Exam 3: Ch 19 Regulation of Metabolism Flashcards
Pancreatic Islets of Langerhans
- Contain 2 cell types involved in energy homeostasis:
- a cells
- b cells
a cells
- secrete glucagon
- when glucose levels are low,
- causes increased glucose by stimulating glycogenolysis in liver
b cells
- secrete insulin
- when glucose levels are high
- reduces blood glucose by promoting its uptake by tissues
Normal fasting glucose level
65–105 mg/dl
After a meal is absorbed, blood glucose levels
- rise to ~ 140 – 150 mg/dl
- This rise stimulates secretion of insulin and inhibits glucagon secretion
Insulin & glucagon normally prevent
levels from rising above 170mg/dl after meals or falling below 50mg/dl between meals
Insulin Overall effect is to promote
anabolism
anabolism
- Promotes storage of digestion products (not only glucose)
- Inhibits breakdown of fat & protein
- Inhibits secretion of glucagon
Insulin: Anabolism stimulates
insertion of GLUT4 transporters (transport by facilitated diffusion) in cell membrane of skeletal muscle, liver, & fat
Oral Glucose Tolerance Test
- Assesses ability of b cells to secrete insulin & insulin’s ability to lower blood glucose
- Responses to drinking a glucose solution are measured
Oral Glucose Tolerance Test
in non-diabetics
glucose levels return to normal within 2 hrs
Oral Glucose Tolerance Test
in diabetics
Diabetes mallitus causes blood glucose >200 mg/dl after 2 hrs
Glucagon
- Maintains blood glucose concentration above 50mg/dl
- Stimulates glycogenolysis in liver
- Stimulates gluconeogenesis, lipolysis, & ketogenesis
- Skeletal muscle, heart, liver, & kidneys use fatty acids for energy
Effects of ANS on Insulin & Glucagon
ANS innervates islets
Activation of parasympathetic NS
stimulates insulin secretion
Activation of sympathetic NS
NS stimulates glucagon & inhibits insulin
Effects of Intestinal Hormones
Insulin levels increase more rapidly after glucose ingestion than after intravenous glucose infusion
after intravenous glucose infusion
due to hormones secreted by intestine during meals
- “in anticipation” of glucose rise: all stimulate insulin secretion
- GIP; GLP-1; CCK
GIP
= gastric intestine peptide (secreted by duodenum),
GLP-1
= glucagon-like peptide (secreted by ileum),
CCK
= cholecystokinin
Diabetes mallitus
characterized by chronic high blood glucose levels (hyperglycemia)
hyperglycemia
the major cause of kidney failure and amputations, and is the 2nd leading cause of blindness
Type I (insulin dependent or IDDM)
- due to insufficient insulin secretion by beta cells
- 5 – 10% of total cases
- requires exogenous insulin
Type II (insulin independent or NIDDM)
- due to lack of efficiency of insulin at target cells
- 90 – 95% of total cases
Type 1diabetes (formerly “juvenile on set”)
= b cells of islets are destroyed by autoimmune attack, thus beta cells secrete little or no insulin
Glucose is unable to enter resting muscle or adipose cells
–> rate of fat synthesis lags behind rate of lipolysis –> fatty acids are converted to ketone bodies, leading to ketosis (↑ [ketone] in blood) producing ketoacidosis (↓ pH) –> glucose and ketones in urine (glucosuria or ketonuria) + ↑ H2O excretion because glucose and ketones act like osmotic diuretics (severe dehydration)
–> ↑ glucagon levels stimulate
glycogenolysis in liver, which ↑ [glucose] in blood also ↑ [ketone] in blood–>serious electrolyte imbalances–> coma or death
Type II diabetes
due to lack of efficiency of insulin at target cells)=
Type II diabetes slow to develop
heredity plays a role and occurs most often in overweight people
Type II diabetes involves
insulin resistance; usually accompanied by normal-to-high insulin levels
Type II diabetes treatable by
- exercise & diet
- b/c being over weight causes insulin resistance, thus ↑ caloric expenditure and shrinking fat cells ↑ insulin responsiveness
- Is not usually accompanied by ketoacidosis
Hypoglycemia
abnormally low blood [glucose]
Reactive hypoglycemia
is over secretion of insulin due to an exaggerated response of cells to a rise in glucose
Hypoglycemia
occurs in
people who are genetically predisposed to type II diabetes
Hypoglycemia controlled by
eating less carbohydrates and eating many small meals throughout the day
Hypoglycemia symptoms
include tremors, hunger, weakness, blurred vision, & confusion
Anabolic effects of insulin are antagonized by
Glucagon
(catecholamines) epinephrine and norepinephrine are made by
the adrenal medulla in response to sympathetic innervation
The actions of epinephrine and norepinephrine are similar to
- glucagon,
- stimulating glycogenolysis (release of glucose from liver), & lipolysis (release of fatty acids from adipose)
Adrenal Hormones - Metabolic Effects of Epinephrine & Norepinephrine
- glucagon is released during
- fasting to ↑ blood [glucose] and during the flight or flight response,
- epinephrine and norepinephrine are released to ↑ blood [glucose]
cortisol (a glucocorticoid) is made by
the adrenal cortex in response to sympathetic innervation
Cortisol is secreted
response to ACTH from Ant. Pit.
ACTH is often released in
response to stress, including fasting & exercise where it supports effects of glucagon
Cortisol promotes
lipolysis, ketogenesis, & protein breakdown (in muscles) –> Protein breakdown increases amino acid levels for use in gluconeogenesis in liver
Thyroid secretes mostly
inactive tetraiodothyronine (thyroxine =T4 in response to TSH from Ant. Pit.
basal metabolic rate = BMR is determined by
physical activity, eating, and HEAT
T3 helps set BMR by
- regulating cell respiration and heat;
- also necessary for growth & development, especially of CNS
T3 produces
uncoupling proteins (like those in brown fat) so↓ [ATP] controls BMR b/c stimulates heat production via [ATP] ↓, cellular respiration ↑, thus thyroxine ↑ metabolic heat (calorigenic effect)
BMR is essential for
cold adaptation
Growth Hormone (GH) Secretion - GH (somatotropin) is from
Ant. Pit.
stimulated by ↓ blood [glucose] and ↑ [aa] via GHRH (from hypothalamus)
GH (somatotropin) stimulates
growth in children & adolescents
GH (somatotropin) Has important metabolic effects in adults
- is increased during fasting
- stimulates protein synthesis
- stimulates fat breakdown
- decreases glucose use by most tissues b/c of ↓ rates of glycolysis due to ↑ lypolysis
Insulin-like Growth Factors (IGFs)
IGFs are similar to pro-insulin
produced by many tissues
Insulin-like Growth Factors (IGFs)
are called
somatomedins because mediate many of GH’s effects
Insulin-like Growth Factors (IGFs) examples
- Ex. Liver produces & secretes IGF-1 in response to GH; IGF-1 in turn stimulates cell division & growth of cartilage
- These actions are supported by IGF-2 which has more insulin-like actions
Parathyroid hormone, 1,25-dihydoxyVit D, & calcitonin control
- Ca2+ and P043- (phosphate) levels & activities
- via effects on bone formation & reabsorption, intestinal absorption, & urinary excretion
Skeleton is a storage reservoir for
for Ca2+ & PO43-
Bone is hardened with
calcium phosphate crystals (hydroxyapatite)
Osteoblasts
make bone in response to calcitonin
Osteoclasts
resorb bone in response to PTH
Parathyroid Hormone (PTH) and Bone - PTH is secreted by
by parathyroid glands
- is most important hormone in control of Ca2+ levels
PTH release is stimulated by
low blood Ca2+ levels
PTH stimulates
- Stimulates osteoclasts to reabsorb bone
- Stimulates kidneys to reabsorb Ca2+ from filtrate, & inhibits reabsorption of P043-
PTH Promotes formation of
1,25 Vit D3
Many cancers secrete
PTH-related protein that interacts with PTH receptors producing hypercalcemia
hypocalcemia
- Too little PTH
- causes tetanus b/c it increases membrane permeability to Na+
- over excitation of neurons and muscle fibers
Calcitonin
- secreted by C cells of thyroid gland
- works with PTH & 1,25 Vit D3 to regulate blood Ca2+ levels
Calcitonin stimulated by
increased plasma Ca2+
Calcitonin Inhibits
activity of osteoclasts
Calcitonin stimulates
- urinary excretion of Ca2+ & P043- by inhibiting reabsorption
- Physiological significance in adults is not understood
Estrogen, Testosterone, & Bone
- Estrogen causes
epiphyseal discs (cartilaginous growth plates) to seal (ossify) which stops growth (in both men and women)
Estrogen is made in
in ovaries (women) and in the epiphyseal discs from circulating testosterone (men)
Estrogen is necessary for
- is necessary for proper bone mineralization
- is necessary for prevention of osteoporosis
post menopausal women have ↓ [estrogen] b/c
↓ ovarian action but men can make it in bone
Estrogen stimulates
osteoblast activity & suppresses formation of osteoclasts
TSH & Thyroxine
- Hyperthyroids are more prone to
- osteoporosis
- Not well understood, but osteoblasts & osteoclasts have receptors for T3
1,25 Vitamin D3 Synthesis begins in
skin in response to by sunlight and continues in the kidneys, where cholesterol derivative is converted to Vit D3
1,25 Vitamin D3 Synthesis stimulated by
PTH
1,25 Vitamin D3 directly stimulates
intestinal absorption of Ca2+ & P043-, when Ca2+ intake is inadequate, directly stimulates bone resorption
1,25 Vitamin D3 stimulates kidney to
reabsorb Ca2+ and P043; simultaneously raising Ca2+ & P043- results in increased tendency of these to precipitate as hydroxyapatite
Inadequate Vit D in diet & body causes
osteomalacia (adults) & rickets (children) = loss of bone calcification
