Lecture 27, 28 - Glucose metabolism and diabetes Flashcards
*Insulin release and actions of insulin
- main regulators of glucose
- what inhibits insulin
Acitons on liver, muscle and fat
Release
- Basal secretion is pulsatile
- in pancrease glucose enters beta cells, atp is produced by glycolysis, this clsoes K channels and leads to calcium influx and insulin release
- Glucose is main regulator, when this increases insulin released (also GLP-1 and somatostatin decreases)
what inhibits insulin - low glucose, somatostatin
Action
- Liver - inhibits glyogenolysis and gluconeogensis
- Muscle - increases glucose transport and glycolysis, amino acid uptake and protein synthesis
- Adipose tissue - same as muscle (increase fat storage and decrease fat breakdown)
Ketones
*-diabeteic ketoacidosis
ketogenesis - oxidation of free fatty acids - form ketone bodies
-this is so body (muscle adn liver) can use ffa for energy when low glucose (cannot be used by brain or red blood cells)
Diabetic ketoacidosis - due to no insulin, get starvation so ketone bodies made then get uncontrolled glycogenolysis and protein hydrolysis and ends up in GLUT 4 inactive and get hyperglycaemia –> diabeteic ketoacidosis
can get cognitive dysfunction, sweating, coma
*Hypoglycaemia causes
how body stops this
- insulin in patients with diabetes (normally this is switched off)
- glycogen is stimulated
pancreas secretes glucagon, also adrenaline and cortisol released, GH and ACTH are relased
What % of energy is stored as carbs, fat and protein
- what is fasting glucose cut off to suggest diabetes?
- what is HbA1c?
Fat - 70-80%
Protein - 20%
Carb 1-2%
glucose > 7mol/L
HbA1c - >50 mmol/mol
What is metabolic syndrome?
Central obesity + 2 out of
- hypertension
- abnormal glucose
- high triglycerides
- low HDL
-these people will have insulin resistance
- may have acanthosis nigricans
- PCOS - people with pcos are normally always insulin resistant
-causes insulin resistance to muscle, liver and fat
Insulin resistance can lead to features of metabolic syndrome due to hyperinsulinemia causing retention of salt and water in kidney
What causes insulin resistance?
- Genetics
- Environment - intrauterine, obesity
- increase visceral fat and therefore stored triglyceride - large adipocytes are resistant to insulin so do not suppresses lipolysis
- increase lipolysis leads to increase release of NEFA and glycerol
- these and inflammatory cytokines aggravate insulin resistance in muscle and liver
Consequences of insulin resistance
- can cause increased hepatic glucose output and triglyceride synthesis (-can cause fatty liver)
- uptake of glucose in muslce cells reduce
- hyperinsulinaemia only way to maintain glucose levels
- GLucose levels increasing can cause beta call toxicty , and also lipotoxicity to beta cells from so much fat breakdown
- beta cells start to fail - now have post prandial hyperglycaemia
-Beta cell wil reduce function - can result in no insulin secretion
What are causes of Truncal obesity and what can this lead to?
-Foetal programing, exces energy intake, low PA, genetic predospotion
Can lead to - glucose intolerance - type 2 diabetes
- hypertension
- dyslipidaemia
- endothelial dysfunction
Consequences of diabetes
microvascular
- retinopathy– damage to blood vessles in eyes, can lead to blindnes
- nephropathy - buring, numbmess, ulcers and foot infections
- nephropathy - proteinuria - common cause of ESRF
Types of insulin
Humalog - short acting
Lantus - long acting
Macro vascular complicaitons
- IHD - higher rates of heart attack
- Peripheral vascular disease - further complicates neuropathy
Type 1 vs type 2 diabetes and management
Type 2 - obese, metabolic syndrome features, family history, older, dont need insulin till 5-10 years
Type 1 - autoimmune beta cell destruction, abrupt symptoms, younger, no family history, ketosis prone, require insulin from diagnosis and to sustain life
Management - lifestyle factors of diet and exercise, medication to control glucose
- metformin
- attend to BP, lipids, smoking ect.
