Biochemistry Flashcards
What are the various types of cells which are found in the pancreatic islets of langherhans?
alpha cells
beta cells
delta cells
PP cells
What do each cell found in the islets of langerhans secrete
beta cells - insulin
alpha cells - glucagon
delta cells - somatostatin
PP cells - pancreatic polypeptide
Where is insulin synthesised?
rough endoplasmic reticulum of pancreatic beta cells
What is the precursor for insulin?
larger single chain preprohormone called preproinsulin
Briefly describe the structure of insulin
two polypeptide chains linked by disulfide bonds
Name the other by-product of insulin cleavage
C Peptide
How are insulin preparations classified?
Ultra fast/ultra short-acting Short-acting Intermediate-acting Long-acting Ultra long-acting
How long after a meal should Insulin Lispro be injected into the body?
Within 15 minutes of beginning a meal
Should ultra-fast acting insulin be used in Type 1 diabetes management?
Must be used in combination with longer-acting preparation
unless used for continuous infusion
What classification of insulin is glargine and when should this be administered?
Ultra-long acting
Administered as a single bedtime dose
What transporter is responsible for glucose uptake into the cell?
GLUT 2
What enzyme is responsible for the phosphorylation of glucose to Gluco-6-phosphate once it enters the cell?
Glucokinase
Describe the physiology of insulin release
Glucose into cell Glucose metabolism = ATP generation ATP inhibits K+ into cell Membrane depolarises (closer to 0) Opens Voltage Gated Ca2+ Channel Ca2+ In Vesicles fuse with membrane Release insulin
What threshold must be met for Beta cells to release insulin?
blood glucose rising above 5 mM
What is meant by “the cells lose the ability to sense glucose?”
hyperglyceamia takes glucose concentration outwith the Km of glucokinase
Describe the graphic nature of insulin release
Biphasic
First peak is higher than second
What are the two pools in which insulin is released?
RRP – readily releasable pool (5 %)
Reserve pool
What type of drug is used in Type 2 Diabetes to stimulate insulin secretion from beta cells
sulphonylurea drugs mimic the action of ATP to depolarise beta cells.
What patients are sulphonylurea drugs most appropriate for in Type 2 Diabetes treatment
- patients who have trouble injecting insulin
- patient has improved their glucose control and lessened the stress on the islet.
What two subunits make up the K+ ATP channels?
Kir6.2 and SUR1
What can mutations in either of the two K+ ATP channel subunits result in?
Neonatal diabetes
What is MODY?
Maturity-onset diabetes of the young (MODY)
- genetic defect in beta cell function (6 mutations)
- Familial form of early-onset Type 2 diabetes
- defect in insulin secretion not damaged beta cells
What are the functions of HNF transcription factors?
- pancreas foetal development and neogenesis
- regulate b cell differentiation and function
Why must screening to differentiate between Type 1 diabetes and MODY be robust?
Allows treatment of MODY with sulphonylurea rather than insulin (as they usually have some b-cell function available)
Describe the difference between Type 1 diabetes, Type 2 Diabetes and MODY
Type 1 Diabetes – Loss of insulin secreting beta cells
MODY- defective glucose sensing in the pancreas and/or loss of insulin secretion
Type 2 Diabetes- Initially hyperglycemia with hyperinsulinemia => reduced insulin sensitivity in tissues
What processes does insulin turn OFF (as an anabolic hormone)?
Lipolysis
Gluconeogenesis in liver
What processes does insulin stimulate?
Amino acid uptake in muscle DNA/Protein synthesis Glucose uptake in muscle and adipose tissue Lipogenesis in adipose tissue and liver Glycogen synthesis in liver and muscle
What type of receptor does insulin bind to?
Receptor Tyrosine Kinase
What are the two main pathways via which insulin can signal?
PKB
Ras
What is Leprechaunism/ Donohue Syndrome?
- Rare autosomal recessive genetic trait
- Mutations in the gene for the insulin receptor
- Severe insulin resistance
What developmental abnormalities can be present in Leprechaunism/ Donohue Syndrome?
- elfin facial appearance
- growth retardation
- absence of subcutaneous fat, decreased muscle mass
What is Rabson Mendenhall Syndrome?
- Rare autosomal recessive genetic trait
- Severe insulin resistance
- hyperglycemia and compensatory hyperinsulinemia
- Diabetic ketoacidosis can occur
What developmental abnormality can be seen in Rabson Mendenhall syndrome?
Acanthosis nigricans (hyperpigmentation)
When is Diabetic ketoacidosis a danger in Type 1 diabetes?
If an insulin dose is missed
