cells within the pancreas that synthesize and secrete hormones.
78
What are the islets of Langerhans?
The endocrine potion of the pancreas takes the form of many small clusters of cells.
79
What are the two major cells types housed in the pancreatic islets?
Alpha cells (A cells)
Beta cells (B cells)
80
What do A cells do?
They secrete glucagon.
81
What do B cells do?
The produce insulin and are the most abundant of the islet cells.
82
What is insulin?
- Hormone of nutrient abundance
- A protein hormone consisting of two amino acid chains linked by disulfide bonds
- Synthesized as part of pro-insulin (86 AA) and then excised by enzymes, releasing functional insulin (51 AA) and C peptide (29 AA).
83
What is the structure of insulin?
1. Large polypeptide 51 AA (MW 6000)
2. Two chains linked by disulfide bonds
A chain (21 AA)
B chain (30 AA)
3 disulfide bonds
84
What happens in the pancreas?
- The pancreas synthesizes and secretes insulin and glucagon.
- Insulin signals the presence of high blood glucose.
- Glucagon signals the presence of low blood glucose.
85
What is the process of insulin secretion?
Insulin secretion in beta cells is triggered by rising blood glucose levels.
1. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose causes a rise in the ATP:ADP ratio.
2. This rise inactivate the potassium channel.
3. Causes the membrane to depolarize.
4. Causes the calcium channel to open up allowing calcium ions to flow inward.
5. The ensuring rise in levels of calcium leads to the exocytotic release of insulin from storage granules.
86
What are stimulants of insulin secretion?
- Increase in serum glucose
- Increase in serum amino acids
- Increase in serum fatty acids
- Increase in serum ketone bodies
87
What are the inhibitors of insulin secretion?
- Decrease in glucose
- Decrease in amino acids
- Decrease in free fatty acids
88
How is insulin secretion regulated?
- No insulin is produced when plasma glucose below 50 mg/dl
- Half-maximal insulin response occurs at 150 mg/dl
- A maximum insulin response occurs at 300 mg/dl
- Insulin secretion is biphasic:
~ Upon glucose stimulation - an initial burst of secretion (5-15 min.)
~ Then a second phase of gradual increment that lasts as long as blood glucose is high.
89
What happens when insulin is secreted?
The effects on insulin secretion when enough glucose is infused to maintain blood levels two to three times the fasting level for an house.
Almost immediately after the infusion begins, plasma insulin levels increase dramatically. This initial increase is due to secretion of performed insulin, which is soon significantly depleted.
The secondary rise in insulin reflects the considerable amount of newly synthesized insulin that is released.
Clearly, elevated glucose not only stimulates insulin secretion, but also transcription of the insulin gene and translation of its mRNA.
90
What is the insulin receptor and how does it work?
Tyrosine kinase
It functions as an enzyme that transfers phosphate groups from ATP to tyrosine residues on intracellular target proteins.
_--------______-------_____
91
What are the actions of insulin on cells?
Insulin is the hormone of abundance.
The major target for insulin are:
- Liver
- Kidney
- Skeletal muscle
- Adipose tissue
* The net result is fuel storage
92
What are the actions of insulin on carbohydrate metabolism?
Liver:
- Stimulate glucose oxidation
- Promotes glucose storage as glycogen
- Inhibits glycogenolysis
- Inhibits gluconeogenesis
Muscle:
- Stimulates glucose uptake (GLUT4)
- Promotes glucose storage as glycogen
Adipose tissue:
- Stimulates glucose transport into adipocytes
- Promotes the conversion of glucose into triglycerides and fatty acids
93
What is diabetes mellitus?
It is a serious disorder of carbohydrate metabolism.
It results from hyposecretion or hypoactivity of insulin.
The three main signs of DM are:
- Polyuria - huge urine outpui
- Polydipsia - excessive thirst
- Polyphagia - excessive hunger and good consumption
94
What is type I or insulin-dependent diabetes mellitus?
- Result of a deficiency of insulin. The onset of this disease typically is in childhood.
- It is due to destruction pancreatic B cells, usually the result of autoimmunity to those cells.
- Until the 1920s, when insulin was isolate, Type I diabetics usually died within a short time after onset of the disease.
- Many of the acute effects of this disease can be controlled by insulin replacement therapy, but inevitable, there are long-term adverse effects on blood vessels, nerve and other organ systems.
95
What is type II or non-insulin dependent diabetes mellitus?
- Begins as a syndrome of insulin resistance. That is, target tissues fail to respond appropriately to insulin.
- Typically, the onset of this disease is in adulthood. The nature of the defect has been difficult to ascertain - in some patients, the insulin receptor is abnormal, in other, one or more aspects of insulin signaling.
- Because there is not, at least initially, an inability to secret adequate amounts of insulin, insulin injections are not useful for therapy. Rather the disease is controlled through dietary therapy and hypoglycemic agents.
96
What is hyperinsulinemia or excessive insulin secretion?
- Usually the result of an insulin-secreting tumor. This condition is much less common than diabetes mellitus.
- The high levels of insulin resulting from this condition or from an overdose of insulin causes a precipitous drop in blood glucose concentration.
- The brain becomes starved for energy, leading to the syndrome of insulin shock which is acutely life-threatening.
97
What is glucagon?
A 29 amino acid polypeptide hormone that is a potent hyperglycemic agent.
Produced by alpha cells in the pancreas
Its major target is the liver, where is promotes:
- Glycogenolysis - the breakdown of glycogen to glucose
- Gluconeogenesis - synthesis of glucose from lactic acid and noncarbohydrates
- Release of glucose to the blood from liver cells
98
What is gluconeogenesis?
- If you haven't eaten recently and your live is low on glycogen, you start to catabolize fats and proteins.
- Some amino acids and the glycerol molecule from triglycerides can be used to make new glucose molecules in the liver-stimulated by glucagon.
- Glycerol part if triglycerides, lactic acid, and certain amino acids can be converted by the liver into glucose.
- Glucose formed from non-carbohydrate sources
- Stimulated by cortisol and glucagon
99
What happens if there is too much glucagon?
Insulin will dominate
- increase in glucose oxidation
- increase in glucose synthesis
- increase in fat synthesis
- increase in protein synthesis
100
What happens if there is too much insulin?
Glucagon will dominate
- Increase in glycogenolysis
- Increase in gluconeogensis
- Increase in ketogenesis
