Diabetes

Question 1

What % of DM diagnoses are type 2?

Answer 1

85%

Question 2

Name 3 places the body can get glucose from

Answer 2

Diet

Breakdown of glycogen stores (glycogenolysis)

Formation of glucose (gluconeogenesis)

Question 3

Is glucose hydrophilic or hydrophobic?

What does this mean about transport into cells?

Answer 3

Hydrophilic

Diffuses slowly across lipid cell membrane
Requires specific transport proteins to move into cells

Question 4

List some differences between GLUT and SGLT transporters

Answer 4

GLUT -
Facilitated diffusion
Not energy dependent

SGLT -
Use sodium to move glucose against concentration gradient

Question 5

Where are the two types of SGLT transporters found?

Answer 5

SGLT-1
Intestines

SGLT-2
Kidneys

Question 6

Which GLUT transporter is insulin dependent?

Where is it mainly found?

Answer 6

GLUT-4

Fat and muscle

Question 7

Describe gluconeogenesis

Answer 7

Production of glucose from molecules that aren’t carbohydrates.

Substrates:

Lactate (non-oxidative metabolism, Kreb’s cycle)

Glycerol (fats)

Glutamine and alanine (protein)

Occurs in liver and kidneys

Question 8

Describe glycogen and glycogenolysis

Answer 8

Multi branched polysaccharide of glucose, storage molecule of glucose

Stored in liver and muscle cells

Question 9

Describe insulin

Answer 9

51 amino acids peptide hormone

2 protein chains (alpha and beta) linked by disulphide bonds

Question 10

Where is insulin produced?

Answer 10

B-cells of Islets of Langerhans in the pancreas

Question 11

Where is glucagon produced?

Answer 11

a-cells of Islets of Langerhans in the pancreas

Question 12

Where is somatostatin produced?

What is its role?

Answer 12

gamma-cells

Strong inhibitor of insulin and glucagon

Question 13

Describe biphasic insulin secretion

Answer 13

First phase - rapid onset, lasts 10 minutes

Second phase - prolonged plateau lasting as long as hyperglycaemia persists

Question 14

Why is it presumed insulin levels are regulated by release rather than synthesis?

Answer 14

Only a portion of stored insulin is released even under maximal stimulation

Question 15

Name 6 major actions of insulin

Answer 15

Release of GLUT-4 from storage vesicles to cell walls

Inhibit gluconeogenesis

Glycogen synthesis

Promotes protein synthesis

Promotes lipogenesis

Suppress ketogenesis

Question 16

What can increase the levels of glucagon?

Answer 16

Fasting

Exercise

Stresses e.g. trauma, infection

Question 17

List 5 major actions of glucagon

Answer 17

Stimulates gluconeogenesis

Stimulates glycogenolysis

Promotes proteolysis

Stimulates lipolysis

Promotes ketogenesis

Question 18

What do L-cells of the small intestine produce?

Answer 18

Glucagon-like peptides (GLP)

Gastric inhibitory peptide (GIP)

Question 19

Where is GLP and GIP made?

Answer 19

L cells of the small intestine

Question 20

What stimulates the release of GLP and GIP?

Answer 20

Oral glucose loading

IV glucose has less of a response

Question 21

How does adrenaline affect insulin and glucagon release?

Answer 21

Adrenaline inhibits insulin and promotes glucagon secretion

Question 22

How does the autonomic nervous system affect insulin and glucagon release?

Answer 22

Sympathetic neurons - release noradrenaline - stimulates glucagon + inhibits insulin

Parasympathetic neurons - stimulate insulin, inhibit glucagon

Question 23

How is cortisol related to insulin?

Answer 23

Cortisol directly inhibits insulin secretion

Question 24

Cortisol and growth hormone promote _____ and inhibit ______

Answer 24

Promote gluconeogenesis

Inhibit glucose transport

Question 25

Define diabetes mellitus

Answer 25

A heterogeneous complex metabolic disorder characterised by elevated blood glucose concentration secondary to either resistance to the action of insulin, insufficient insulin secretion, or both

Question 26

What are the four classifications on the WHO spectrum of disorders of glucose metabolism

Answer 26

Normal Impaired fasting glycaemia Impaired glucose tolerance Diabetes

Question 27

How is type 1 diabetes classified?`

Answer 27

Autoimmune disease with selective destruction of β-cells resulting in complete insulin deficiency Can only be treated with insulin

Question 28

Who normally suffers from type 1 diabetes?

Answer 28

Younger, leaner patients 5-10% of all diabetes cases Can be associated with other immune diseases e.g. thyroid disorders, coeliac disease

Question 29

Name four symptoms of type 1 diabetes

Answer 29

Polyuria Polydipsia Weight loss Hyperglycaemia

Question 30

Why do diabetics have polyuria?

Answer 30

Hyperglycaemia results in glycosuria - exceeds renal capacity to reabsorb Glucose in urine inhibits concentrating ability of kidney Water is moved down a concentration gradient with glucose resulting in polyuria

Question 31

Why do diabetics have polydipsia

Answer 31

Polyuria due to hyperglycaemia, water needs replacing to maintain fluid balance Hyperglycaemia also directly stimulates thirst response

Question 32

Why do diabetics experience weight loss?

Answer 32

Unopposed lipolysis and proteolysis (no insulin to appose these systems) The results of these form gluconeogenesis precursors

Question 33

What is diabetic ketoacidosis?

Answer 33

When high levels of ketones are produced as an alternative energy source due to lack of glucose absorption into cells due to lack/insensitivity to insulin

Question 34

Give 3 symptoms of DKA

Answer 34

Shock (dehydration) High respiratory rate Abdominal pain

Question 35

Define type 2 diabetes mellitus

Answer 35

Heterogeneous condition Characterised by insulin resistance and hyperinsulinemia Loss of first phase of insulin response B-cell exhaustion can occur

Question 36

What other symptoms are usually present with T2DM?

Answer 36

Central/visceral obesity Dyslipidaemia Cardiac factors (HTN)

Question 37

How does Metformin work?

Answer 37

Decreases hepatic gluconeogenesis

Question 38

What is first line treatment for T2DM?

Answer 38

Diet, exercise and lifestyle measures

Question 39

List the three broad categories of complications from diabetes

Answer 39

Hypoglycaemia Microvascular Macrovascular

Question 40

Name 3 microvascular complications of diabetes

Answer 40

Nephropathy Retinopathy Neuropathy

Question 41

Name 3 macrovascular complications of diabetes

Answer 41

IHD Cerebrovascular disease (CVD) Peripheral vascular disease

Question 42

Which type of glucose transporter is found on B-islet cells?

Answer 42

GLUT 2

Question 43

Where are SGLT1 and SGLT2 transporters found?

Answer 43

SGLT1 - intestines (absorption from food) SGLT2 - kidneys (reabsorption) 1 intestine, 2 kidneys

Question 44

What is lipolysis?

Answer 44

The breakdown of fats and other lipids by hydrolysis to release fatty acids

Question 45

What affect does insulin have on glucose production, glucose utilisation, and lipolysis?

Answer 45

Glucose production - DECREASES Glucose utilisation - INCREASES Lipolysis - DECREASES

Question 46

What affect does glucagon have on glucose production, glucose utilisation, and lipolysis?

Answer 46

Glucose production - INCREASES Glucose utilisation - DECREASES Lipolysis - INCREASES

Question 47

List/draw the 6 steps to insulin secretion in response to glucose in B-cells in the pancreas

Answer 47

Glucose moves into B-cell via GLUT-2 Glucose is metabolised which increases ATP ATP-dependent K+ channels close This leads to membrane depolarisation This leads to opening of voltage gated Ca2+ channels and influx this leads to exocytosis of stored insulin vesicles

Question 48

Why does insulin have different affects on different target cells?

Answer 48

Insulin activates an insulin receptor but then different secondary pathways can be activated

Question 49

Describe the relationship between insulin and GLUT 4

Answer 49

GLUT 4 is stored in intracellular vesicles Insulin promotes fusion of vesicles and transporter insertion into cell walls This facilitates glucose transport into cells

Question 50

Which enzyme does insulin promote activation of?

Answer 50

Glycogen synthase | - makes glycogen from glucose

Question 51

What is glucagon secretion regulated by?

Answer 51

Blood glucose levels Hypoglycaemia increases glucagon secretion Hyperglycaemia inhibits glucagon secretion

Question 52

Is the post-absorptive state of glucose catabolic or anabolic?

Answer 52

Post-absorptive state is catabolic

Question 53

Is the post-prandial (fed) state of glucose catabolic or anabolic?

Answer 53

Post-prandial is anabolic