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58 Cards in this Set

  • Front
  • Back
Describe the development of the pancreas by week 4.
Two outpocketings from the endodermal lining of the duodenum form the ventral and dorsal pancreas.
What structures are derived from the ventral pancreas?
1. Part of head
2. Common bile duct
What structures are derived from the dorsal pancreas?
1. Part of the head
2. Body
3. Tail
Describe the development of the pancreas by week 12.
Pancreatic acini develop from the ducts.
T or F

Endocrine pancreas develops at the same time as exocrine pancreas
TRUE
When are endocrine cells first observed in the developing pancreas?
Between weeks 12 - 16.
(observed along the base of differentiating exocrine acini)
Each islet of Langerhan is made of which two components?
1. Anastomosing cords of endocrine cells
2. Insuloacinar portal system (vascular component)
What is the function of the insuloacinar portal system?
Enables local action of insulohormones on the exocrine pancreas
What do delta cells secrete?
1. Gastrin
2. Somatostatin
What do F cells secrete?
Pancreatic polypeptide
How does glucagon increase blood glucose levels?
Promotes hepatic glycogenolosis
Describe the structure of insulin.
Two chains (A and B) linked by disulfide bond
Describe the synthesis of insulin.
1. Preproinsulin is the large single-chain precursor (includes signal sequence that directs the compound to the ER)
2. Signal sequence cleaved --> proinsulin is directed to Golgi apparatus. Proinsulin consists of A, B chains and C-peptide
3. C-peptide is cleaved in Gogli, separating A and B chains.
Describe the resulting structure when C-peptide is removed during insulin synthesis.
A and B chains are separated.
Organization of a crystalline core consisting of a hexamer and zinc atoms. C-peptide surrounds the core
How is glucose taken up by B-cells?
GLUT2 (insulin-independent transporter)
Describe the structure of the insulin receptor.
Two subunits:
1. a-subunit: insulin binding site
2. b-subunit: tyrosine kinase activity (autophosphorylation)
How does the interaction between insulin and the insulin receptor result in increased glucose uptake?
Intracellular phosphorylation events lead to upregulation of GLUT4 receptors which get incorporated into the plasma membrane.
Where are GLUT2 receptors found?
1. Liver
2. B-cells of pancreas
Where are GLUT4 receptors found?
1. Adipose tissue
2. Skeletal M
3. Cardiac M
Which glucose receptor serves to remove glucose from the blood?
GLUT4
In which organs can glucagon be found?
1. Pancreas
2. GI tract
3. Brain
Which organ is the primary target site of glucagon?
Liver
Why does glucagon induce hyperglycemia?
By promoting glycogenolysis in hepatocytes
Are Zinc and C-peptide present in insulin, glucagon, or both?
Only insulin
The secretion of glucagon is stimulated by..?
1. Fall in blood glucose concentration
2. Increase in arginine and alanine
3. Stimulation of sympathetic NS
What is the effect of somatostatin on insulin and glucagon?
Inhibits secretion of insulin and glucagon
List 4 inhibitory effects of somatostatin.
Inhibits:
1. insulin, glucagon secretion
2. bicarbonate and pancreatic enzyme release
3. HCl secretion by parietal cells
4. Gallbladder contraction
Where is somatostatin produced?
1. Upper digestive tract
2. Hypothalamus
What is the effect of somatostatin produced by the hypothalamus?
Inhibits the secretion of growth hormone from the anterior hypophysis.
What peptide inhibits somatostatin?
Pancreatic polypeptide
(produced by F cells)
List 3 inhibitory effects of pancreatic polypeptide.
Inhibits:
1. Somatostatin release
2. Pancreatic enzymes
3. Gall bladder contraction (bile secretion)
What hormone stimulates the release of pancreatic polypeptide?
Cholecystokinin
How can cell types in the islets of Langerhans be identified? (3 ways)
1. Immunochemistry (antibodies)
2. Electron microscopy (size, structure)
3. Cell distribution in the islet
What is the key regulator of insulin release?
ATP-sensitive K+ channel
ATP-sensitive K+ channel is composed of what subunits?
1. SUR1 (sulfonylurea receptor 1)
2. Kir6.2 (inward-rectifying K+ channel)
Describe the K-ATP channel in the normal, resting state.
K-ATP channel is open and the voltage-gated Ca2+ channel is closed.
*No insulin is secreted
Describe what happens to the K-ATP channel when glucose is taken up by B cells.
K-ATP channel closes and K+ builds up within the cell. This results in membrane depolarization, causing Ca2+ channels to open.
*Influx of Ca2+ triggers insulin exocytosis
Gain of function and loss of function mutations can occur in genes coding for what subunits?
SUR1 and Kir6.2 (subunits of the ATP-sensitive K+ channel complex)
What is the result of gain-of-function mutations in SUR1 and Kir6.2?

What disease is this sort of mutation associated with?
K+-ATP channel remains open, thereby decreasing insulin secretion

*Neonatal diabetes mellitus
What is the result of loss-of-function mutations in SUR1 and Kir6.2?

What disease is a consequence of this mutation?
K+-ATP channel is closed, resulting in continued Ca2+ influx and unregulated insulin secretion.

*Neonatal hyperinsulinemic hypoglycemia
What can cause Type 1 diabetes?
1. Autoimmune destruction of B cells
2. Toxic or viral damage to B cells

(Results in lack of insulin)
What is insulinitis? What is it characteristic of?
Infiltration of lymphocytes, characteristic of early stages of IDDM.
Lack of responsiveness to insulin by target cells can be caused by what 2 cellular abnormalities?

Which defect is most frequent?
1. Decrease in number of available insulin receptors
2. Deficiency in postreceptor signaling <--Most frequent (80%).
List 3 characteristic symptoms of both Type 1 and Type 2 diabetes.
1. Hyperglycemia
2. Polyuria
3. Polydispia
Where does the thyroid gland develop from?
Endodermal downgrowth at the base of the tongue, connected by the thryoglossal duct.
C-cells in the thyroid gland are derived from what type of cells?
Neural crest cells
What is the precursor of thyroid hormones?
Thyroglobulin
What are the two thyroid hormones?
Triiodothyronine (T3)
Thyroxine (T4)
What is the main function of the thyroid gland?
Maintain body's basal metabolism
What are the 2 phases of thyroid hormone synthesis and secretion?

What are these phases regulated by?
1. Exocrine phase
2. Endocrine phase

*Regulated by thyroid stimulating hormone (TSH)
Where is TSH produced?
Basophil cells in anterior hypophysis
What does the exocrine phase of thyroid hormone production consist of?
1. Synthesis and secretion of thyroglobulin into colloid-containing lumen
2. Uptake of inorganic iodide from blood through an ATP-dependent iodide pump.
What enzyme converts iodide to iodine?
Thyroid peroxidase
How are iodine atoms attached to thyroglobulin?
Iodine atoms are attached to tyrosil residues on thyroglobuin, which become iodothyroglobulin
What does the endocrine phase of thyroid hormone production consist of?
1. Reuptake and processing of iodothyroglobulin into colloid droplets
2. Colloid droplets enveloped by pseudopods to become vesicles
3. Lysosomes fuse with the vesicles
4. Iodothyroglobulin is processed to release T3 and T4 into bloodstream
How are T3 and T4 transported in the bloodstream?
By serum carrier proteins
At what site are thyroid hormones directed into cells and what element do they bind to?
Enter cell nucleus.
Bind to thyroid hormone-responsive element
**Activates gene expression
What is a Kimmelstiel-Wilson lesion?
Glomerulopathy
(thickening of the gomerular basal lamina of glomerular capillaries, and proliferation of of cells affecting glomerular filtration of the kidneys)