Endocrine control of fuel metabolism, pancreatic hormones

Lecture 4

genesis

generation of something

neogenesis

generating something new from something differentl

lysis

breakdown

metabolism

all chemical reactions that occur within body cells

fuel metabolism

intermediary metabolism

includes reactions involving the degrading, synthesis, and transformation of the 33 classes of energy-rich organic molecules

3 classes of energy rich organic molecules

protein- amino acids

carbohydrate- monosaccharides (mainly glucose)

fat (triglycerides)- monoglycerides

digestion

process of breaking down large nutrient molecules (macromolecules) into smaller absorbable units that are transferred into the blood

anabolism

buildup or synthesis of larger organic macromolecules from small organic molecular subunits

requires ATP

anabolism reaction results in

manufacture of materials needed by the cell

the storage of excess ingested nutrients

catabolism

breakdown of large, energy-rich organic molecules within cells

2 levels of catabolism

hydrolysis of large cellular macromolecules into smaller units

oxidation of smaller subunits (such as glucose) to yield energy for ATP

energy storage

food intake is intermittent, requiring energy storage for use between meals

1st energy storage

excess circulating glucose is stored in liver and muscle as glycogen

1% of body energy content

primary energy reservoir

free fatty acids from fat that are stored as triglycerides in adipose tissue

77% of body energy content

2 month storage reservoir

secondary energy reservoir

amino acids are stored in muscle as proteins

22% of the body energy

liver

primary role in maintaining normal blood glucose levels

principal site for metabolic interconversions such as gluconeogenesis

adipose tissue

primary energy storage site

important in regulating fatty acid levels in the blood

muscle

primary site of amino acid storage

major energy user

brain

can only use glucose as an energy source

does not store glycogen

ketosis

ketone bodies are formed by ketogenesis when liver glycogen is depleted

substrates are fatty acids and some amino acids

hyperglycemic

too much

hypoglycemic

too little

brain for special metabolic needs

brain uses glucose as sole source of energy

emergencies- ketones

blood glucose 70-120mg/100mL

liver glycogen

major source of glucose for the brain

when depleted, amino acid and glycerol can be converted to glucose by gluconeogenesis

gluconeogenesis

convert amino acids and glycerol to glucose

fatty acids

cannot be converted to glucose by gluconeogenesis

can be used by other tissues to spare brain glucose

pancreas exocrine

99% of tissue

enzymes in digestion

pancreas endocrine

1% of tissue-islets

fuel metabolism

glucoregulation

endocrine cells

islets of langerhans

islets

highly vascularized with blood from islets draining into hepatic portal vein

pancreatic islet hormones

exert major action in the liver prior to entry into the system circulation

islets

highly innervated by para and symp NS

regulate glucose homeostasis during stress

B cells

60%

insulin

a cells

30%

glucagon

D cells

10%

somatostatin

same molecule as in the brain that inhibits growth hormone release

different sources and function

PP cells

<1%

pancreatic polypeptide

reduces appetite and food intake

insulin

2 chains (a and b)

connected by 2 disulfide bonds

released in response to glucose entry into B cells

half life 3-5 mins

catabolized in liver and kidney

insulin

synthesized as preproinsulin protein

processed to proinsulin

cleaved into insulin peptide and C-peptide

stored in secretory granules

C-peptide and proinsulin

longer half life

only catabolized by the kidney

pancreatic B cells

synthesizes and releases insulin in response to glucose

full of vesicles containing insulin and C-peptide

glucose arrives at the cell

it can pass through a glucose transporter (GLUT)

glucose is

oxidized

inc ATP

depolarizes B cell

allows Ca influx

Ca

causes exocytosis of the insulin-containing vesicles into the blood

insulin

acts upon receptors on target cells (liver, muscle, fat)

insulin receptors

member of receptor tyrosine kinase family

signals intracellularly via insulin receptor substrates that amplify the response

target cells

do not normally express GLUTs on their membranes

insulin causes

translocation of GLUTs to the plasma membrane to allow glucose to enter the cells

in the cells

glucose is converted to glycogen for storage

glucose uptake occurs via

GLUTs that are translocated to the cell membrane

reactions are prioritized to

lower blood [glucose']

stimulates

glycogenesis and lipogenesis

inhibits

gluconeogenesis and glycogenolysis

insulin causes

rapid translocation of GLUTs to cell surface

in fat with glucose uptake

insulin enhances fatty acid uptake

promotes triglyceride synthesis from fatty acids and glycerol

inhibits lipolysis

in muscle with glucose uptake

insulin facilitates uptake of amino acids

inc amino acid incorporation into proteins

inhibits protein degradation

proglucagon

made in pancreatic a cells

processed to the 29-amino acid glucagon

glucagon

half life 3-6 mins

metabolized in liver and kidney

mostly kidney

glucagon

opposes effects of insulin on glucose and fatty acids

glucagon

inc blood [glucose]

glucagon

inc blood [fatty acids]

both insulin and glucagon

are stimulated by high concentrations of amino acids

both act to lower [amino acids] in blood

eat a meal

inc glucose

inc insulin

dec glucagon

incretins

enteric hormones released during meals

enhance glucose-stimulated insulin secretion

synthesized in L-cells of intestine

from differential splicing of proglucoagon

GLP-1 and 2

GLP-1 and 2

oppose glucagon’s general effect on varbohydrate metabolism

GLP-1

inhibits appetite through actions in hypothalamus

GLP-1 receptors in the arcuate nucleus

carbohydrate metabolism

regulated by the balance of insulin and glucagon

dysregulation leads to hyperglycemia

low glucose levels

plasma insulin is suppressed

glucagon dominates

high glucose levels

insulin predominates

suppresses glucagon