BIOC L11 - diabetes, dysregulation of glucose, and fat metabolism

What fasting glucose measurement is indicative of diabetes?

>7.0mmol/L

What random glucose measurement is indicative of diabetes?

>11.1mmol/L

What HbA1c measurement is indicative of diabetes?

>50mmol/mol

In what type of diabetes is ketoacidosis mroe common and why?

Type.1 because there is no insulin, only fats can be broken down for energy and insulin cannot inhibit ketogenesis

What are self-diagnosable symptoms of diabetes?

thirst, frequent urination, fatigue, blurred vision, coma

What are other symptoms of diabetes that need to be tested?

glycosuria, osmotic diuresis and dehydration

How does T2D develop?

associated with metabolic stress and inflammation and obesity eventually leading to insulin resistance

What happens in the early stages of insulin resistance in a pre-diabetic?

insulin output increased to have same effect of glucose uptake, cells become unable to cope with higher levels of glucose and limits ability of insulin to cause uptake

What happens with insulin resistance in a diabetic?

fasting glucose remains elevated bteween meals

At what glucose concentration in the blood can kidneys no longer rcvoer glucose from ultrafiltrate?

At 12-15mmol/L in blood, glucose starts to be seen in urine.

What are the process that are usually stimulated by insulin that become less responsive in a diabetic?

Glucose uptake, glycolysis, and fatty acid uptake

What are the processes that are usually inhibited by insulin which remain active in diabetics?

Gluconeogenesis, lipolysis, fatty acid oxidation, and ketogenesis

Why do chylomicrons accumulate in the blood in T2D?

chylomicrons transport fat however insulin isn't stimulating fattya cid uptake so chylomicrons remain in circulation

Why does the liver increase production of glucose in T2D?

lipolysis isn't inhibited by insulin so fatty acids are released into the blood and go to the liver, where the breakdown creates ATP to fuel gluconeogenesis

Why does the liver increase production of TAGs and VLDLs in T2D?

fatty acids are used in TAG synthesis which circulate on VLDLs around the body

Why do VLDLs remain in circulation in T2D?

insulin is not stimulating LPL to break down TAGs in VLDL

How does loss of insulin function increase ketone production?

glucagon promotes shuttling of FA into mitochondria for breakdown

What are 2 theories about how insulin resistance occurs?

oxidative stress and inflammation

What is oxidative stress?

mitochondria are working hard, under stress. highly oxidising molecules sch as hydrogen peroxide a byproduct of mitochondira function and are toxic to the cell

What does oxidative stress lead to?

processes which inhibit insulin signaling

How does inflammation affect insulin resistance?

various cytokines interact with receptors and stimulate activity that inhibits components of the insulin signaling path

How does fatty liver develop?

circulating glucose is made into TAGs which cannot be stored in adopose and must be stored in the liver causing appearance of lipid rich droplets leading to inflammation and cirrhosis

What is cirrhosis?

liver damage

What is the effect of insulin resistance in adipose tissue?

insulin cannot inhibit hormone sensitive lipase so TAGs in adipose are broken down in FAs and release into blood towards liver so increased production of VLDLs

What are lifestyle treatments for T2D?

diet intervention and physical exercise

What are drugs for the treatment of T2D?

metformins which increase insulin sensitivity in tissues and GLP-1 agonists increase insulin secretion and help to lose weight

What is a specific action of metformins?

increases signaling molecule AMP kinase making insulin response more stimulated