[11.06] Endocrine Pancreas V2.pdf

Exocrine (Acini)

What is the exocrine portion of the pancreas called?

Digestive juices into the duodenum

What do the acini secrete and where do they secrete it?

Digestion

What is the role of the secretions from the acini?

Endocrine (Islets of Langerhans)

What is the endocrine portion of the pancreas called?

Hormones directly into the bloodstream

What do the Islets of Langerhans secrete and where do they secrete it?

About 3 million

Approximately how many islets are in the pancreas?

Less than 3%

What percentage of the pancreas do the islets constitute?

About 1 gram

Approximately what is the weight contribution of the islets to the pancreas?

Rich vascularization

Despite being less than 3% of pancreatic weight, what kind of blood supply do the islets receive?

10%

What percentage of the pancreatic blood flow do the islets receive?

Adrenergic, cholinergic, and peptidergic

What are the three main types of neurons that richly innervate the islet cells?

Multiple regulation mechanisms

Why is the rich innervation of the endocrine pancreas important?

Beta, Alpha, Delta, γ, ε

What are the five cell types associated with the Islets of Langerhans?

Pancreatic polypeptide

What does the γ cell produce?

Ghrelin

What does the ε cell produce?

Beta cell

Which islet cell type is considered the most important?

60%

What percentage of all islet cells do beta cells constitute?

Insulin and amylin

What two hormones do beta cells produce?

Alpha cell

Which islet cell type constitutes 25% of all islet cells?

Glucagon

What hormone do alpha cells produce?

Delta cell

Which islet cell type constitutes 10% of all islet cells?

Somatostatin

What hormone do delta cells produce?

Widely distributed

How is the distribution of delta cells described in the body?

Various functions

What is noted about the functions of somatostatin in the body?

Small capillaries

Around what structures are islets arranged into which hormones are secreted?

Directly into the bloodstream

Where do islet cells secrete their hormones?

Distinct population of cells surrounded by pancreatic acini

Describe the structural relationship between the Islets of Langerhans and the pancreatic acini.

Admixed together

How are the endocrine and exocrine portions of the pancreas structurally related?

Venous blood from one cell type bathes other cell types

Due to their proximity, what happens with the venous blood in the islets?

Paracrine regulation

What is the significance of the venous blood flow bathing other cell types in the islets?

Gap junctions

What structures interconnect the islet cells, allowing for cell-to-cell communication?

Cell to cell communication and paracrine modulation

What is the importance of the close interrelations between islet cells?

Autocrine and paracrine effects

What types of effects are present in the islets to ensure blood glucose levels remain in the normal range?

Insulin inhibits glucagon secretion

Provide an example of paracrine modulation within the islets regarding insulin and glucagon.

Amylin inhibits insulin secretion

Provide another example of paracrine modulation within the islets regarding amylin and insulin.

Somatostatin inhibits insulin and glucagon secretion

Provide another example of paracrine modulation within the islets regarding somatostatin, insulin, and glucagon.

Prevent too much hyperglycemia or hypoglycemia

What is the role of these multiple regulatory elements in blood glucose control?

Decrease blood glucose concentration

What is the primary goal of insulin?

Excess energy to be stored

During what period is insulin typically secreted?

Storing any extra glucose or energy anywhere

How does insulin lower blood glucose concentration?

Hormone's function

According to Doc Uy-Canto, what should you always go back to when trying to understand a hormone's mechanism?

Preproinsulin

What is the initial translation product of RNA when a signal comes to make more insulin?

Signal peptide and A, B, C peptide chain of mature insulin

What components does preproinsulin include?

Endoplasmic reticulum

Where does the translation of RNA into preproinsulin occur?

Proinsulin

What is formed when the signal chain is cut off from preproinsulin?

A, B, C peptide chains

What peptide chains does proinsulin contain?

Conformational changes and disulfide bridges

What happens to proinsulin in terms of its structure?

Golgi apparatus

Where does the cleavage of proinsulin occur?

C-peptide

What is removed from proinsulin during cleavage?

Connected A and B chain

What does mature insulin consist of after cleavage?

Secretory granule

In what structure is mature insulin packaged before secretion?

Portal circulation

Into where is insulin secreted once it is ready to be released?

Mainly insulin

What is the main component of beta cell secretion?

5-10% proinsulin

What percentage of the final product of beta cells is proinsulin?

Virtually no insulin activity

What is the insulin activity of proinsulin and C-peptide?

Measure endogenous function through radioimmunoassay

Why is C-peptide clinically significant despite having no insulin activity?

Secretion - Clearance

How can insulin concentration be described in terms of secretion and clearance?

Portal circulation

Where does most insulin clearance happen?

First-pass hepatic metabolism

What process in the liver extracts a large amount of insulin, making its measurement difficult?

Released in an equimolar amount with insulin, not extracted by the liver, undergoes constant kidney clearance

What are the reasons why C-peptide is used to measure endogenous insulin production?

Endogenous (synthesized inside the body)

What type of insulin production can C-peptide levels help determine?

Exogenous (pharmaceutical)

What type of insulin will NOT have C-peptide associated with it?

Insulinoma

What is a pancreatic mass producing lots of insulin called?

Endogenous or exogenous source of excessive insulin in hypoglycemic patients

What can C-peptide help determine in very hypoglycemic patients?

Human insulin

Why is C-peptide more relevant now in differentiating endogenous and exogenous insulin sources?

False

T/F: Alpha cells produce amylin.

Somatostatin

Delta cells produce ?

False

T/F: 5-10% of beta cell’s final product consists of preproinsulin.

Golgi apparatus

Where is proinsulin cleaved?

2 amino acid chains (A and B) connected by disulfide linkages or bridges

What is the structure of insulin?

Loss of functional activity

What happens if the disulfide linkages in insulin are broken?

Unbound form

In what form does insulin circulate in the blood?

6 minutes

What is the plasma half-life of insulin?

Minute-to-minute regulation

Why is the short half-life of insulin important?

Insulinase

What enzyme mainly degrades the remaining insulin?

Liver, kidneys, and muscles

Where is insulinase mainly found?

Breaks disulfide bonds

How does insulinase degrade insulin?

Inactive A and B chains excreted in the urine

What are the products of insulin degradation and where are they excreted?

Functional insulin-secreting beta cells, ability to sense ambient glucose concentration

What are the key requirements for insulin secretion?

Quality of beta cell mass, architecture and structural integrity

What are the two aspects of functional insulin-secreting beta cells mentioned?

Allows cell to cell communication

Why is the architecture and structural integrity of beta cells important for insulin secretion?

Ambient glucose concentration

What should beta cells be able to sense for good insulin secretion?

Glucose

What is the key regulator of insulin secretion?

70 mg/dL (3.9 mmol/L)

What blood glucose concentration will stimulate insulin synthesis?

Large functional reserve

What is noted about the reserve capacity of beta cells for insulin secretion?

200-250 units

Approximately how much insulin can beta cells secrete?

Made, stored, and then released when needed

How does insulin secretion differ from steroid hormone production in terms of synthesis and release?

10 day supply for a lean adult

Approximately how long can the insulin reserve in beta cells last for a lean adult?

Islet neogenesis, beta cell proliferation, and beta cell hyperplasia

What are the three processes that determine beta cell mass?

In-utero

When does most fetal neogenesis of beta cells from ductal epithelial precursors occur?

Burst of neonatal beta cell replication

What happens to beta cell replication in the neonatal period?

Almost complete at 5 y/o

When is beta cell mass almost fully developed?

Low beta cell proliferation

What is the rate of beta cell proliferation throughout adulthood?

Small subset of cell population that serves as reservoir

What exists to replenish beta cells in adulthood?

Apoptosis and dedifferentiation

What happens to beta cells as one ages?

How much is made and how much is dying

What determines the function of beta cell mass?

Abundant GLUT2 transporters scattered in the beta cells, rich islet cell vascularization (fenestrated vessels)

What are the two ways the pancreas can sense ambient glucose?

Signal can come in and secretion can come out

What is the significance of the fenestrated vessels in islet vascularization for glucose sensing and insulin secretion?

Glucose, leucine, parasympathetic (M3 acetylcholine), sulfonylureas, enteric hormones (GLP, GIP, CCK, secretin, gastrin), neural (β-adrenergic), amino acids (arginine)

List the stimulants of insulin release mentioned in Table 1.

Enteric hormones (GLP, GIP, CCK, secretin, gastrin)

Which category of stimulants of insulin release enhances insulin release in the presence of ingested glucose?