Endocrine cells of the pancreas Flashcards
What do b cells secrete?
insulin and C peptide
What do alpha cells secrete?
Glucagon
What do delta cell secrete?
Somatostatin
What do F cells (PP cells) secrete?
Pancreatic polypeptide
Acts as a satiety signal
How does blood flow in the islets?
From center to periphery
How is insulin formed?
Preproinsulin –> proinsulin –> insulin and C peptide
Proinsulin still has C peptide attached
Proinsulin is packaged into secretory granules and then cleaved
What are the steps of insulin release?
Glucose enters cell via GLUT-2
Glucose is phyosphrylated by glucokinase
Glucose-6-phosphate is oxidized promoting ATP generation
ATP closes the “inward rectifying” K+ channels
Plasma membrane is depolarized and Ca2+ channels activate
Ca2+ enters cell and causes insulin and C-peptide to exocytosis
What closes the K+ channels?
ATP
What is the sulfonylurea receptor?
Increases insulin secretion by causing easier depolarization and more ca2+ entry
What are the intracellular steps of glucose uptake through GLUT4?
Insulin binds to receptor
physophorylation of insulin receptor substrate
Substrate proteins phosphorylate and activate/inactivate downstream pathways
Translocation of vesicles containing GLUT4 to membrane
Glucose enters via facilitated diffusion
What do MAP kinase, PI3k, and AKT do?
Increase glycogen/lipid/protein synthesis
decrease lipolysis
cell growth and differentiation
What does activation of AMP-kinase result in?
GLUT4 translocation to plasma membrane
this is indepedent of insulin
What are stimulatory factors of insulin secretion?
Increased glucose, AA, FA, and ketoacid concentration
Glucagon
Cortisol
GIP
K+
Vagal Stimulation, Ach
Sulfonylurea drugs
What are inhibitory factors of insulin secretion?
Decreased blood glucose
Fasting
Exercise
Somatostatin
alpha-adrenergic agonists; norepinephrine
Diazoxide (K+ channel activator, relaxes smooth muscle)-used to treat hypoglycemia
How does insulin affect skeletal muscle?
Increased glucose uptake
Increased glycogen synthesis
Incrased glycolysis and CHO oxidation
Increased protein synthesis
Decreased protein breakdown
How does insulin affect the liver?
Increases glycolysis and CHO oxidation
Decrease gluconeogensis
Increase pyruvate oxidation
Increase lipid storage and decrease lipid oxidation
How does insulin affect adipose tissue?
Increased glucose uptake
Increased glycolysis
Decreased lipolysis
Promotes uptake of fatty acids
How does insulin affect blood levels of certain substances?
The effect on blood level is the opposite of the action of insulin
Ex. Insulin increases protein synthesis so there are decreased AA in the blood
Where is glucagon stored?
In dense granules of Alpha-cells
What stimulates the secretion of glucagon?
Decreased blood glucose
Increased AA (arginine & alanine)
Fasting
CCK
B-adrenergic agonists
Ach
What inhibits glucagon production and secretion?
Insulin
Somatostatin
FA
Ketoacids
What are the affects of glucagon secretion?
Increased blood glucose
Increased glucoenogensis
Increased glucogenolysis
Inhibits glycogen synthesis
Explain general diabetes for the blood
Insulin resistance –> decreased tissue glucose utilization –> spills over into blood –> hyperglycemia
Explain general diabetes for adipose tissue
Increased lipolysis (free fatty acids) –> Polyphagia
Increased lipolysis–> gluconeogenesis and ketogenesis
Explain diabetes for muscle
Increased protein catabolism (amino acids)
–> gluconeogenesis
Explain general diabetes for liver
Glucagon excess leads to increased gluconeogenesis and Ketogenesis
Explain general diabetes for the kidney
Ketoacidosis and hyperglycemia lead to ketonuria and glycosuria
–> polyuria–>volume depletion–> polydipsia
What is type 1DM?
Destruction of B-cells
Decreased utilization of ketoacids results in diabetic ketoacidosis (DKA)
What are some results of type 1 DM?
Hyperkalemia-shift of K+ out of cells
Increased blood glucose increased filtered load of glucose, exceeds reabsorptive capacity of proximal tubule
What are some drawbacks of Type 1 DM insulin replacement?
Lag between glucose measurement & insulin dosing
delayed absoprtion of insulin following injections
What is type 2 DM?
Exhaustion of active B-cells due to environmental factors
patients produce insulin but often have to produce more and more
What are the results of obesity induced insulin resistance?
Decreased GLUT-4 uptake of glucose in response to insulin
Decreased ability of insulin to repress hepatic glucose production
Inability of insulin to repress adipose tissue uptake (LPL) and lipolysis (HSL)
How else can Type 2 diabetes occur in non-obese patients?
Due to decreased insulin release by pancreas indepedent of peripheral insulin resistance
What are incretin hormones and what do they do?
Hormones in the intestinne that are secreted in response to GI glucose and fat
Stimulates insulin secretion
Inhibits glucagon secretion
Slows gastric emptying
What are some associated conditions of type 1 DM?
Autoimmune thyroid disease
celiac disease
addison’s disease
What are some associated conditions to type 2 DM?
Obesity
lipid abnormalities
