Pancreas Flashcards
What hormones does the pancreas release?
Insulin
Glucagon
Somatostatin (FYI)
What are the 2 purpose of regulating blood glucose?
- Source of energy (cellular function) and brain function
*Brain does not store glycogen, depend solely on blood glucose - Store for later use (via action of insulin, glucose stored as glycogen in liver and muscles)
*Others: TGL stored in adipose tissue, protein stored in muscles
Where is the pancreas located?
Behind stomach, head of pancreas on the right side
Connected to duodenum through pancreatic duct
What are the cell types in islet of Langerhans and what do they produce?
alpha cells (20%) - glucagon
beta cells (70%) - insulin
delta cells - somatostatin
F cell/pp cell - pancreatic polypeptide
Process of insulin secretion is known as excitation-secretion coupling
How is insulin released from B cells?
- Glucose enter B cell via GLUT2 transporter (passive facilitated diffusion)
- In cell, glucose is phosphorylated to glucose-6-phosphate
- G-6-P feeds into Krebs cycle in the mitochondria, oxidation occurs, ATP generated
- ATP acts on ATP-sensitive K+ channel, thus closing it
- Increase K+ in cell as less is able to leave (depolarization of cell) [EXCITATION]
- Depolarization causes opening of the voltage gated Ca2+ channel
- Secrete Ca2+ into cell [SECRETION]
- Insulin vesicles release insulin out of cell
What is the purpose of phosphorylation of glucose inside the B cell?
Traps glucose in the cell, while keeping a low intracellular ‘glucose’ level, thus maintaining diffusion gradient to allow more glucose to enter the cell via passive facilitated diffusion through GLUT2 transporter
What is the primary stimulation for insulin release/secretion?
Increase blood glucose level
Insulin increases cell (liver, muscle, adipose tissue etc.) uptake of glucose
Where are each of the GLUT transporters found?
GLUT1 - endothelial cells of BBB
GLUT2 - pancreatic B cells, liver, kidney, SGLT
GLUT3 - neurons
GLUT4 - muscle and adipose tissue
GLUT1, 2, 3 are insulin independent, while GLUT4 is insulin-sensitive.
How is GLUT4 expression on membrane of muscle and adipose tissue cells regulated by insulin?
Muscle and adipose tissue cells have insulin receptors. Insulin binds to these receptors to stimulate GLUT4 translocation to the membrane (vesicle fuses with the membrane) for uptake of glucose.
Insulin is a ____ hormone, acts in ____ state.
Glucagon is a _____ hormone, acts in ___ state.
Insulin is an anabolic (builder) hormone, acts in feeding/absorptive state to store energy
==> Promotes storage of metabolic fuel via glycogenesis (glucose to glycogen), lipogenesis (FFA to TGL), proteogenesis (AA to protein)
Glucagon is a catabolic (destroyer) hormone, acts in fasting/postabsorptive state to release glucose for body to use as energy
==> Promotes breaking down of energy stores to be used as glucose fuel, processes involve glycogenolysis, lipolysis, proteolysis, gluconeogenesis
What is gluconeogenesis?
Generation of glucose from non-carbohydrate carbon substrates (occurs in liver, like glycogenolysis)
E.g., from aa to glucose, from glycerol to glucose
Describe the autoimmune process of Type 1 diabetes
Pancreas B cells are destroyed and hence no longer make insulin
Type 2 diabetes is also known as non-insulin dependent DM, why?
Pancreas B cells able to produce insulin but not in sufficient amounts OR body does not use it well (insulin resistance)
Insulin resistance: receptor not activated by insulin to open gate for glucose uptake, hence glucose less able to enter cell and supply energy
What are the 6 immediate effects of insulin deficiency?
Glucose
1. Incr hepatic glucose output
2. Dcr glucose uptake by cells
Triglycerides
1. Dcr triglyceride synthesis
2. Incr lipolysis
Proteins
1. Incr protein degradation (proteolysis)
2. Dcr AA uptake by cells
Acute consequences of DM resemble symptoms of exaggerated postabsorptive/fasting state since there is inadequate insulin action.
What are the 3Ps, 1R related to dcr glucose uptake by cells and incr hepatic glucose output?
- Polyuria
- Excess urine production occurs because of excess glucose in blood causing urine in glucose. Osmotic diuresis causes water to be pulled into the urine.
*recall: glucose is 100% reabsorbed in proximal tubule by SGLT2, but SGLT2 can be saturated at max transport rate Tmax. - Polydipsia
- Extreme thirst results from dehydration due to polyuria - Polyphagia
- Excessive eating, incr in appetite occurs due to intracellular glucose deficiency - Renal failure
- Dehydration causes dcr blood volume, peripheral circulatory failure, and eventually renal failure
