test 7 Flashcards
Major pancreatic hormones
- insulin and glucagon
* Secretion determined by plasma substrate levels
What do insulin and glucagon do
• They coordinate disposition of nutrients from meals and the flow of endogenous substrates during fasting via actions on liver, adipose tissue, and muscle.
Insulin
• The hormone of “abundance”. When nutrients are in excess, insulin stores the excess as fuel.
Glucagon
• The hormone of “starvation” and promotes the mobilization these fuels when nutrient supply is low.
endocrine cells of the pancreas
- The endocrine cells of the pancreas are arranged in clusters, called the ISLETS, which compose of 1-2% of the pancreatic mass
- Each cell contain 4 cell types
- The intimate contact of the cell types indicate a paracrine function; one cell type can alter the function or secretion of another nearby or adjacent cell type.
Alpha cells secrete
- glucose
- 20% of islets cells
Beta cells secrete
- insulin
- 65% of islets cells
Delta cells secrete
- somatostatin
- 10% of islets cells
F cells secrete
- pancreatic polypeptide
- 5% of islets cells
Stimulants (secretagogues) of insulin release include:
- glucose
- amino acids (leucine, arginine)
- glucagon-like polypeptide (GLP-1)
- glucose-dependent insulinotropic polypeptide (GIP)
- glucagon
- cholecystokinin
- vagal activity
Mechanism of insulin secretion by glucose
Uptake of glucose into the Beta cell by a “glucose sensor”, GLUT2.
Metabolism of glucose produces ATP.
ATP closes the ATP-sensitive K+ channels, which depolarizes the -cell membrane.
This opens the Ca2+ channels, allowing Ca2+ to flow inside, increasing [Ca2+]i.
Increased Ca2+ causes exocytosis of insulin-containing granules.
Disposal of glucose by insulin in peripheral tissues
Insulin binds to an insulin receptor located in tissues; liver, muscle, adipose tissue.
The insulin receptor is activated, and proteins of the insulin-receptor substrate (IRS) family are phosphorylated.
The IRSs activate other kinases within the cell, which translates the insulin signal to metabolic effects; glucose and K+ uptake, glycogen synthesis, lipogenesis, cell growth.
When your levels of sugar (glucose) go over your normal (>110 mg/dl)
- Insulin is released (Beta cells are activated):
- activates glucose uptake
- increases the use of glucose and ATP generation
- converts glucose to glyocgen
- increases amino acid absorption and protein synthesis
- increases triglyceride synthesis (increases adipose tissue mass) - all of this ultimately results in a decrease in glucose (blood sugar)
When your levels of sugar (glucose) go below your normal (<70 mg/dl)
- glucagon is released (from Alpha cells)
- increased breakdown of glycogen to glucose (in the liver and skeletal muscles)
- increased breakdown of fats to fatty acids (adipose tissue)
- increased synthesis and release of glucose (liver)
Incretin (coming from the gut) effect
- the existence of gut-derived factors or hormones that enhance glucose-stimulated insulin secretion by the pancreatic β-cell
- Insulin secretion elicited by oral glucose is greater than following intravenous delivery.
- The incretins are glucose dependent insulinotropic peptide (GIP), and glucagon like peptide (GLP-1).
As the food passes through the GI tract, what is being released and activated in the circulation
- glucose dependent insulinotropic peptide (GIP), and glucagon like peptide (GLP-1).
glucose dependent insulinotropic peptide (GIP), and glucagon like peptide (GLP-1) target what and cause
- targets the Beta cell in the pancreas
- causes an increase in insulin production => increasing cellular glucose uptake
glucagon like peptide (GLP-1) targets what and cause
- targets Alpha cells in the pancreas
- suppresses glucagon release
- which targets the liver
- decrease production of glucose => decrease in hepatic glucose output
glucose dependent insulinotropic peptide (GIP), and glucagon like peptide (GLP-1) metabolized very quickly in the plasma by
- enzyme known as Dipeptidyl peptidase (DPP)
Diabetes
- metabolic condition where blood sugar levels are extremely high
Classification of diabetes: 4 classes
Type 1 Type 2 Type 3 ? (Associated with Alzheimer’s Disease) Gestational Other
Type 1
- pancreas failure
- causes blood sugar to rise
• Commonly affects children, adolescents, or young adults.
• Characterized by insulin deficiency due to destruction of β-cells.
• Loss of function results from autoimmune processes. Presence of islet cell antibodies or autoantibodies to insulin.
• Pancreas fails to produce insulin and respond to glucose, and patients show classic symptoms of insulin deficiency (polydipsia (excessive thirst), polyphagia (excessive hunger), polyuria (sugar in urine), and weight loss).
• Treatment requires exogenous INSULIN to control glucose and prevent ketoacidosis.
Type 2
- Type 2 diabetes accounts for greater than 90% of cases.
- Etiology is unknown, but is influenced by genetic factors, obesity, ageing, physical inactivity.
- Type 2 ranges from insulin resistance (hyperinsulinemia) to insulin secretory defect with peripheral insulin resistance. Pancreas retains some β-cell function, but insulin secretion is inadequate.
- Blunted/decreased phase 1 and 2 insulin secretion.
Insulin resistance
- Resistance is a lack of sensitivity of target organs to insulin.
- Weight loss, exercise, and diet modification decrease insulin resistance and improve glycemic control in some patients.
- However, most require some form of pharmacological intervention.
