2-5-16-Endocrine Pancreas (Lopez) Flashcards
___ permits rapid cell-to-cell communication between alpha cells, beta cells, and alpha to beta cells
Gap junctions
___ blood from the beta cells carries insulin to the alpha and delta cells
Venous
Insulin is a ____ hormone made of 2 straight chains linked by disulfide bridges
Peptide
___ has 4 peptides (signal peptide, A and B chains of insulin, and a connecting peptide (C peptide))
Preproinsulin
___ does not have a signal peptide, the C peptide is still attached to insulin, disulfide bridges form in the ER (folded form of insulin), packaged in secretory vesicles in the golgi, and proteases cleave this during packaging
Proinsulin
___ is used to test beta cell function in T1D patients receiving insulin injections
C peptide
___ drugs promote the closing of ATP-dependent K+ channels and leads to increased insulin secretion. It can be used in the treatment of type 2 diabetes
Sulfonylurea, i.e., tolbutamide and glyburide
Glucose stimulates insulin secretion in a ____ manner
Biphasic
See slide 11 for graph
Insulin facilitates glucose uptake in some tissues by inserting this transporter ___ and insulin is required for glucose uptake in ___ tissues
GLUT 4
Adipose, resting skeletal muscle, and liver
What are the major effects of insulin in skeletal muscle?
- Increase glucose uptake –> increases GLUT4 transporter
- Increase glycogen synthesis –> increase hexokinase (glucokinase in liver) and activate glycogen synthase
- Increase glycolysis and Carb oxidation –> increase hexokinase, PFKase, and pyruvate DHase
- Decrease gluconeogenesis
- Increase protein synthesis and decreas protein breakdown
What effect does insulin have on triglyceride uptake in adipose tissue?
Insulin has a stimulatory effect on the uptake of TGs via lipoprotein lipase
What effect does insulin have on the uptake of FA’s in adipose tissue?
Stimulatory effect
WHat role does insulin play in the conversion of TG’s to glycerol via hormone sensitive lipase?
Inhibits hormone sensitive lipase
WHat effect does insulin have in the uptake of glucose and conversion to a-Glycerol-P in adipose tissue?
Stimulatory effect
What effect does insulin have on blood levels of the following: A-Glucose B-FA's c-Ketoacids D-AA's
All decreased
What effect does insulin have on the following in the liver?
A-Glucokinase
B-Glycogen synthesis
C-Glucose-6-phosphatase (glucose release/gluconeogenesis)
D-Glycolysis
E-Triglyceride storage and export
F-Protein synthesis
a-Increase B-Increase C-Decrease D-Increase E-Increase F-Increase protein synthesis, decrease protein degradation
What effect does insulin have on the following in adipose tissue?
A-GLUT4 transporters
B-Glycolysis
c-Triglycerides (specifically hormone sensitive lipase and lipoprotein lipase)
A-Increase
B-Increase –> increase alpha-glyercol-phosphate, increase acetyl coa, increase FA synthesis
C-Increase –> decrease HSL, increase LPL
What effect does insulin have on the following in skeletal muscle? A-GLUT4 transporters B-Glycogen synthesis C-Glycolysis D-Protein synthesis and degradation e-Triglycerides
A-Increase B-increase C-increase D-Increase synthesis, decrease degradation E-Increase (FA's from circulation)
What are some inhibitory factors of insulin?
Decrease blood glucose Fasting Exercise Somatostatin Alpha-adrenergic agonists Diazoxide
___ is characterized by inadequate insulin secretion, destruction of beta cells, often as the result of autoimmune disease
Type I DM
Describe the levels of the following in Type I DM:
A-Blood [glucose]
B-Blood [FA] and [ketoacid]
C-[AA]
A-Increase –> decrease glucose uptake, decreased glucose utilization, increased gluconeogenesis
B-Increase –> decreased FA synthesis, decrease TG synthesis, Increased TG breakdown, increased level of circulating Free FA, increase conversion of FA to ketoacids and decreased ketoacid utilization by tissues (results in DKA: metabolic acidosis)
C-Increase –> increase protein breakdown, decreased protein synthesis, increased catabolism of AA (loss of lean body mass), increased ureagenesis
What happens to K+ due to the effects on insulin in type 1 DM??
Hyperkalemia –> shift K+ out of the cell: IC [K+] is low, lack of insulin effect on Na/K ATPase
Even though plasma levels may be above normal, total body K+ is usually below normal due to the polyuria and dehydration
What happens to GLUT4 uptake of glucose in response to insulin release in Type 2 DM?
Decreased
What happens to HSL and LPL in adipose tissue in Type 2 DM?
Inability of insulin to repress HSL or increase LPL in adipose tissue
What are some insulin secretagogue treatment options for type 2 DM?
Sulonylurea drugs and Incretin analog of GLP-1 (exenatide); injection needed
What are some treatment options for the slow absorption of carbohydrates in pts with Type 2 DM?
Alpha-glucosidase inhibitors (acarbose, miglitol)
Amylin analogs (pramlintide)
What are some insulin sensitizers to treat type 2 DM?
Biguanide drugs (metformin): upregulate insulin receptors on target tissues
To obtain [glucose] in mg/dL, multiply the value in mmol/L by ___
18
Glucagon is a member of a family of peptides that includes the GI hormones ____
Secretin and GIP
What are some stimulatory factors of glucagon secretion?
- decreased blood glucose
- increased AAs (arginine and alanine)
- Fasting
- CCK
- B-adrenergic agonists
- Ach
What are inhibitory factors of glucagon?
- Insulin secretion
- Somatostatin
- Increase [FA] and [ketoacid]
What effect does glucagon have on glycogenolysis?
Increases –> inhibits glycogen formation from glucose
What effect does glucagon have on gluconeogenesis?
Increases gluconeogenesis by decreasing the production of fructose 2,6-bisphosphate
What effect does blood glucagon levels have on the following?
A-blood Glucose
b-FAs
C-Ketoacids
All increase
List examples of Incretin hormones
Intestine-derived hormones –> GLP-1, GIP
Have a short 1/2 life and secreted in response to GI glucose and fat
What effect does incretin hormones have on insulin secretion? Glucagon secretion? Gastric emptying?
Simulates insulin secretion
Inhibits glucagon secretion
Slow gastric emptying
___ is ~60-65% of the islet of langerhans, secretes insulin and C peptide, and tends to be located in the peripheral core
___ is ~20% of the islet, secretes glucagon, and tends to be peripherally located
___ is ~5% of the islet and secretes somatostatin. Also have a neuronal appearance and send dendrite-like processes to cells that secrete insulin
Beta cells
Alpha cells
Delta cells–> interspersed between alpha and beta cells
