LECTURE 23 - diabetes Flashcards
1
Q
What is diabetes?
A
- disease of dysregulated glucose control
- a disease of high glucose (and BP and lipids)
- caused by insufficient Acton of the hormone insulin
- common
- associated with significant morbidity
- expensive to treat
- part of the metabolic syndrome
2
Q
How is diabetes classified?
A
- Type 1 (single gene mutations of endocrine pancreas or function of endocrine pancreas, defects of mitochondria )
- Type 2 (you can generate glucose intolerance during pregnancy - tends to go away after pregnancy but is usually a signal for getting type2 later in life)
- monogenic diabetes - maturity-onset diabetes of the young (MODY), mitochondrial diabetes, neonatal diabetes
- other - gestational diabetes, drug-induced, endrocrinopathies, secondary diabetes
3
Q
What is type 1 diabetes?
A
- insulin dependent diabetes, juvenile-onset
- 0.3% of British population
- dramatic onset
- production of ketones
- not enough insulin to bring glucose into cells to use as energy so breaks down fat instead as an energy source
- the liver converts fatty acids into ketones and these ketones are released into the blood stream to be used as energy
- these ketones are very acidic - can lead to ketoacidosis
Cause: insulitis (disease of pancreases caused by infiltration of lymphocytes), autoimmune destruction of pancreatic beta cells
4
Q
What is type 2 diabetes?
A
- non insulin dependent, maturity-onset
- insulin resistance
- relative insulin deficiency
- 8% of British pop.
- no ketones
- associated with obesity
- metabolic syndrome consists of 2 things: type 2 diabetes and cardiovascular disease
- increased in adipose tissue and the associated problems - adipocyte malfunction, insulin resistance
5
Q
What is metabolic syndrome?
A
- has 2 components: type 2 diabetes and cardiovascular disease
- caused by genetics, changes in diet, inactivity and obesity
6
Q
What do the components of metabolic syndrome alter?
A
- altered energy homeostasis
- AMP activated protein kinase involved in regulation of energy homeostasis
- it phosphorylates and alters function of proteins
- regulated by AMP levels, malfunction affects energy homeostasis. affected by excessive so this stimulates AMP kinase
- metformin acts on AMP activated kinase to lower blood sugar
7
Q
What are the symptoms of diabetes?
A
- weight loss
- extreme fatigue
- prone to infections
- osmotic symptoms (polyuria, thirst, blurred vision)
- slow healing wounds
- tingling pain or numbness in the hands/feet
8
Q
How is diabetes diagnosed?
A
- measure urine glucose
- measure blood glucose
- random: blood taken as they are with finger prick. >11.1mM
- fasting: asked to fast.>7.0mM
- oral glucose tolerance test
- asked to fast, blood taken, given a high sugar drink and then wait 2 hours to and measure blood glucose over 2 hours to see how fast glucose removed from body, speed at which glucose is cleared gives indication of diabetes
- HbA1c test: measures blood glucose over past 2-3 months, used instead of fasting sugar measurements (haemoglobin becomes glycated if there’s lots of glucose in blood stream
Increase in presence of glycated haemoglobin the higher the fasting sugar )
9
Q
What is the pathology that causes diabetes?
A
- insulin resistance
- insulin deficiency
10
Q
What does insulin do to carbohydrate metabolism?
A
- ↑ rate of glucose transport across the cell membrane in muscle and adipose tissue
- ↑ the rate of glycolysis in muscle and adipose tissue
- stimulates the rare of glycogen synthesis in adipose, muscle & liver
- ↓ the rate of glycogen breakdown in muscle and liver
- inhibits the rate of glycogenolysis and gluconeogenesis in the liver
- ↑ the rate of glucose oxidation in the liver and adipose
–> overall effect of insulin is to ↓ breakdown of stored fuel and build with what is around
11
Q
What does insulin do to fat metabolism?
A
- inhibits rate of lipolysis in adipose
- stimulates fatty acid and triacglycerol synthesis sin adipose and liver
- ↑ VLDL formation in liver
- ↑ lipoprotein lipase activity in adipose tissue; ↑ uptake of triglycerides from blood
- ↓ rate of fatty acid oxidation in liver
- ↑ rate of cholesterolgenesis in liver
–> overall effect is to inhibit lipolysis and therefore decrease release of fatty acids
12
Q
Where is insulin made?
A
Beta cells of Islets of Langerhans
13
Q
How is insulin released?
A
- released in response to elevated [glucose]
- glucose enters by GLUT2 and is metabolised and phosphorylated –> ↑ ATP production
- ATP binds to K+ATP channel and plasma membrane
- binding –> closure of K+ATP –> membrane depolarisation and opening of L type Ca+ channels
- influx of Ca2+ = mobilisation of insulin containing vesicles –> exocytosis of insulin which causes cascade of events e.g. PI3 kinase -
activation of insulin gene expression - Ca increases in the cell when glucose increases in the cell
- Ca can be measured to measure the activity of beta cells
14
Q
What happens to cell calcium in response to glucose?
A
- can track [Ca2+] in beta cells from low (0.5mM) to high (11mM) of glucose
- at low, some small oscillations, some small peaks
- dramatically increased in response to glucose, this leads to release of insulin
- mechanisms that lead to change in calcium are important to know to enable targeting with drugs
- cell calcium spikes when cells is presented with high glucose - stays high until glucose is washed away
- circadian control of insulin, more able to release it during the day than at night
15
Q
How can we treat Type 1 diabetes?
A
- lifestyle (eat healthily and regularly)
- insulin injections (due to lack of insulin). Capillary blood glucose testing and insulin administration, glucometer measure blood glucose to tell you how much insulin to inject
