Lecture 31 Flashcards
What are the cells and their functions in the Islets of Langerhans?
B-Cells which secrete insulin
A-Cells which secrete glucagon
D-Cells which secrete somatostatin
What is the function of the insulin hormone?
Fuel-Storage Hormone
Decreases Blood glucose through increasing glucose uptake into muscle and fat, increasing glycogen synthesis
Decreasing gluconeogenesis, decreasing glycogen breakdown
What is the function of the glucagon hormone?
Fuel Mobilizing hormone
Stimulates gluconeogenesis, glycogenolysis and lipolysis
What do B cells respond to?
B-Cells release a steady basal rate of insulin and respond to changes in both rate and absolute concentration of glucose
What is the two-phase release of insulin by B Cells?
An initial rapid phase of insulin release reflecting release of stored hormone
A slower, delayed phase reflecting both continued release of stored hormone and new synthesis
How do B-Cells release insulin?
ATP-Sensitive K+ channels are used to determine the cells resting membrane potential
Glucose enters the cell and is metabolised by glucokinase and glycolysis to increase intracellular ATP
This blocks the K+ ATP sensitive channels causing membrane depolarisation leading to the opening of voltage sensitive Ca2+ channels
The increase in Ca2+ acts as a signal inducing insulin secretion
How does insulin act on its target cells?
Activates a tyrosine kinase receptor leading to a larger number of second messengers to trigger its effect
What are the two types of diabetes mellitus?
Insulin dependent diabetes mellitus (Type I)
Insulin independent diabetes mellitus (Type II)
What causes type I diabetes?
There is a degeneration (believed to be autoimmune derived) of pancreatic B-Cells which produce insulin
Has an abrupt clinical onset (though the actual degeneration may have occurred for years previously)
Why is type I diabetes generally considered to be the more serious condition?
There is hyperglycemia where the liver and muscle cannot store glycogen and tissues are unable to take up and utilize glucose
There is ketosis (ketone formation) where fatty acid synthesis inhibition leads to ketone formation (metabolic acidosis) causing the formation of aceto-acetate, Beta-hydroxybutyrate, Acetone
This can cause a diabetic coma and even death
What are the aims of insulin therapy for type I diabetes?
Minimise the occurrence of hyperglycemia
Prevent development of long term complications of diabetes
Extend the lifespan and improve the quality of life
How has treatment of type I diabetes developed?
Patients are dependant on administration of exogenous insulin
Initially this insulin was pork of beef insulin but this was poorly tolerated due to a slightly different amino acid sequence
Today patients are given human insulin produced via recombinant yeast which is better tolerated and has a lower risk of disease such as BSE
What are the different ways in which the insulin treatments for type I diabetics can be delivered?
Subcutaneous injection
Jet-injection
By pump
Oral delivery is being experimented with but as most hormone seems to be destroyed by proteases in the gut before it can be absorbed only the injection method works
What is Humalog?
A very fast acting insulin treatment which lowers blood sugars for 45-90 minutes and stops acting after 3-4 hours
What is Humulin?
A fast acting insulin treatment which lowers blood sugars for 2-5 hours and stops acting after 5-8 hours
What is NPH/Lente?
An intermediate acting insulin treatment which lowers blood sugars for 6-12 hours and stops acting after 28 hours
What is Ultralente?
A long acting insulin treatment which prolongs the entry of insulin into the blood stream for 4-6 hours and stops acting after 28 hours
What is glargine?
An ultra-long insulin treatment which works at a relatively constant rate for 24 hours
What is the purpose of having so many different forms of insulin treatment available?
Allows the patient to mix and match treatments to allow for flexibility and a more normal lifestyle
What causes insulin independent diabetes?
Insensitivity of target cells to insulin known as insulin resistence
This can develop from a reduced number of insulin receptors or a problem in the pathway of insulin action such as a misfunctioning second messenger
What are the treatments for type II diabetes?
Oral hypoglycemic agents such as sulfonylureas like tolbutamide and Meglitinides as well as Biguanides such as metformin
What is the mechanism of action of sulfonylureas and meglitinides?
Have the same mechanism
Increase Insulin release as there are high affinity receptors for sulfonureas and meglitinides (though different sites respectively) of the K+(ATP) in B-Cells
These block the K+(ATP) allowing the B cells to still depolarise and release insulin
They also appear to increase insulin sensitivity though the mechanism for this is unknown
What is notable about the two phase insulin release in diabetics compared to non-diabetics?
Type I diabetes has no increase in insulin levels
Type II diabetes does have basal insulin secretion sometimes even higher than that of non-diabetics but lacks the rapid phase 1 response
What is the mechanism of action of metformin?
Reduces hepatic glucose production through activation of AMP-activated protein kinase
This also increases glucose uptake and utilization in skeletal muscle
