Blood Sugar Regulation (week 1)

Question 1

Glucose

Answer 1

“preferred” and primary fuel source

“preferred” = glucose is more readily converted into energy in the mitochondria (proteins and fats require more steps/energy to make ATP)

Question 2

Glucose Dysregulation

Answer 2

supply and utilization are out of balance

associated with chronic conditions such as cancer, stroke, heart disease, abnormal cholesterol, and alzheimer’s

in 2017 1 in 4 healthcare dollars spent ($327 billion) on type 2 diabetes

Question 3

carbohydrate classification

Answer 3

classified according to:
-the number of sugar units in chain
-types of bonds that hold the sugars together in their chains

simple:
-monosaccharides
-disaccharides

complex:
-oligosaccharides
-polysaccharides

Question 4

simple carbohydrates: monosaccharides

Answer 4

one sugar unit

building block of all other types of carbohydrates

Glucose:
-primary sugar in many complex carbs like starch
-free form found in fruits and some sweeteners

Fructose:
-fruits, veggies, honey
-sweetest of simple sugars
-large amounts can impose an outsized burden on the body

Galactose:
-released through the digestion of milk sugar
-converted to glucose in the liver

Question 5

simple carbohydrates: disaccharides

Answer 5

sucrose:
-table sugar
-composed of one glucose and one fructose
-rich in beets and sugar cane

lactose:
-composed of one glucose and one galactose
-dairy products (low in fermented dairy)

maltose:
-composed of two glucose
-found in cereal grains
-formed in the digestive tract from starch
-malt products (malt syrup and maltodextrin)

Question 6

complex carbohydrates

Answer 6

oligosaccharides
-three to ten sugar units
-legumes, bananas, artichokes
-formed in digestive tract due to polysaccharide breakdown
-some are indigestible

polysaccharides:
-over ten sugar units
-starch, fiber, and glycogen

Question 7

complex carbs: polysaccharides

Answer 7

Starch:
-composed of many linked glucose molecules
-two main types: amylose (straight) and amylopectin (branched)
-resistant starch - undigestible, acts as prebiotic
-green bananas, legumes, boiled & cooled potatoes, rice

Fiber:
-soluble and insoluble are undigestible
-composed of monosaccharides and other molecules
-cellulose is made of glucose, but does not contribute to our blood glucose levels

Glycogen:
-quick access form of glucose storage
-muscle and liver

Question 8

digestion of carbohydrates

Answer 8

monosaccharides do not require digestion

other carbs:
Mouth:
-salivary amylase begins starch breakdown

Stomach:
-amylase inactivated by acidic environment
-mechanical breakdown continues

Small Intestine:
-pancreatic and brush border enzymes break starch into oligo and disaccharides
-specific enzymes break down disaccharides
-sucrase: sucrose –> 1 glucose + 1 fructose
-maltase: maltose –> 2 glucose
-lactase: lactose –> 1 glucose + 1 galactose

Large Intestine:
-bacterial metabolism
-eliminated in stool

Question 9

absorption of carbohydrates

Answer 9

Small Intestine:
-single monosaccharides transported to liver via the hepatic portal vein

Liver:
-converts galactose to glucose
-intestines and liver convert fructose to glucose, but some amount enters circulation
-glucose is converted to storage forms or sent into the bloodstream

Question 10

ATP: the energy of life

Answer 10

metabolism:
-utilization, conversion, and storage of fuel to create and control biological energy
-mitochondria convert fuel into ATP to perform work
-numerous metabolic pathways = flexibility to thrive in changing circumstances

fuel moves in two main directions:

STORING fuel when supplies are high (fed state)

RELEASING stored fuel when supplies are low (fasted state or macronutrient restriction)

Question 11

Glycolysis

Answer 11

fed state pathway

glucose is converted into 2 pyruvate molecules in cytoplasm (some ATP is created)

pyruvate goes to mitochondria and is converted to acetyl CoA

acetyl CoA enters the citric acid cycle

citric acid cycle and electron transport chain release more ATP

oxygen is required

goal = break down the elemental bonds in glucose to release energy in a controlled way

Question 12

balancing glycogen / fat storage

Answer 12

glycogenesis:
-convert glucose to glucogen and store it in the liver or skeletal muscles
-skeletal muscles hold ~500g, liver holds ~100g
-1 gram glycogen = 4 calories
-max 2,400 calorie reserve = limited fuel storage

Lipogenesis:
-after liver and muscles are full, convert excess glucose into fatty acids and triglycerides for storage in adipose tissue
-1 gram fat = 9 calories
-adipose tissue expands = extensive storage

refueling = glycogen reserves first, then fat storage

the body can convert glucose into fatty acids during lipogenesis, but the body can NOT convert fatty acids into glucose

Question 13

storing surplus fuel

Answer 13

fed state: ample amounts of glucose available for cellular energy

two main ways to store surplus fuel:

Glycogensis: converts glucose to glycogen (animal polysaccharide) and stores it in the liver and skeletal muscles

Lipogenesis: converts glucose into fatty acids and triglycerides and stores it in the adipose tissue

Question 14

glycogenesis and glycogenolysis

Answer 14

Glycogensis:
-“glycogen-generating”
-fed state - STORE
-creation of the polysaccharide glycogen from glucose (liver and muscle)

Glycogenolysis:
-glycogen “cutting”
-fasted state - RELEASE
-low glucose supply and/or high energy demand
-keeps a stable blood glucose level between meals
-fast acting, explosive fuel
-glycogen stores are “muscle sparing”

Question 15

lipogenesis

Answer 15

-“lipid generating”
-fed state: STORE
-increases when glycogen stores are full
-the synthesis or production of new fatty acids and triglycerides from non-fat sources (glucose or amino acids)
-occurs primarily in the liver and adipose tissue during fed state (STORE)

De novo lipogenesis:
adipose tissue uptakes glucose directly and converts to triglycerides for storage

body fat = offers more energy storage in less space

Question 16

Lipolysis

Answer 16

“lipid cutting”

fasting state: RELEASE

occurs when blood glucose levels and glycogen stores are depleted (fasting, exercise, or energy deficient)

blocked by insulin

similar to glycolysis - but the enzymes and substrates are different:
1. hormonal cues activate lipase enzymes to release fatty acids
2. fatty acids are taken up by cells for fatty acid oxidation (beta-oxidation)
3. fatty acids are turned to acetyl-CoA (rather than pyruvate as we saw in glycolysis)
4. Acetyl-CoA enters the citric acid cycle and electron transport chain to release ATP

note: fatty acids DO NOT convert back into glucose

Question 17

lipolysis vs glycolysis

Answer 17

beta oxidation:
-provides more ATP per unit of fuel than sugars
-requires more oxygen to produce an equivalent amount of ATP compared to glycolysis
-takes longer to produce energy
-inhibited by insulin

which do we use first?

deplete glycogen stores first in a fasted state or during exercise

glycogenolysis and lipolysis are not mutually exclusive:
-use more glycogen while working
-use more fatty acids while resting

Question 18

ketosis

Answer 18

closely related but distinct from fatty acid beta oxidation:

fatty acid beta-oxidation:
-breakdown of fatty acids into acetyl-CoA molecules
-can happen between meals, short fasts, exercise

ketosis:
-a metabolic state in which the body primarily relies on ketone bodies for energy

ketone bodies:
-byproducts of fatty acid breakdown
-surplus acetyl-CoA goes to liver and is converted into ketone bodies
-acetoacetate, beta-hydroxybutyrate, and acetone
-can be used by various tissues, including the brain, as an alternative source of energy

Question 19

gluconeogenesis / protein catabolism

Answer 19

gluco = glucose
neo = new
genesis = generate

reserved for time of high dietary protein intake, low carbohydrate

fasted state: RELEASE

protein spared for building and repair

primary steps:
1. proteins broken down into amino acids
2. deamination: the amino group (nitrogen) is removed from the amino acids, leaving carbohydrate-like skeleton
3. carbon skeletons are converted into glucose

more energy-intensive process than glycolysis

spend more energy to make energy = weight management

fasting state = beneficial breakdown of damaged proteins

starvation state = catabolize functional proteins in the body

Question 20

gluconeogenesis / lactate

Answer 20

lactate = metabolic byproduct when glucose is broken down in a low-oxygen environment (anaerobic metabolism)

aerobic metabolism = use of oxygen in glycolysis and cellular respiration

anaerobic metabolism = intense exercise depletes oxygen supply
-lactate is produced in the muscle cells, transported to the liver where it is converted into glucose and sent back out into the bloodstream

Question 21

gluconeogenesis / glycerol

Answer 21

produced from the breakdown of triglycerides in adipose tissue

triglycerides = three fatty acid molecules + one glycerol molecule

lipolysis liberates stored lipids for fuel:
-fatty acids –> fatty acid beta oxidation
-glycerol –> liver to be converted into an intermediate compound that can enter glycolysis in the mitochondria

glycerol = substrate for glycolysis in the brain during prolonged fasting

Question 22

fructolysis

Answer 22

the metabolism of dietary fructose to produce energy

shares many enzymes and substrates as glycolysis, but has key differences:
-glucose can be taken up by cells throughout the body
-fructose is limited to two pathways:
-primary pathway = liver (vast majority)
-limited uptake in muscle and adipose tissue

excessive amounts place an added burden on the liver and cause an increase in triglycerides compared to glucose metabolism

Question 23

metabolic flexibility

Answer 23

carbs = KINDLING
-burn fast and hot
-quickly depleted
-short, intense activity

fats = LOGS
-burn more slowly than kindling
-produces more net ATP than glycolysis
-requires more time and oxygen
-stable supplies
-slow, long, low intensity activity

metabolic flexibility:
-the capacity for an organism to adapt fuel utilization to fuel availability
-shift between fuel sources based on our circumstances
-excess fuel, in either form, can negatively impact our metabolic health (insulin resistance)

Question 24

summary of terms

Answer 24

lysis = break down
genesis = create

response to LOW circulating glucose supply:
-glycogenolysis = break down stored glycogen for use = increase blood glucose

gluconeogenesis = create new glucose from non-carbohydrate sources = increase blood glucose

lipolysis = break down stored lipids = use alternative fuel

response to HIGH circulating glucose supply:
glycogenesis = create glycogen = lower blood glucose by moving into storage

lipogenesis = create fatty acids and triglycerides = lower blood glucose by moving into storage

Question 25

what are the primary regulators of blood sugar regulation?

Answer 25

the brain and autonomic system

hypothalamus = region of brain
pituitary gland = just below the hypothalamus

they are considered part of the endocrine system rather than the brain

bridge between endocrine system and nervous system

Question 26

Brain and ANS summary

Answer 26

hypothalamus:
-monitors blood glucose levels through specialized sensing neurons
-communicates needed changes in blood sugar to the pituitary gland

Pituitary:
-directs the activity of the PAALS
/indirectly via hormonal signals
/directly via efferent neurons of the autonomic nervous system
-glucose is low –> raises blood glucose by increasing conversion of stored fuel
-glucose is high –> lowers blood glucose by stimulating uptake, utilization, and storage of circulating glucose

if blood sugar regulation were an orchestra, the brain and autonomic nervous system would be the conductor, and the PAALS would be the instruments

Question 27

PAALS: Pancreas

Answer 27

Dual role

Exocrine (digestive): secretes enzymes and bicarbonate into the intestinal lumen
-exocrine is much larger than endocrine in terms of pancreas size / production

Endocrine (hormonal): produces hormones to regulate blood sugar levels and growth

pancreatic islets or islets of langerhans:
-1-2% of pancreas total mass
-receive 10-15% of pancreas’s blood flow
-contains two main cell types:
/alpha cells (produce glucagon
/beta cells (produce insulin)

Question 28

Insulin (pancreas)

Answer 28

what does insulin do?
-moves glucose from the blood stream into cells
-increases when blood sugar rises
-lowers when blood sugar declines (between meals or fasting)

How does insulin achieve this?
-docks on the cell membrane
-triggers a transport protein (GLUT protein) to come to the surface and act as a portal for glucose

Insulin = anabolic hormone (stimulates growth)
-promotes the synthesis of glycogen and structural proteins in muscle tissue
-inhibits the degradation of muscle protein in the body

Question 29

Glucagon (pancreas)

Answer 29

stimulates the breakdown (catabolism) of tissue

produced in alpha cells of pancreas

prompts the release of stored fuel when circulating glucose levels drop into lower range:

increase in glycogenolysis: turn glycogen into glucose
-in the liver, glucose is released into circulation
-in muscle, glucose is used in the cells of the muscle tissue (in situ)

increase in gluconeogenesis: turns proteins and other non-carbohydrate sources into glucose

increase in lipolysis: sends fatty acids to beta-oxidation pathway to produce energy

Question 30

counter-regulatory roles: glucagon and insulin

Answer 30

post meal, FED, glucose in upper range = increase insulin
-increase glucose uptake by cells (ATP)
-increase glycogenesis (storage)
-increase lipogenesis (storage)
-decrease lipolysis (inhibit release)

Pre-meal, FAST, glucose in lower range = increase glucagon
-increases glycogenolysis (release carb stores)
-increase gluconeogenesis (release protein stores)
-increase lipolysis (release fat stores)

insulin says STORE
glucagon says RELEASE

Question 31

PAALS: Adrenals

Answer 31

low blood sugar is an emergency - why?
-physical work in a fight or flight situation (requires glucose)
-blood sugar too low = pass out, risk for injury or death
-adrenals and glucagon keep glucose levels from falling too low

adrenal glands:

outer cortex:
-activated by pituitary gland in the HPA axis
-produces hormones that regulate blood pressure and sex characteristics
-produces cortisol: glucocorticoid steroid

inner medulla:
-produces catecholamine hormones:
-dopamine
-adrenaline (epinephrine)
-noradrenaline (norepinephrine)

Question 32

PAALS: adrenal hormones

Answer 32

all three stress hormones will increase the fuel availability:

-glycogenolysis: converts glycogen to glucose
-gluconeogenesis: converts non-carbohydrate sources into glucose
-lipolysis which releases fatty acids from triglycerides stored in body fat
-decrease insulin (stop storing) and increase glucagon (release fuel)

Cortisol:
-inducing insulin resistance in liver, adipose, and muscles
-acute doses = powerful anti-inflammatory
-chronically elevated = cells can become resistant –> loses anti-inflammatory effect
-inhibits digestion

adrenal hormones raise blood glucose levels

Question 33

PAALS: skeletal muscle

Answer 33

plays three key roles in blood sugar regulation:

1. glucose uptake and utilization
2. storing excess glucose as glycogen
   -350-500 grams of glucose
   -can only be used locally
3. providing protein for gluconeogensis
   -protein broken down via proteolysis and converted into glucose within the liver

Question 34

glucose uptake in skeletal muscle

Answer 34

skeletal and cardiac muscles take in glucose by:
-GLUT-4 transport proteins
-initiated when insulin binds to cell receptors
-GLUT 4 move from cytoplasm to membrane to allow glucose into cell

in muscle tissue, GLUT 4 proteins can also uptake glucose without insulin
-initiated by exercise through a contraction mediated pathway
-muscles contraction helps manage glucose levels, even in the context of insulin resistance

adrenal hormones:
-raise blood sugar
-cause insulin resistance
-GLUT4 insulin-independent uptake through exercise can circumvent stress induced insulin resistance in muscle tissue

Question 35

adipose tissue (PAALS)

Answer 35

loose connective tissue composed of adipocytes (fat cells)

adipocytes filled with triglycerides
-triglycerides = diet + synthesized in liver from glucose
-triglycerides = 3 fatty acids + 1 glycerol
-contain more energy than glycogen

stores fat in certain conditions:
-full glycogen stores
-high blood sugar levels
-high insulin levels

releases fat in certain conditions:
-depleted glycogen stores
-low blood sugar levels
-low insulin levels

acts as an endocrine gland (leptin)

Question 36

adipose tissue & adiponectin

Answer 36

adipocytes produce adiponectin

adiponectin:
-helps regulate glucose levels, lipid metabolism, and insulin sensitivity
-protective against obesity and type 2 diabetes:

-enhances insulin sensitivity
-suppress gluconeogenesis
-promotes the fatty acid beta oxidation in muscles
-reduces chronic low grade inflammation
-reduces appetite / increased satiety

Question 37

PAALS: Liver

Answer 37

glycogenesis = glucose –> glycogen

glycogenolysis = glycogen –> glucose

gluconeogenesis = protein –> glucose

ketogenesis = fatty acids into ketones

lipogenesis = glucose –> triglycerides

-monosaccharides (galactose and fructose) –> glucose

Question 38

PAALS summary

Answer 38

pancreas:
-insulin: decrease blood glucose (anabolic/store, build)
-glucagon: increase blood glucose (catabolic/release, breakdown)

Adrenals:
-cortisol: increase blood glucose (catabolic release, breakdown), primary blood sugar regulation
-adrenaline and noradrenaline: amplify cortisols effects, acute stress response

Adipose:
-decrease blood glucose (triglyceride storage)
-release lipids
-adiponectin and leptin: regulate appetite and metabolism

Liver:
-converts fuel types
-stores and releases glycogen

Skeletal muscles:
-decrease blood glucose (glycogen storage/glucose uptake)

Question 39

Incretins

Answer 39

hormones produced in the digestive tract

two primary incretins involved in blood sugar regulation

glucagon-like peptide-1 (GLP-1):
-produced in intestine in response to food
-decrease blood glucose after carbohydrate rich meals
-decrease glucagon secretion (reduces release of stored glycogen)
-slows gastric emptying

glucose dependent insulinotropic peptide (GIP):
-released from the small intestine
-increase insulin secretion
-increase fat storage in adipose tissue

GLP-1 and GIP related medications are used in managing type 2 diabetes and weight loss

Question 40

understanding blood sugar levels

Answer 40

we are not studying blood sugar levels in order to diagnose clients with a metabolic disease

measuring blood sugar levels:
-powerful educational tool (prophylactic = before disease states)
-identify the body’s response to specific foods & activities
-identify correlations between blood sugar levels and energy levels, sleep, mood, cognitive function, or changes in signs and symptoms

working with a client with prediabetes or type 2 diabetes:
-be more familiar and confident working with goals and special concerns identified by primary care provider
-better sense of when to refer someone to primary care provider

Question 41

measuring blood sugar levels

Answer 41

two ways to measure:

fasting blood glucose levels (FBG):
-before meals
-after at least 8 hours of not eating
-baseline measurement
-conventional “normal” level is under 100 mg/dL

Postprandial blood glucose:
-1-2 hours after a meal
-helps understand how the body responds to a meal
-conventional “normal” level is less than 140 mg/dL

“normal” levels are controversial:
-study 1: FBG above 96 mg/dL = more than 3x risk of developing type 2 diabetes compared to levels below 90 mg/dL
-study 2: FBG above 85 mg/dL = increased risk of heart disease compared to levels below 81 mg/dL

Question 42

hypoglycemia

Answer 42

hypoglycemia = too little glucose

approximately 70 mg/dL is considered hypoglycemic

symptoms include:
-brain fog
-irritability
-shakiness
-headaches
-paleness
-hunger
-nausea
-fatigue
-loss of focus
-lightheadedness
-anxiety

symptoms vary based on physiological conditioning to low or high glucose levels

low carb dieters ay normally have levels ~70,g/dL and will not feel hypoglycemic

Question 43

hyperglycemia

Answer 43

hyperglycemia = too much glucose

approximately 180-200 mg/dL is considered hyperglycemic

often seen in individuals suffering from type 1 or type 2 diabetes

early symptoms include:
-frequent urination
-increased thirst
-blurred vision
-weakness
-fatigue

progressive symptoms include:
-confusion
-nausea and vomiting
-shortness of breath
-loss of consciousness

factors contributing to elevated blood glucose levels:
-consuming excessive sugar and refined carbs
-chronic stress
-inadequate sleep
-environmental toxins
-genetics
-lifestyle

Question 44

ways to measure glucose

Answer 44

at-home finger prick glucometers
-affordable
-easily accessible
-require a finger-prick blood sample
-read serum glucose levels at one moment in time
-can connect to a smart phone to track readings

continuous glucose monitors:
-sensor inserted beneath skin
-measures glucose levels in interstitial fluid (continuous, real time)
-convenient: no blood sample and always on
-may help make more informed decisions throughout the day
-more expensive
-constant data stream may cause food anxiety/stress

both tests require some operational learning to produce accurate results

Question 45

hemoglobin A1c

Answer 45

what is hemoglobin A1c? (HbA1c)
-blood test that measures estimated average blood glucose levels over about 2-3 months
-formed when glucose in the bloodstream attaches to hemoglobin (protein in red blood cells)
-results expressed as a percentage - higher values indicating poorer glucose control

how is it used?
-diagnostic tool for diabetes
-monitoring tool to assess effectiveness of diabetes treatment plans
-to evaluate risk of developing diabetes

reading may appear higher than actual average in some cases:
-frequent blood sugar spikes
-health conditions which extend the life or slow the turnover rate of red blood cells (iron deficiency anemia)

Question 46

recap: healthy blood sugar regulation

Answer 46

insulin (+ incretins) help limit upper range
“use & store”

glucagon and adrenal hormones help limit lower range
“release storage”