The Endocrine Pancreas 1 and 2

Question 1

what equation can be used to calculate body energy?

Answer 1

Body energy = energy intake – energy output

Question 2

Energy (food) intake is the determined by the balance of activity in two hypothalamic centres, what are they?

Answer 2

Feeding Centre

Satiety Centre

Question 3

what does the Feeding Centre do?

Answer 3

promotes feelings of hunger and drive to eat

Question 4

what does the Satiety Centre do?

Answer 4

promotes feelings of fullness by suppressing the Feeding Centre

Question 5

Activity in each the fedding centre and satiety centrw is controlled by a complex balance of ______ and ________ signals as well as the presence of nutrients in plasma.

Answer 5

neural

chemical

Question 6

what is the Glucostatic theory?

Answer 6

food intake is determined by blood glucose: as [BG] increases, the drive to eat decreases (- Feeding Centre; + Satiety centre)

Question 7

what is the Lipostatic theory?

Answer 7

food intake is determined by fat stores: as fat stores increase, the drive to eat decreases (- feeding centre; + Satiety Centre). Leptin is a peptide hormone released by fat stores which depresses feeding activity

Question 8

what is leptin?

Answer 8

Leptin is a peptide hormone released by fat stores which depresses feeding activity

Question 9

Obesity results from disruption of what pathways

Answer 9

energy intake and energy output

Question 10

what is energy output?

Answer 10

Energy output describes all the processes we perform simply in order to stay alive, and those that we perform voluntarily, as well as the heat loss associated with these

Question 11

what are the 3 categories of energy output?

Answer 11

Cellular work

Mechanical work

Heat loss

Question 12

what cellular work contributes to energy output?

Answer 12

transporting molecules across membranes; growth and repair; storage of energy (eg. fat, glycogen, ATP synthesis)

Question 13

what mechanical work contributes to energy output?

Answer 13

movement, either on large scale using muscle or intracellularly

Question 14

what heat loss contributes to energy output?

Answer 14

associated with cellular and mechanical work accounts for half our energy output

Question 15

what is the only part of energy output that is voluntary?

Answer 15

Only part of energy output we can regulate voluntarily is mechanical work done by skeletal muscle

Question 16

Most common health advice provided by healthcare professional is what?

Answer 16

Eat less, exercise more!

Question 17

Metabolism =

Answer 17

integration of all biochemical reactions in the body

Question 18

whata re the 3 elements of metabolism?

Answer 18

1. Extracting energy from nutrients in food
2. Storing that energy
3. Utilising that energy for work

Question 19

what are anabolic pathways?

Answer 19

Build Up. Net effect is synthesis of large molecules from smaller ones, usually for storage purposes

build up and contribute to storage

Question 20

what are catabolic pathways?

Answer 20

Break Down. Net effect is degradation of large molecules into smaller ones, releasing energy for work

break down large molecules releasing energy power

Question 21

what is the anabolic phase?

Answer 21

After eating we enter an Absorptive State where ingested nutrients supply the energy needs of the body and excess is stored. This is an anabolic phase

Question 22

what is the catabolic phase?

Answer 22

Between meals and overnight the pool of nutrients in the plasma decreases and we enter a Post-absorptive State (aka Fasted State) where we rely on body stores to provide energy. This is a catabolic phase

Question 23

The Brain is an “obligatory ________ utiliser”!

Answer 23

glucose

Question 24

Why si it important to maintain BG in relation to the brain?

Answer 24

Most cells can use fats, carbohydrates or protein for energy but the brain can only use glucose (except in extreme starvation – see ketone production later), so in the post-absorptive state, even though no new carbohydrate is gained by the body we MUST maintain blood glucose concentration [BG] sufficient to meet the brain’s requirements

Question 25

Failure to maintain BG results in what and what may it lead to?

Answer 25

hypoglycaemia (low blood glucose) which can lead to coma and death

Question 26

how is BG maintained?

Answer 26

BG is maintained by synthesising glucose from glycogen (glycogenolysis) or amino acids (gluconeogensis)

Question 27

what is glycogenolysis?

Answer 27

glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting

Glycogenolysis occurs primarily in the liver and is stimulated by the hormones glucagon and epinephrine (adrenaline)

Question 28

what is gluconeogensis?

Answer 28

Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates

Question 29

what is the normal range of BG?

Answer 29

Normal range of [BG] = 4.2-6.3mM (80-120mg/dl)

****5 mmoles useful to remember****

Question 30

Hypoglycaemia = [BG] < _mM

Answer 30

Hypoglycaemia = [BG] < 3mM

Question 31

So, whatever you are eating or doing, [BG] is maintained over a fairly tight range. This is possible due to the actions of what two key endocrine hormones produced in the pancreas?

Answer 31

Insulin and Glucagon

Question 32

How much of the pancreas if endocrine and how much is exocrine?

Answer 32

99% of the pancreas operates as an exocrine gland releasing enzymes and NaHCO3 via ducts into the alimentary canal to support digestion

Only 1% of the pancreas has endocrine function. It’s hormones are produced in the Islets of Langerhans

Question 33

The Islets of Langerhans are scattered throughout the pancreas, 1-2 million islets, each with a copious blood supply

What are the 4 types of islet cells

Answer 33

a, b, d & F

Question 34

a cells of the Islets of Langerhans produce what?

Answer 34

GLUCAGON

Question 35

b cells of the Islets of Langerhans produce what?

Answer 35

INSULIN

Question 36

delta cells of the Islets of Langerhans produce what?

Answer 36

SOMATOSTATIN

Question 37

F cells of the Islets of Langerhans produce what?

Answer 37

F cells produce pancreatic polypeptide (function not really known, may help control of nutrient absorption from GIT.

Question 38

controls of blood glucose depend son the balance between what?

Answer 38

Depends on balance between insulin and glucagon

(not their actual concentration but the balance between the 2)

Question 39

what does more insulin that glucagon reuslt in?

Answer 39

Glucose taken up by cells from plasma ([BG] decreases)

Question 40

what does more glucagon that insulin reuslt in?

Answer 40

Glucose released into plasma from stores ([BG] increases)

Question 41

what is insulin?

Answer 41

Peptide hormone produced by pancreatic b cells

Stimulates glucose uptake by cells

Question 42

how is insulin made?

Answer 42

Synthesized as a large preprohormone, preproinsulin, which is then converted to proinsulin in the ER

Proinsulin is then packaged as granules in secretory vesicles. Within the granules the proinsulin is cleaved again to give insulin and C-peptide. Insulin is stored in this form until the b cell is activated and secretion occurs.

Question 43

During the _________ State glucose, amino acids (aa) and fatty acids enter blood from GI Tract. Both ________ and ___ stimulate _______ secretion but the major stimulus is ______ _____ ___________

Answer 43

During the Absorptive State glucose, amino acids (aa) and fatty acids enter blood from GI Tract. Both glucose and aa’s stimulate insulin secretion but the major stimulus is blood glucose concentration

Question 44

Insulin dominates during what state

Answer 44

the absorptive state

Question 45

what is the only hormone that lowers [BG]

Answer 45

insulin

Question 46

Most cells use ______ as their energy source during the _________ state. Any excess is stored as ________ in liver and muscle, and as __________ ____ in liver and adipose tissue

Answer 46

Most cells use glucose as their energy source during the absorptive state. Any excess is stored as glycogen in liver and muscle, and as triacylglycerols (TAG) in liver and adipose tissue

Question 47

what are amino acids used for?

Answer 47

Amino acids are used mainly to make new proteins with excess being converted to fat

Also form an energy source

Question 48

what are fatty acids stored as and where?

Answer 48

Fatty acids are stored in the form of triglycerides in adipose tissue and liver

Question 49

What is the mechanism of control of insulin secretion by [BG]?

Answer 49

b-cells have a specific type of K+ ion channel that is sensitive to the [ATP] within the cell = K_ATP channel

When glucose is abundant it enters cells through glucose transport proteins (GLUT) and metabolism increases. This increases [ATP] within the cell causing the K_ATP channel to close. Intracellular [K+] rises, depolarising the cell. Voltage-dependent Ca²⁺ channels open and trigger insulin vesicle exocytosis into the circulation

Question 50

why is insulin not released when BG is low?

Answer 50

When [BG] is low, [ATP] is low so K_ATP channels are open so K+ ions flow out removing +ve charge from the cell and hyperpolarizing it, so that voltage-gated Ca²⁺ channels remain closed and insulin is not secreted

Question 51

what is the primary action of insulin?

Answer 51

Binds to tyrosine kinase receptors on the cell membrane of insulin-sensitive tissues to increase glucose uptake by these tissues

Question 52

Insulin is the ONLY hormone that ______ ___

Answer 52

Insulin is the ONLY hormone that lowers [BG]

Question 53

what glucose transporters are there in muscle and adipose tissue and how do they work?

Answer 53

In muscle and adipose tissue, insulin stimulates the mobilization of specific glucose transporters, GLUT-4, which reside in the cytoplasm of these cells

When stimulated by insulin GLUT4 migrates to the membrane and is then able to transport glucose into the cell. When insulin stimulation stops, the GLUT-4 transporters return to the cytoplasmic pool

The glucose taken up by cells is primarily used for energy

Tyrosine kinase receptor so phosphorylate other proteins to switch things on and off and creates a cascade within the cell and one of the actions is causes exocytosis of vesicle and glut 4 to the membrane

Question 54

what are insulin dependant tissues?

Answer 54

adipose tissue

muscle

Question 55

Do tissues require insulin to take up glucose?

Answer 55

Most types of tissue do NOT require insulin to take up glucose, ONLY muscle and fat are insulin dependent

Question 56

______ and ___ make up a large proportion of the body

______ is » 40% BW and ____ 20-25% (in normality)

So a very large proportion of the body is ________ ___ ________ for its glucose uptake

Answer 56

muscle and fat make up a large proportion of the body

Muscle is » 40% BW and fat » 20-25% (in normality)

So a very large proportion of the body is dependent on insulin for its glucose uptake

Question 57

In other tissues glucose uptake is via other GLUT-transporters, which are NOT insulin-dependent

what are they? and where are they found?

Answer 57

GLUT-1 Basal glucose uptake in many tissues eg brain, kidney and red blood cells

GLUT-3 Similar

GLUT-2 b-cells of pancreas and liver

Question 58

is the liver insulin dependant?

Answer 58

The liver is not an insulin-dependent tissue. Liver takes up glucose by GLUT 2 transporters, which are insulin independent

Glucose enters down concentration gradient

Question 59

Is glucose transport in hepatocytes affected by insulin?

Answer 59

although insulin has no direct effect on the liver, glucose transport into hepatocytes is affected by insulin status

Question 60

How does insulin alter glucose transport in hepatocytes

Answer 60

picture 1 - In fed state, liver takes up glucose because insulin activates hexokinase which lowers [glucose]ic creating a gradient favouring glucose movement into the cells

picture 2 - In fasted state, liver synthesises glucose via glycogenolysis and gluconeogenesis, increasing [glucose]ic creating a gradient favouring glucose movement out of the cells into the blood

Question 61

additional actions of insulin:

how does insulin affect glycogen?

Answer 61

Increases glycogen synthesis in muscle and liver

Stimulates glycogen synthase and inhibits glycogen phosphorylase

Question 62

additional actions of insulin:

how does insulin affect amino acid uptake?

Answer 62

Increases amino acid uptake into muscle, promoting protein synthesis

Question 63

additional actions of insulin:

how does insulin affect protein synthesis?

Answer 63

Increases protein synthesis and inhibits proteolysis

Question 64

additional actions of insulin:

how does insulin affect triacylglycerol synthesis?

Answer 64

Increases triacylglycerol synthesis in adipocytes and liver i.e. stimulates lipogenesis and inhibits lipolysis.

Question 65

additional actions of insulin:

what eznymes does insulin inhibit in the liver?

Answer 65

Inhibits the enzymes of gluconeogenesis in the liver

Question 66

a) Increases glycogen synthesis in muscle and liver. Stimulates glycogen synthase and inhibits glycogen phosphorylase.
b) Increases amino acid uptake into muscle, promoting protein synthesis.
c) Increases protein synthesis and inhibits proteolysis
d) Increases triacylglycerol synthesis in adipocytes and liver i.e. stimulates lipogenesis and inhibits lipolysis.
e) Inhibits the enzymes of gluconeogenesis in the liver

all of the above are additional actions on insulin. what kind of processes are they?

Answer 66

All of the above are anabolic processes – laying down energy stores – or inhibit catabolism

Question 67

additional actions of insulin:

how does insulin interact with growth hormone?

Answer 67

Has a permissive effect of growth hormone (see GH lecture)

Insulin promotes action of growth hormone and growth hormone inhibits insulin

Question 68

additional actions of insulin:

how does insulin affect K+ ions?

Answer 68

Promotes K+ ion entry into cells by stimulating Na+/K+ ATPase. Very important clinically.***

Question 69

All these additional roles of insulin are possible because of what?

Answer 69

activation of multiple signal transduction pathways associated with the Insulin Receptor

Question 70

what is the process of insulin altering metabolism of a cell?

Answer 70

Question 71

how is insulin degraded?

Answer 71

Insulin has a half-life of around 5 minutes and is degraded principally in the liver and kidneys

Once insulin action is complete insulin-bound receptors are internalised by endocytosis and destroyed by insulin protease, some recycled

Question 72

image showing summary of all the effects of insulin

Answer 72

Question 73

what are all the stimuli which increase insulin release?

Answer 73

1. Increased [BG]*****
2. Increased [amino acids]plasma
3. Glucagon (insulin required to take up glucose created via gluconeogenesis stimulated by glucagon)
4. Other (incretin) hormones controlling GI secretion and motility eg gastrin, secretin, CCK, GLP-1, GIP. Released by ileum and jejunem in response to nutrients. Early insulin release prevents glucose surge when absorption occurs. Incretin hormones is the general terms for GI hormones – help stimulate the release of insulin prior to the glucose hitting the blood
5. Vagal nerve activity (see next slide) - same as GI hormones and anticipates you eating something and taking in glucose

Question 74

what stimuli inhibit insulin release?

Answer 74

1. Low [BG]
2. Somatostatin (GHIH)
3. Sympathetic a2 effects
4. Stress e.g. hypoxia - Stress results in reduced insulin recreation as you want the glucose in the blood readily available particularly to the brain

Question 75

Does vagal activity cause insulin release?

Answer 75

Vagal activity stimulates release of major GI hormones, and also stimulates insulin release

Question 76

How does insulin release differ when getting IV glucose comapred to oral glucose of the same amount?

Answer 76

Vagal activity stimulates release of major GI hormones, and also stimulates insulin release, therefore meaning that the insulin response to an intravenous glucose load is less than the equivalent amount of glucose administered orally, ie:

i.v. glucose leads to increased­ insulin by direct effect of ­glucose on b cells.

Oral loading of same amount of glucose leads to increased­ insulin by both direct effect on b cells and vagal stimulation of b cells, plus incretin effects!

Question 77

what is incretin?

Answer 77

a group of metabolic hormones that stimulate a decrease in blood glucose levels

Question 78

what type of hormone is glucagon and where is it produced?

Answer 78

Peptide hormone produced by a-cells of the pancreatic islet cells in same fashion as all peptide hormones

Question 79

what is the purpose of glucagon?

Answer 79

Primary purpose is to raise blood glucose

It is a glucose-mobilizing hormone, acting mainly on the liver

Question 80

how is glucagon degraded?

Answer 80

Plasma half-life 5-10mins, degraded mainly by liver

Question 81

Glucagon primarily opposes the action of ________, forming part of the glucose _________________ ________ ________ which includes the hormones epinephrine, cortisol and GH. It is most active in the _____________ state

Answer 81

Glucagon primarily opposes the action of insulin, forming part of the glucose counter-regulatory control system which includes the hormones epinephrine, cortisol and GH. It is most active in the post-absorptive state

Question 82

what are glucagons receptors?

Answer 82

G protein coupled receptors

Question 83

Glucagon receptors are G-protein coupled receptors linked to the adenylate cyclase/cAMP system which when activated phosphorylate specific liver enzymes resulting in what?

Answer 83

1. increased glycogenolysis (glycogen broken dowin into glucose)
2. increased gluconeogenesis (substrates: aa’s and glycerol (lipolysis)) - formation of glucose
3. formation of ketones from fatty acids (lipolysis)

All these processes occur in the liver

**** Net result is elevated [BG]****

Question 84

Summary picture:

Fasted-state metabolism must maintain plasma glucose for the brain

Answer 84

Question 85

Amino acids are also a potent stimulus for glucagon secretion. What would happen if it wasn’t?

Answer 85

hypoglycaemia

amino acids stimulate insulin release which in the abscene og glucagon would stimulate glucose uptake into cells, dramatically lowerin [BG]

potentially catastrophic for the brain

Question 86

increased glucose = increased­ insulin and decreased glucagon

decreased glucose = increased­ glucagon and decreased insulin

how do amino acids affect the release of insulin and glucagon?

Answer 86

Amino acids in the plasma stimulate release of both insulin and glucagon

This is an adaptation to adjust for the composition of a meal very high in protein (typical of carnivores!)

Question 87

How would a high protein meal with very little carbohydrate affect BG?

Answer 87

aas = increased­ insulin = decreased [BG]

aas = increased­ glucagon = increased ­ [BG]

aas = amino acids

Question 88

If it were not for the effect of aas on ________ then the insulin-stimulating effects of aas would result in very ____ [BG]. This is counteracted by the glucose mobilizing effects of glucagon and so [BG] is ___________

Answer 88

If it were not for the effect of aas on glucagon then the insulin-stimulating effects of aas would result in very low [BG]. This is counteracted by the glucose mobilizing effects of glucagon and so [BG] is maintained

Question 89

So, whatever you are eating or doing, the endocrine system is working to ensure that there is enough glucose circulating to supply the needs of the what?

Answer 89

brain = “obligatory glucose user”.

Question 90

What can other tissues use to produce energy apart form glucose?

Answer 90

Most other tissues can readily use FFAs and ketones to produce energy

Question 91

What happens in the post-absorptive state when there are lower insulin levels

Answer 91

In the post-absorptive state, lower insulin levels mean a large mass of tissue, i.e. muscle and fat, cannot readily access glucose and so there is glucose sparing for obligatory glucose users

Question 92

what are the stimuli that promote glucagon release?

Answer 92

1. Low [BG] (<5mM)
2. High [amino acids]. Prevents hypoglycaemia following insulin release in response to aa.
3. sympathetic innervation and epinephrine, b2 effect
4. cortisol
5. stress e.g. exercise, infection - Makes sure brain has adequate glucose to get you out of the stressful situation

Question 93

what are the stimuli that inhibit glucagon release?

Answer 93

1. glucose
2. free fatty acids (FFA) and ketones
3. insulin (fails in diabetes so glucagon levels rise despite high [BG] )
4. somatostatin - turns down insulin and glucagon

Question 94

how does increased parasympathetic activity affect insulin and glucagon?

Answer 94

increased parasympathetic activity (vagus) = increased­ insulin and to a lesser extent ­increased glucagon, in association with the anticipatory phase of digestion

Question 95

how does increased sympathetic activity affect insulin and glucagon?

Answer 95

increased sympathetic activation promotes glucose mobilization = increased­ glucagon, ­increased epinephrine and inhibition of insulin, all appropriate for fight or flight response.

Question 96

what 4 hormones make up the glucose counter-regulatory control?

Answer 96

glucagon

epinephrine

cortisol

GH

Question 97

what makes up the glucose counter-regulatory control and how is it done?

Answer 97

All act to raise BG

All do it by different ways

Question 98

What type of hormone is somatostatin (SS), what makes it and where

Answer 98

Peptide hormone, secreted by D-cells of the pancreas (and hypothalamus aka GHIH)

Question 99

what is the function of SS?

Answer 99

Main pancreatic action is to inhibit activity in the GI Tract

Function appears to be to slow down absorption of nutrients to prevent exaggerated peaks in plasma concentrations

Aka GHIH it inhibits secretion of GH from the anterior pituitary

Question 100

How is SS used clinically?

Answer 100

Synthetic SS may be used clinically to help patients with life-threatening diarrhoea associated with gut or pancreatic tumours

Question 101

Is SS an counter-regulatory hormone?

Answer 101

SS is NOT a counter-regulatory hormone

Question 102

How does SS affect insulin and glucagon?

Answer 102

SS is NOT a counter-regulatory hormone in the control of blood glucose but it does strongly suppresses the release of both insulin and glucagon in a paracrine fashion

Question 103

What happen when a patient has a pancreatic SS-secreting tumour?

Answer 103

Patients with pancreatic SS-secreting tumours develop the symptoms of diabetes which disappear when the tumour is removed

Question 104

A

Green – stimulatory process

Red – inhibitory processes

Answer 104

Low blood glucose

Question 105

B

Answer 105

Elevated plasma [aa]

Question 106

C

Answer 106

Elevated blood glucose

Question 107

how does exercise affect BG?

Answer 107

The entry of glucose into skeletal muscle is increased during exercise, even in the absence of insulin

There is an insulin-independent increase in the number of GLUT 4 transporters incorpotated into the muscle membrane

Question 108

How does exercise affect insulin sensitivity?

Answer 108

Exercise also increases the insulin sensitivity of muscle, and causes an insulin-independent increase in the number of GLUT-4 transporters incorporated into the muscle membrane

Question 109

How long do the effects of exercise on BG last?

Answer 109

This effect persists for several hours after exercise and regular exercise can produce prolonged increases in insulin sensitivity

Question 110

In non-active muscle, ______ binds to its receptor, which then leads to glucose transporters, GLUT_, migrating to the cell membrane, allowing _______ to enter

Answer 110

In non-active muscle, insulin binds to its receptor, which then leads to glucose transporters, GLUT4, migrating to the cell membrane, allowing glucose to enter

Question 111

In active muscle, GLUT4 transporters can migrate to the membrane without ______ being present, so exercise causes glucose uptake __________ of _______

It also increases the _________ of the muscle to insulin

Answer 111

In active muscle, GLUT4 transporters can migrate to the membrane without insulin being present, so exercise causes glucose uptake independently of insulin

It also increases the sensitivity of the muscle to insulin

Question 112

How does the body get energy during starvation?

Answer 112

When nutrients are scarce, body relies on stores for energy – when adipose tissue is broken down fatty acids are released

FFA’s can be readily used by most tissues to produce energy and liver will convert excess to ketone bodies which provides an additional source for muscle and brain!

Question 113

after a period of starvation, what the does the brain use for energy?

Answer 113

After a period of starvation, the brain adapts to be able to use ketones

Question 114

Why is adipose tissue broken down first in starvation and what is the last store in starvation to be deplted?

Answer 114

This serves to “spare protein” which would otherwise be broken down excessively to provide gluconeogenic substrates. (Loss of protein -very weakening, vulnerable to infection). Last store to be depleted in starvation.

Works well as long as there is a functioning pancreas secreting insulin as ketone body uptake is insulin dependent

In diabetes, lif threatening ketoacidosis may result (see later)

Question 115

what does ketone bodies need for uptake?

Answer 115

ketone body uptake is insulin dependent

Question 116

is starvation in a diabetic person more life threatening?

Answer 116

In diabetes, life threatening ketoacidosis may result (see later) as ketone bodies uptake is insulin dependant

Question 117

what is diabetes mellitus?

Answer 117

Loss of control of blood glucose levels

diabetes = flow, mellitus = sweet

patients produce large volumes of sweet tasting urine

Occurs in two forms: Type I and Type II

Question 118

what is the cause of type 1 diabetes?

Answer 118

Autoimmune destruction of the pancreatic b-cells destroys ability to produce insulin and seriously compromises patients ability to absorb glucose from the plasma

10% of diabetic patients are insulin-dependent

Question 119

What does untreated type 1 diabetes cause?

Answer 119

Untreated type 1 diabetes leads to many complex changes in the body which ultimately cause starvation and death.

Before the discovery of insulin, survival, post-diagnosis, was between 2 weeks and 18 months

Question 120

What is the management of type 1 diabetes and what happens if this doesnt happen?

Answer 120

Current day – patients need daily insulin injections, (peptide hormones cannot be given orally)

Type I patients have an absolute need for insulin, without it they become excessively wasted, develop ketoacidosis, coma and die

“Starvation in the midst of plenty”

Question 121

Summary diagram:

homeostatic control of blood glucose and then in diabetes

Answer 121

Body thinks it doesn’t have any glucose so starts making more and again still cant be taken up and you are then in a viscous cycle

Question 122

How has sirvival time changed before and after the discovery of insulin?

Answer 122

Pre-insulin’s discovery, survival post-diagnosis was between 2 weeks and 18 months. After insulin, >75 years, >300 million lives saved by insulin

JJR Macleod, Aberdeen medical graduate and later Physiology Professor won Nobel Prize in 1923 for discovery of insulin with Canadian colleagues

Question 123

what happens when nutrients are scare?

Answer 123

When nutrients are scarce, body relies on stores for energy – when adipose tissue is broken down fatty acids are released. FFA’s can be readily used by most tissues to produce energy and liver will convert excess to ketone bodies which provides an additional source for muscle and brain!

Question 124

What happens to ketone boddies in insulin dependant diabetes?

Answer 124

in poorly controlled insulin-dependent diabetes a lack of insulin depresses ketone body uptake

They build up rapidly in the plasma and because they are acidic create life threatening acidosis (ketoacidosis or ketosis) with plasma pH < 7.1

Death will occur within hours if untreated

Question 125

how are ketones detected?

Answer 125

Ketones detectable in urine and produce distinctive acetone smell to breath

Question 126

what is type 2 diabetes?

Answer 126

Type II Diabetes – Non-Insulin Dependent Diabetes Mellitus (NIDDM)

Peripheral tissues become insensitive to insulin = insulin resistance. Muscle and fat no longer respond to normal levels of insulin. This is either due to an abnormal response of insulin receptors in these tissues or a reduction in their number

b-cells remain intact and appear normal, there may even be hyperinsulinaemia

90% of diabetic patients are insulin-resistant (NIDDM)

insulin not causing a response so make some more

Question 127

What features of a person are typically associated with type 2 diabetes?

Answer 127

Typically associated with obesity

Usually appears >40yrs but age decreasing

High sugar and animal fat diet together with little exercise are major contributors

Question 128

[BG] elevated in both Type I and Type II Diabetes for different reasons:

Type I = inadequate insulin release = increased ­[BG]

Type II = inadequate tissue response = increased ­[BG]

Hyperglycaemia (elevated [BG]) is the diagnostic criterion for diabetes.

How is it detected?

Answer 128

Detected by performing a “Glucose Tolerance Test”

Patient ingests glucose load after fasting [BG] measured. [BG] will normally return to fasting levels within an hour, elevation after 2 hours is indicative of diabetes. Does not distinguish Type I from II.

Question 129

What is a concern that can result form poorly controlled diabetes?

Answer 129

Hyperglycaemia

Question 130

The reason for concern about hyperglycaemia in both type I and type II patients is that glucose is a highly reactive molecule which can eventually produce long-term problems that may be very serious = diabetic complications: what are they?

Answer 130

Retinopathy

Neuropathy

Nephropathy

Cardiovascular Disease