The Endocrine Pancreas Flashcards
What are the different islet endocrine cell types?
alpha-cells
beta-cells
delta-cells secrete somatostatin
PP-cells secrete pancreatic polypeptide
epsilon-cells secrete Ghrelin
What is the role of pancratic ACINI?
The functional units of the pancreas that produce and secrete DIGESTIVE enzymes.
These enzymes are released into the pancreatic ducts, which then transport them to the duodenum
How is the pancrease both an endocrine and exocrine organ?
The endocrine pancreas refers to the part of the pancreas that produces hormones, primarily insulin and glucagon, which regulate blood sugar levels, while the exocrine pancreas produces digestive enzymes that are secreted into the small intestine to aid in food digestion; essentially, the endocrine pancreas controls blood sugar through hormones, while the exocrine pancreas helps with digestion through enzymes
What is the difference between mouse and human iselt architecture?
Mice have a continuous core of beta cells
Humans have scattered beta cells
What is the same between mouse and human islset architecture?
In both organisms, beta-cells are the most numerous islet cell
What is the range of normal blood glucose levels?
4.5 to 7.5 mmol per L
How can beta cells compensate for insulin resistance?
By releasing more insulin
What is normally associated with increased adiposity?
Insulin resistance
Define insulin sensitivity
Insulin sensitivity is how well your body responds to insulin, a hormone that controls blood sugar levels. Insulin resistance is when your body is less sensitive to insulin, and you need more insulin to lower your blood sugar.
What is the relationship between insulin secretion and insulin sensitivity to maintain glucose homeostasis?
To stay in normal range
If insulin sensitive then so long as insulin release is not too low = will stay in normal range
If insulin resistant need much higher insulin release to stay in normal range
What is Hba1c?***
Glycated haemoglobin = Hb bound to glucose
Better marker for long-term glycaemic control than fasting plasma glucose
When blood glucose levels are high, glucose molecules attach to hemoglobin in red blood cells.
The higher the blood glucose levels, the more glucose binds to hemoglobin, resulting in higher levels of HbA1c.
Since red blood cells typically have a lifespan of about 120 days, the amount of HbA1c reflects a person’s average blood sugar levels over the past few months.
What are the normal ranges and diabetic ranges of Hba1c?
Normal: Below 5.7%
Prediabetes: 5.7% to 6.4%
Diabetes: 6.5% or higher (diagnostic criteria)
What are the risk factors for T2DM?
Genetic factors = most for beta-cell genes
Environmental factors = mostly increasing demand for insulin
Epigenetic factors = maternal and paternal metabolic health influences offspring T2DM risk
What are therapeutic strategies for T1D?
High levels of beta cell loss due to autoimme disease
Protect beta cell form destruction in stage 1+2
Replace or regenerate beta cells in stage 3
Why is T2D dangerous?
Causes complications because of abnormal glycosylation of proteins in the presenece of high glucose = making cells behave abnormally
What is the difference between glycation and glycosylations?
Glucation = non-enzymatic glycosulation = unregulated covalent bonding of a protein/lipid like sugars
Glycosylation = enzyme-controlled addition of sugars to protein/lipids
How is insulin secretion stimulated?
High blood glucose
GLUT1/2
Glucokinase and Oxidative metabolism = ATP
K_ATP channels close (membrane no longer negative)
L-type v.g Ca2+ channels
Exocytotic machinery (SNARE proteins)
Why is glucokinase found in pancreas and liver, nor hexokinase?
Glucokinase has higher Km so lower affinity, making it more responsive to higher glucose levels
What does Km of glucokinase tell us?
50% activity occurs at a higher glucose concentration
How do we know glucose must be metabolised to stimulate insulin secretion?
Can inhibit an enzyme that metabolizes glucose
Inhibit glucokinase using MANOHEPTULOSE
Stopping glucokinase = stop insulin secretion
What is the role of K_ATP channel when it is open?
Maintain hyperpolarized plasma membrane
Describe the graph of insulin secretion
Insulin secretion is BIPHASIC
Phase 1 insulin secretion = primes muscle and adipose glucose uptake
Phase 2 insulin secretion = more vesicles recruited to membrane
What phase of insulin secretion is disrupted in T2D?
Phase 1 insulin secretion can malfunciton = uptake to muscle and adipose
Used as a markers to show beta-cell function issues
What is the role of glucagon and its target?
Pancreatic a-cell releases glucagon
Targets liver to stimulate gluconeogenesis and glycogenolysis
How do alpha-cells respond when glucose is high?
Glucose uptake and metabolism to ATP causes K_ATP channel to close = cell depolarizes
Present of SGLT2 glucose transporters = non-voltage regulated Na+ influx
NaV and CaV channels close = glucagon NOT exocytosed
How do alpha-cell respond when glucose is low?***
Glucose uptake and metabolism low
So K_ATP channels is open
Voltage-gated Na+ channels contribute to action potential
P/Q type v.g Ca+ channels enable calcium influx
Glucagon exocytosis TRIGGERED
What are glucagon levels like in T2D?
Glucagon levels stay high after FASTING and feeding
Exacerbating hyperglycaemia because liver still produces more glucose
When glucagon action was removed by removing glucagon receptors = blood glucose levels dropped
Define exocrine
Secreted outside of the body using ducts
Define endocrine
Secreted into the bloodstream
Describe paracrine
Signal secreted and targets cell receptors nearby
Describe autocine
Cell secretes signal and targets its own receptors
Describe juxtacrine
Ligand on membrane of cell physically binds neighbouring cell to signal
What is the role of somatostatin and by what signalling manner?
Suppresses beta and alpha cell funciton = paracrine manner
What triggers somatostatin release by delta-cell?
Nutrient or homronal stimulation
