MET EOYS6 Flashcards
State the roles of:
NPY / AgRP neurones [1]
POMC / CART neurones [1]
NPY / AgRP neurones: signals hunger and stimulates food intake
POMC / CART neurones: signals satiety and reduces food intake
Which of the following is a type of diabetes where antibodies produced
Latent Autoimmune Diabetes of Adults
Type two diabetes
Gestatational diabetes
Maturity Onset Diabetes of the Young
Which of the following are antibodies produced
Latent Autoimmune Diabetes of Adults type 1.5
Type two diabetes
Gestatational diabetes
Maturity Onset Diabetes of the Young
Which of the following type of diabetes is usually caused by one gene
Latent Autoimmune Diabetes of Adults
Type two diabetes
Gestatational diabetes
Maturity Onset Diabetes of the Young
Which of the following type of diabetes is usually caused by one gene
Latent Autoimmune Diabetes of Adults
Type two diabetes
Gestatational diabetes
Maturity Onset Diabetes of the Young
PYY has the biggest effect on which part of the GI system
Stomach
Duodenum
Jejunum
Ileum
Colon
PYY has the biggest effect on which part of the GI system
Stomach
Duodenum
Jejunum
Ileum
Colon
PYY has the is produced from which type of cells:
D cells
A cells
L cells
B cells
PYY has the is produced from which type of cells:
D cells
A cells
L cells
B cells
Thiolactone is produced due to a deficiency in which two molecules [2]
What does increased thiolactone levels lead to? [1]
B12 & Folate Deficiency
Leads to atherosclerosis
A patient with which of the following HbA1c reading would have diabetes
41 mmol/mol
43 mmol/mol
45 mmol/mol
47 mmol/mol
49 mmol/mol
A patient with which of the following HbA1c reading would have diabetes
41 mmol/mol
43 mmol/mol
45 mmol/mol
47 mmol/mol
49 mmol/mol - 48 is the cut off
How does obesity cause extrinsic insulin resistance? [3]
How does obesity cause intrinsic insulin resistance? [3]
What is net effect of obesity and insulin? [1]
Which aspects of obesity causes extrinsic insulin resistance? [3]
* Accumulation of lipids and FFA
* Chronic inflammation
* Altererd adipokiine (cytolines from FA)
How does obesity cause intrinsic insulin resistance? [3]
* Mitochondrial dysfunction
* Ox stress
* ER stress
Overall: causes hyperinsulinaemia, whcih increases lipid synthesis and insulin resistance
Whats difference between insulin resistance and DMT2?
Insulin resistance: adapt by : become bigger, increase in number and produce more insulin (compensatory hyperinsulinaemia)
DMT2: resistance AND failure
How does islet compensation occur if there is impaired function from obesity of B-cells?
As the impacts of obesity occur the susceptible cells will decrease in number/function –> B-cell apoptosis
Impaired genetic compensation: genetic component
How do most of the genes associated with DMT2 influence insulin [2]
impairing insulin secretion rather than insulin action
Gene risk variants are to do with the regulators of β cell turnover or regeneration
Impaired genetic comepensation: environmental component
Which envrionmental factors within body influence DMT2 infuence? [4]
Increased circulating FFAs (lipotoxicity)
Hyperglycaemia (glucotoxicity)
Combination of the two (glucolipotoxicity)
Hyperinsulinemia
What is Monogenic diabetes? [1]
Specifically how is it caused / insulin affected? [2]
Caused by a mutation in a single gene (one of over 40 genes): Means theres 40 types of MODY
Most cases are Maturity Onset Diabetes of the Young (MODY)
Caused by:
* prevent the insulin sensing glucose metabolism in B-cells
- Due to: impairment of insulin secretion/pancreatic βcell dysfunction
What is LADA?
What are characteristics of LADA? [2]
Latent Autoimmune Diabetes of Adults (LADA): Features of both Type 1 and Type 2 (type 1.5)
Immunologically similar to T1 - produce DMT1 antibodies but destruction is slower than in T1.
What HbA1c is used as cut off for diabetes? [1]
An HbA1c of 48 mmol/mol (6.5%) is recommended as the cut point for diagnosing diabetes
MoA of Metformin [3]
Inhibits gluconeogenesis in the liver
Inhibits CAMP + PKA pathway.
Also increases glucose transport - increasing uptake at skeletal muscle. Opposes insulin resistance through various mechanisms.
From Drugs List:
acts by activation of the AMP-activated protein kinase (AMPK)
increases insulin sensitivity
decreases hepatic gluconeogenesis
Which treatments for DMT2
inhibitGNG [1]
increase insulin sensistivity [2]
stimulate insulin secretion [2]
two others? [2] ?
Inhibits GNG:
* Metformin: inhibits GNG at liver
Increases insulin sensitivity:
* Metformin
* Thiazolidinediones: Enhance GLUT4 uptake into the cell membranes (in adipocytes - so causes weight gain) via PPAR-y gene
Stimulation of insulin secretion:
* Sulfonylureas: close ATP sensitive K chance which regulates insulin secretion
* Prandial glucose regulators: same as above but faster
Others:
* GL1-P receptor agonists
* DPP-4 inhibitors: DPP-4 inhibits GL1-P
How does DKA occur?
In the absence of insulin there is an unrestrained increase in hepatic gluconeogenesis and peripheral glucose uptake by tissues such as muscle is reduced
High circulating glucose levels result in an osmotic diuresis (since increased glucose in urine which pull more water into urine) by the kidneys and consequent dehydration and loss of electrolytes
Peripheral lipolysis occurs leading to an increase in circulating free fatty acids (FFAs) which are then broken down to acetyl-coenzyme A (CoA), but little oxaloacetate within the liver cells and this, in turn, is converted to ketone bodies within the mitochondria. (no Kreb’s cycle)
Ketone bodies are in excess
Ketone bodies dissociate: H+
Causes metabolic acidosis w/ raised anion gap.
Vomiting leads to further electrolye loss
What is difference between non-proliferative and proliferative retinopathy?
Both occur because of damage to BV in back of eye
Non-profilerative: ‘Cotton wool’ dilation of retina veins causes internal haem. oedema causes vision loss
Proliferative: New BV proliferate near optic disc and bleed: detachment of retina
MoA of diabetic nephropathy?
PKA activation -> collagen/fibronectin proliferation -> capillary occlusion -> thickening of glomerular basement membrane. PKA activation -> increase in NADPH -> ROS
MoA of diabetic retinopathy?
Hyperglycaemia -> increased PKA activity -> reduced retinal blood flow due to vasoconstriction
PKA activity -> vascular permeability angiogenesis -> macular oedema
Which of the following drug treatments for diabetes utilise the followng mechanism of actions?
Inhibits liver gluconeogenesis and enhances insulin sensitivity
- Sulfonylureas - e.g. gliclazide, glibenclamide and tolbutamide
- Metformin
- SGLT2 Inhibitors
- Thiazolidinediones e.g Pioglitazone or Rosiglitazone
Which of the following drug treatments for diabetes utilise the followng mechanism of actions?
Inhibits liver gluconeogenesis and enahnaces insulin sensitivity
- Sulfonylureas - e.g. gliclazide, glibenclamide and tolbutamide
- Metformin
- SGLT2 Inhibitors
- Thiazolidinediones e.g Pioglitazone or Rosiglitazone
Which of the following drug treatments for diabetes utilise the followng mechanism of actions?
- Sulfonylureas - e.g. gliclazide, glibenclamide and tolbutamide
- Metformin
- SGLT2 Inhibitors
- Thiazolidinediones e.g Pioglitazone or Rosiglitazone
Which of the following drug treatments for diabetes utilise the followng mechanism of actions?
- Sulfonylureas - e.g. gliclazide, glibenclamide and tolbutamide
- Metformin
- SGLT2 Inhibitors
- Thiazolidinediones e.g Pioglitazone or Rosiglitazone
Bind and close K+ channel in beta cells to
depolarise the cell and release insulin
Which cels in the GI tract sense the luminal envrionment? [1]
Describe how their structure is adapted to their role
Enteroendocrine Cells:
Apex: Long processes into lumen + microvilli: for sampling the luminal nutrient environment.
Basal side: stores many vesicles, containing appetite regulating hormones. close to nerve endings - hormones bind to nerve receptors to signal orexigenic or anorexigenic pathways
AGRP/NPY neurones in arcuate nucleus of hypothalamus are activated by which hormone? [1]
What biochem effect does this have? [1]
AGRP/NPY neurones in arcuate nucleus of hypothalamus are activated by which hormone? [1]
Ghrelin
What biochem effect does this have? [1]
Causes a release of Y1 receptors
Label A-E xx
A: GLP-1
B: PYY
C: Ghrelin
D: Leptin
E: Insulin
Explain how overall food intake decreases in response to increased energy levels? [1]
Explain how ^ occurs [3]
Increased M-CoA - stimulates FA synthesis –» therefore suppresses appetite
More ATP over AMP -> increased denovo FA synthesis -> increased M-CoA -> stimulation of POMC/CART + suppression NYP/AgRP -> decreased food intake
Label the types of diabetic retinopathy [2]
A: Non-proliferative - cotton wool spots
B proliferative
What type of diabetic retinopathy is depicted? [1]
Nonproliferative
Funduscopic features of nonproliferative diabetic retinopathy include retinal hemorrhages and hard exudates (yellow patches)
What type of diabetic retinopathy is depicted? [1]
Proliferative
The key funduscopic feature of proliferative diabetic retinopathy is neovascularization, seen here around the optic disk.
Which of the following is most associated with this skin condition?
Polycystic ovarian syndrome
Graves’ disease
Small cell lung cancer
Addison’s disease
Methotrexate use
Which of the following is most associated with this skin condition?
Polycystic ovarian syndrome
Graves’ disease
Small cell lung cancer
Addison’s disease
Methotrexate use
This is a typical appearance of acanthosis nigricans; symmetrical, dark, ‘velvety’ plaques which arise on the neck, axillae and groin creases in conditions associated with raised insulin, such as:
Obesity
Type 2 diabetes
Polycystic ovarian syndrome
Cushing’s disease
