MET EOYS3 Flashcards
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
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
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 causes weight gain? [2]
- Sulfonylureas - e.g. gliclazide, glibenclamide and tolbutamide
- Metformin
- SGLT2 Inhibitors
- Thiazolidinediones e.g Pioglitazone or Rosiglitazone
Which of the following drug treatments for diabetes causes weight gain? [2]
- Sulfonylureas - e.g. gliclazide, glibenclamide and tolbutamide
- Metformin
- SGLT2 Inhibitors
- Thiazolidinediones e.g Pioglitazone or Rosiglitazone
Under normal B12 and Folate levels what is homocysteine converted to? [1]
Deficient B12 and Folate levels what is homocysteine converted to? [1]
What pathology does this lead to? [1]
When the body has Folate and vit B12 (necessary co factors for)
* methionine synthase enzyme: converts homocysteine –> methionine.
BUT: without Folate and B12:
* homocysteine -> homocysteine thiolactone (damages endothelium
= ATHEROSCLEROSIS
Chronic deficiency in folate causes low [] and high blood [] levels
Chronic deficiency in folate causes low methionine and high blood homocysteine levels
When chronic folate deficiency: homocysteine is converted to toxic [] which damages endothelium.
When chronic folate deficiency: homocysteine is converted to toxic thiolactone which damages endothelium.
What is metabolic syndrome a combination of? [4]
Syndrome of increased CVD risk because of:
- Insulin resistance/ Type II diabetes
- Abdominal obesity
- Dyslipidaemia (particularly hypertriglyceridaemia)
- Hypertension
These factors cluster together more frequently than expected by chance !
Role of the following of on firing of ECC vesicles?
5HT [1]
Leptin [1]
Ghrelin [1]
5HT - increases firing
Leptin - decreases firing
Ghrelin - decreases firing
Which cells release PYY? [1]
Where is PYY predominately found? [1]
What effect does PYY have on NPY [1] and POMC neurones [1]
Which cells release PYY? [1]: L cells in GI tract
Where is PYY predominately found: Colon –> rectum
What effect does PYY have on NPY: inhibits
and POMC neurones: activates
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
Role of malonyl-coA? [1]
[] malonyl-coA supresses food intake
[] malonyl coA increases food intake
Malonyl-CoA is the substrate for fatty acid synthase, but it is a key determinant for the entry of fatty acids into the mitochondria, and appears to play a pivotal signaling role in appetite regulation.
Increased malonyl-coA supresses food intake
Decreased malonyl coA increases food intake