Diabetes Flashcards
What are the functions of the pancreas?
Pancreas has two functions. Exocrine function forms the bulk of the gland (Alkaline secretions through pancreatic duct into the duodenum). Also, hormone production (endocrine action), from Islets of Langerhans.
• ~ 1% endocrine tissue, 99% exocrine tissue
What are the major cell types in the islets and what do they secrete?
Beta cells- insulin alpha cells- glucagon delta cells- somatostatin PP cells- PP e cells- gherkin g cells- gastrin
Why is plasma glucose important and what are reference values for plasma glucose?
Brain uses glucose at fastest rate in body. Relies on blood and sensitive to falls and rises in glucose.
Normally 3.3-6 mmol/L (UHL reference range)
After a meal 7-8 mmol/L
Renal threshold 10 mmol/L
– Glycosuria
- Pregnancy: renal threshold↓
- Elderly: renal threshold↑
What are some properties of insulin and glucagon?
Water soluble hormones: • Carried dissolved in plasma – no special transport proteins • Short ½ life 5mins • interact with cell surface receptors on target cells.
• receptor with hormone bound can be internalised – inactivation.
What are the metabolic properties of insulin?
- Anabolic
- anti-gluconeogentic
- anti-lipolytic and anti-ketotonic
- in its action (favours storage) it is the hormone of energy storage
Describe insulin’s structure
alpha helix structure (3bits)
consists of two un-branched peptide chains which are connected by 2 disulfide bridges this ensure stability (hold chains together)
note- c peptide helps prevent vascular damage
How are Katp channels regulated by metabolism?
inhibited by ATP.
Katp channels not inhibited under normal conditions and therefore this is hyper polarised membrane potential. when glucose added, membrane depolarises as ATP starts being produced again (due to glucose) and potassium channels close.
when Katp channels are shut, insulin is secreted as membrane depolarisation activates VOCC’s and this causes calcium mediated release of insulin.
What are the effects of insulin in different tissues?
increases glucose uptake into target cells and glycogen synthesis
(insertion of Glut 4 channel )
– in the liver it increases glycogen synthesis by stimulating
glycogen formation and by inhibiting breakdown – in muscles it increase uptake of AA promoting protein synthesis – in liver inhibits breakdown of AA
– in adipose tissue increases the storage of triglycerides and inhibits fatty acid breakdown
What are the metabolic effects of glucagon?
Hormone that opposes insulin
– acts to raise blood glucose levels – It is glycogenolytic, – gluconeogenetic – lipolytic – ketogenic-
• it mobilizes energy release
When is glucagon released`?
Secreted by α- cells • Secreted due to low glucose levels in α-cells • Synthesized in Rough ER transported to Golgi • package in granules • Effect mainly in the liver
How is diabetes diagnosed?
normal range 3.3-6mmol/L plasma glucose (UHL reference
range) • fasting ≥ 7.0mM • random ≥ 11.1mM
What is the difference between type 1 and type 2 diabetes?
Type 1 – absolute insulin
deficiency (Autoimmune
destruction of Pancreatic β-
cells).
Type 2 –secretion but
relative peripheral insulin resistance.
– Defective insulin receptor mechanism – change in receptor number and/or affinity. – Defective post-receptor events. e.g. Insulin resistance – tissues become insensitive to insulin. – Or Excessive or inappropriate glucagon secretion
How does insulin resistance in the young lead to diabetes?
Initially:
–β
-cells compensate by increasing insulin production - maintains normal blood glucose.
• Eventually:
– β-cells unable to maintain increased insulin production -
impaired glucose tolerance.
• Finally:
– β-cell dysfunction leads to relative insulin deficiency - overt
type 2 diabetes
What causes diabetic ketoacidosis?
- high rate of beta oxidation of fats in the liver as beta oxidation coupled to low insulin:anti-insulin ratio
- low insulin so lipolysis increases serum free fatty acids. Hepatic metabolism of free fatty acids as an alternative energy source (ie, ketogenesis) results in accumulation of acidic intermediate and end metabolites (ie, ketones)
What are the symptoms of diabetic ketoacidosis?
- frequent urination.
- extreme thirst.
- nausea.
- vomiting.
- abdominal pain.
- confusion.
- breath that smells fruity.
