Endocrine Pancreas Flashcards
Endocrine functions of the pancreas play a large role in regulating metabolism for which molecules?
Lipids, CHOs, and Amino Acids
How are the endocrine cells of the pancreas arranged?
They are arranged in clusters called Islets of Langerhans; they comprise ~1-2% of the pancreatic mass, containing around 2500 cells.
Innervation for the Islet cells
Adrenergic, cholinergic, and peptidergic neurons
Describe Beta cells
They comprise 60-65% of each Islet. They are centrally located and receive the frist blood supply. They secrete insulin and C peptide.
Describe Alpha cells
They comprise about 20% of the Islet and are located predominantly around the periphery of the Islet. Alpha cells secrete glucagon.
Describe the Islet cells that are not Alpha or Beta cells.
Delta cells comprise ~5% of the Islets; they are interspersed between alpha and beta cells, mostly toward the periphery of the Islet. The secrete somatostatin and are neuronal in appearance with dendrite-like processes extening to Beta cells.
F Cells (PP Cells) secrete pancreatic polypeptide, acting as a satiety signal (neuropeptide Y, peptide YY family)
Describe Islet Cell communication and blood flow
Gap junctions between cells allow for rapid cell-to-cell communication (a-a, b-b, a-b)
The islets receive 10% of pancreatic blood flow. Venous blood begins at the center of the Islet and moves toward the periphery, allowing one cell type to bathe other cell types; Venous blood from Beta-cells carry insulin to Alpha and Delta Cells. Blood first to the center with high Beta-cell concentrations allows for the flow of Insulin to flow first, inhibiting glucagon release from the Alpha cells.
(The paracrine functions act in reverse of blood flow)
Insulin: catabolic or anabolic?
Insulin is a MAJOR anabolic hormone with glucose acting as the major stimulatory factor. When Insulin isn’t released as in T2DM, the affected individulas become cachexic-looking d/t the catabolic activity d/t no insuling acting to uptake glucose
Describe insulin the hormone
Insulin is a peptide hormone made of two chains, linked by disulfide bridges.
Preporinsulin –> Proinsulin –> Insulin & C peptide
Preproinsulin: signal peptide with A & B chains w/ connecting peptide (C Peptide) - no disulfide bonds
Proinsulin: no signal peptide; C peptide is removed once packaged in the Golgi–> Golgi packages into secretory granules where proteases cleave the C Peptide. C peptide remains in the granule and is secreted with the insulin molecule
8 steps of insulin release
- Glucose enters cell via GLUT-2
2 Glucose is phosphorylated to G-6-P by glucokinase
- G-6-P is Oxidized, promoting ATP generation
- ATP closes the “inward-rectifying” K+ channel
- Plasma membrane is depolarized
- Activation of voltage-gated Ca2+ channels
7-8. Ca2+ enters the cell and initiates mobilization of insulin (& C peptide) containing vesicles to plasma membrane and exocytosis
What catalyzes the closing of the K+ channels?
A rise in ATP via the ATP-dependent K+ channels
What is the action of sulfonylurea drugs?
Sulfonylurea drugs stimulate insulin release from Beta-cells by closing the ATP-dependent K+ channels, depolarizing the cell, and mimicking the depolarization induced by glucose.
What can be used as a non-invasive tool to guage endogenous insulin secretion?
The measure of C Peptide in urine
How is insulin secretion related to blood glucose?
“Insulin secretion is basically proportional to plasma glucose changes”
Insulin response graph
Insulin release is biphasic with an immediate realease after food intake then a drop and gradual rise over time; this all occurs over 1-2 hours
