Insulin & Glucagon Flashcards
What occurs during the anabolic phase of homeostasis? What is this phase also known as?
Synthesis of compounds constituting the body’s structure (e.g. protein and glycogen synthesis)
AKA: Fed state
What is the relationship between caloric intake and demand during the anabolic phase? Is energy stored or mobilized?
Caloric intake > demand
energy storage
What occurs during the catabolic phase of homeostasis? When does it occur?
Oxidative processes that release energy (e.g. Ox phos and ETC)
4-6 hours after food ingesting; lasts until person eats again
What is the relationship between caloric intake and demand during the catabolic phase? Is energy stored or mobilized?
Caloric intake < demand
energy mobilization
What are the endocrine and exocrine products of the pancreas?
Endocrine: insulin, glucagon, somatostatin
Exocrine: digestive enzymes and HCO3-
What are endocrine sections of the pancreas called?
Islets of Langerhans
Label the cell types of an islet of Langerhans
What do α cells secrete?
Glucagon
What do β cells secrete?
Insulin
What do δ cells secrete?
Somatostatin
What are the functions of the A & B chains of insulin?
A: species-specific sites
B: biological activity
Where is the C-peptide cleaved from the A and B chains of insulin?
Golgi
What is the half-life of insulin? How is it cleared from the body?
4-6 minutes
cleared by receptor-mediated endocytosis and lysosomal insulinases
Why do diabetics have to administer themselves more insulin than is needed for metabolism?
~50% of insulin in a single pass through the liver
What kind of receptors are insulin receptors? How do they function when insulin binds?
Tyrosine kinase-containing receptors
Dimerizes and triggers autophosphorylation of β subunits; phosphorylates cytoplasmic insulin receptor substrate (IRS-1 & IRS-2)
What would cause a downregulation of insulin receptors (3)?
Obesity
High carbohydrate intake
Insulin resistance
What would cause an upregulation of insulin receptors (1)?
Fasting
What are the two signal transduction pathways that insulin activates? What do they stimulate?
Mitogen-activated protein (MAP) kinase pathway: promotes cell growth and DNA synthesis
Phosphatidylinositol-3-kinase pathway: inserts GLUT4 to membranes of skeletal muscle and adipose tissue; stimulates glycogen, lipid, and protein synthesis
How much insulin does an average adult pancreas secrete?
~40-50 units/day
What is a normal basal level of insulin secreted daily?
10 μU/mL (50% of total daily insulin)
What does “bolus insulin” refer to?
Insulin secreted outside of the basal level
Secretion of insulin is biphasic. How do insulin levels change during each phase?
Early phase: initial burst of insulin in the first 10 minutes after a meal; fusion of docked granules
Late phase: slower rise of insulin release; mobilization from a reserve pool
What amino acids can stimulate insulin secretion (3)?
Alanine
Lysine
Arginine
What is the function of incretins? Where are they secreted from? Example?
Amplify glucose-induced insulin release
Secreted from intestines
Ex: gastric inhibitory peptide & GLP-1
Does acetylcholine stimulate or inhibit insulin secretion?
Stimulate
Does Epi or NE have a greater inhibitory effect on insulin secretion?
Epi
What is the difference between SGLT and GLUT transporters?
SGLTs are coupled to sodium and GLUTs are not
How many glucose transporters are encoded in the human genome?
14
Where are SGLT1 transporters located?
Intestinal and renal epithelium
Where are SGLT2 transporters located?
Renal epithelium
Where are GLUT1 and GLUT3 transporters located? Under what conditions are they active?
Located everywhere
Always on
Where are GLUT2 transporters located? When are they active?
Located on pancreatic β cells and hepatic cells
Only active at high [glucose]; bidirectional transport
Where are GLUT4 transporters located? When are they activated?
Located on skeletal muscle, heart, and adipose tissue
Activated when insulin binds to its receptor
Where are GLUT5 transporters located? What do they transport?
Located on the brush border of small intestinal cells (enterocytes)
Transport fructose
Explain the cascade of events that occur in a pancreatic β cell that leads to secretion of insulin (4).
- Glucose enters through GLUT2 and generates ATP
- ATP-sensitive K+ channel closes (coupled to sulphonylurea receptor)
- Trapped K+ depolarizes membrane and Ca2+ influxes
- Insulin secreted
Why can administration of sulphonylureas lead to hypoglycemia?
Triggers insulin secretion independent of glucose
Inhibits ATP-sensitive K+ channel, leading to depolarization
Skeletal muscle, adipose tissue, and the heart are responsible for ___% of the body’s glucose metabolism. Of the three ______ takes up 80%
40%
Skeletal muscle
What happens to GLUT4 transporters when insulin binds to its receptor?
Upregulation of GLUT4
New transporters added to the cell membrane from the Golgi
What are the two triggers for diabetic ketoacidosis?
Lack of insulin
Increased counterregulatory hormones due to stress
How much insulin is necessary to inhibit lipolysis and the generation of ketone bodies?
1-2 μU/mL
How much insulin is necessary to affect glucose metabolism in the liver and muscle?
25-50 μU/mL
How much insulin is necessary to stimulate glucose uptake into fat?
10 μU/mL
How is hyposecretion (diabetes mellitus) characterized (2)?
Abolsute relative deficiency of insulin
Absolute relative excess of glucagon
What are the major characteristics of hyperglycemia (3)?
Polyuria
Polydipsia
Polyphagia
Why does hyperglycemia cause polyuria?
Excess glucose is greater than glucose renal tubular maximum, which acts as an osmotic diuretic
Why does hyperglycemia cause polydipsia?
Dehydration occurs due to osmotic diuresis
Why does hyperglycemia cause polyphagia?
Insulin inhibits feeding, so lack of insulin could increase appetite
Intracellular glucose is low, which signals starvation
To be diagnosed with diabetes, someone must meet one of four criteria. What are they?
Diabetes symptoms w/ blood glucose of 200 mg/dL
Fasting blood glucose ≥ 126 mg/dL
2-hour oral glucose tolerance test ≥ 200 mg/dL
Hemoglobin A1c ≥ 6.5%
What fasting blood glucose is considered pre-diabetic?
100-125 mg/dL
How many people in the US have diabetes and how many are pre-diabetic?
34.2 million with diabetes
88 million pre-diabetic
What ethnic groups have the highest rates of diabetes?
Pacific Islanders and Native Americans
What viruses cause someone to develop type 1 diabetes? (3)
Coxsackie B4
Mumps
Rubella
Antibodies to what three antigens can lead to type 1 diabetes?
Insulin
Glutamic acid decarboxylase
Islet antigen-2
What are the symptoms of diabetic ketoacidosis? Does it occur more commonly in type 1 or type 2 diabetes?
Type 1
abdominal pain
nausea
vomiting
Are sulfonylureas used to treat type 1 or type 2 diabetes? Explain.
Type 2
Sulfonylureas trigger insulin secretion, even in the absence of glucose. Type 1 diabetics cannot produce insulin, so sulfonylureas would not work.
What are four challenges that increase the risk of type 2 diabetes?
Decreased AMP-kinase (AMPk) activity
Increased persistent organic pollutants (POPs)
“Thrifty” genotypes
Increased cortisol
What is the function of AMP-kinase?
“Metabolic switch”; switches between ATP-consuming processes (ie. GNEO) and ATP-generating processes (ie. lipid oxidation)
What two inflammatory proteins are released from adipose tissue in response to them becoming overfat (“angry fat”). What process do they interfere with?
Tumor necrosis factor (TNF-α)
IL-6 (from macrophages)
Interfere with insulin-receptor signaling, ultimately leading to type 2 diabetes
Based on the graph of the oral glucose tolerance test, which line represents someone with diabetes mellitus?
What is the function of metformin?
Insulin sensitizer
What is the key way to prevent diabetes?
Weight loss
What are some long-term complications of type 2 diabetes (6)?
Coronary artery disease
Cerebrovascular disease
Peripheral vascular disease
Retinopathy
Nephropathy
Neuropathy
What is the “albatross around your neck” when it comes to treating diabetes? Why?
Hypoglycemia
Imbalance between diabetes meds and food intake/activity
Hypoglycemia leads to more hypoglycemia
What are the counterregulatory hormones to insulin (5)? Which has the greatest effect (*).
Growth Hormone
Cortisol
Epinephrine
Norepinephrine
*Glucagon
What are the three major functions of glucagon?
**Mobilization of glucose (glycogenolysis and GNEO)
Lipolysis
Ketogenesis
What is the insulin/glucagon (I/G) ratio in the fed state vs fasting state?
Fed I/G: 30
Fasting I/G: 2
What are the major and minor regulators of glucagon secretion (6)?
Major:
Hypoglycemia
Minor:
Dietary amino acids
Epinephrine
SNS
Cortisol
Growth hormone
What is GLP-1?
Glucagon-like peptide-1
In the intestines, alternative processing of proglucagon –> GLP-1
What are the signs and symptoms of a glucagonoma (5)?
5 D’s
Depression
Diabetes
Declining weight
Deep vein thrombosis
Dermatitis
What are the short term and long term treatments for a glucagonoma (2)?
Short term: somatostatin analogs (ie. octreotide)
Long term: surgery
