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Insulin & Glucagon Flashcards

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1
Q

What occurs during the anabolic phase of homeostasis? What is this phase also known as?

A

Synthesis of compounds constituting the body’s structure (e.g. protein and glycogen synthesis)

AKA: Fed state

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2
Q

What is the relationship between caloric intake and demand during the anabolic phase? Is energy stored or mobilized?

A

Caloric intake > demand

energy storage

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3
Q

What occurs during the catabolic phase of homeostasis? When does it occur?

A

Oxidative processes that release energy (e.g. Ox phos and ETC)

4-6 hours after food ingesting; lasts until person eats again

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4
Q

What is the relationship between caloric intake and demand during the catabolic phase? Is energy stored or mobilized?

A

Caloric intake < demand

energy mobilization

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5
Q

What are the endocrine and exocrine products of the pancreas?

A

Endocrine: insulin, glucagon, somatostatin

Exocrine: digestive enzymes and HCO3-

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6
Q

What are endocrine sections of the pancreas called?

A

Islets of Langerhans

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7
Q

Label the cell types of an islet of Langerhans

A
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8
Q

What do α cells secrete?

A

Glucagon

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9
Q

What do β cells secrete?

A

Insulin

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10
Q

What do δ cells secrete?

A

Somatostatin

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11
Q

What are the functions of the A & B chains of insulin?

A

A: species-specific sites

B: biological activity

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12
Q

Where is the C-peptide cleaved from the A and B chains of insulin?

A

Golgi

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13
Q

What is the half-life of insulin? How is it cleared from the body?

A

4-6 minutes

cleared by receptor-mediated endocytosis and lysosomal insulinases

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14
Q

Why do diabetics have to administer themselves more insulin than is needed for metabolism?

A

~50% of insulin in a single pass through the liver

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15
Q

What kind of receptors are insulin receptors? How do they function when insulin binds?

A

Tyrosine kinase-containing receptors

Dimerizes and triggers autophosphorylation of β subunits; phosphorylates cytoplasmic insulin receptor substrate (IRS-1 & IRS-2)

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16
Q

What would cause a downregulation of insulin receptors (3)?

A

Obesity

High carbohydrate intake

Insulin resistance

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17
Q

What would cause an upregulation of insulin receptors (1)?

A

Fasting

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18
Q

What are the two signal transduction pathways that insulin activates? What do they stimulate?

A

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

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19
Q

How much insulin does an average adult pancreas secrete?

A

~40-50 units/day

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20
Q

What is a normal basal level of insulin secreted daily?

A

10 μU/mL (50% of total daily insulin)

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21
Q

What does “bolus insulin” refer to?

A

Insulin secreted outside of the basal level

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22
Q

Secretion of insulin is biphasic. How do insulin levels change during each phase?

A

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

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23
Q

What amino acids can stimulate insulin secretion (3)?

A

Alanine

Lysine

Arginine

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24
Q

What is the function of incretins? Where are they secreted from? Example?

A

Amplify glucose-induced insulin release

Secreted from intestines

Ex: gastric inhibitory peptide & GLP-1

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25
Does acetylcholine stimulate or inhibit insulin secretion?
Stimulate
26
Does Epi or NE have a greater inhibitory effect on insulin secretion?
Epi
27
What is the difference between SGLT and GLUT transporters?
SGLTs are coupled to sodium and GLUTs are not
28
How many glucose transporters are encoded in the human genome?
14
29
Where are SGLT1 transporters located?
Intestinal and renal epithelium
30
Where are SGLT2 transporters located?
Renal epithelium
31
Where are GLUT1 and GLUT3 transporters located? Under what conditions are they active?
Located everywhere Always on
32
Where are GLUT2 transporters located? When are they active?
Located on pancreatic β cells and hepatic cells Only active at high [glucose]; bidirectional transport
33
Where are GLUT4 transporters located? When are they activated?
Located on skeletal muscle, heart, and adipose tissue Activated when insulin binds to its receptor
34
Where are GLUT5 transporters located? What do they transport?
Located on the brush border of small intestinal cells (enterocytes) Transport fructose
35
Explain the cascade of events that occur in a pancreatic β cell that leads to secretion of insulin (4).
1. Glucose enters through GLUT2 and generates ATP 2. ATP-sensitive K+ channel closes (coupled to sulphonylurea receptor) 3. Trapped K+ depolarizes membrane and Ca2+ influxes 4. Insulin secreted
36
Why can administration of sulphonylureas lead to hypoglycemia?
Triggers insulin secretion independent of glucose Inhibits ATP-sensitive K+ channel, leading to depolarization
37
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
38
What happens to GLUT4 transporters when insulin binds to its receptor?
Upregulation of GLUT4 New transporters added to the cell membrane from the Golgi
39
What are the two triggers for diabetic ketoacidosis?
Lack of insulin Increased counterregulatory hormones due to stress
40
How much insulin is necessary to inhibit lipolysis and the generation of ketone bodies?
1-2 μU/mL
41
How much insulin is necessary to affect glucose metabolism in the liver and muscle?
25-50 μU/mL
42
How much insulin is necessary to stimulate glucose uptake into fat?
10 μU/mL
43
How is hyposecretion (diabetes mellitus) characterized (2)?
Abolsute relative deficiency of insulin Absolute relative excess of glucagon
44
What are the major characteristics of hyperglycemia (3)?
Polyuria Polydipsia Polyphagia
45
Why does hyperglycemia cause polyuria?
Excess glucose is greater than glucose renal tubular maximum, which acts as an osmotic diuretic
46
Why does hyperglycemia cause polydipsia?
Dehydration occurs due to osmotic diuresis
47
Why does hyperglycemia cause polyphagia?
Insulin inhibits feeding, so lack of insulin could increase appetite Intracellular glucose is low, which signals starvation
48
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%**
49
What fasting blood glucose is considered pre-diabetic?
100-125 mg/dL
50
How many people in the US have diabetes and how many are pre-diabetic?
34.2 million with diabetes 88 million pre-diabetic
51
What ethnic groups have the highest rates of diabetes?
Pacific Islanders and Native Americans
52
What viruses cause someone to develop type 1 diabetes? (3)
Coxsackie B4 Mumps Rubella
53
Antibodies to what three antigens can lead to type 1 diabetes?
Insulin Glutamic acid decarboxylase Islet antigen-2
54
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
55
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.
56
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
57
What is the function of AMP-kinase?
"Metabolic switch"; switches between ATP-consuming processes (ie. GNEO) and ATP-generating processes (ie. lipid oxidation)
58
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
59
Based on the graph of the oral glucose tolerance test, which line represents someone with diabetes mellitus?
60
What is the function of metformin?
Insulin sensitizer
61
What is the key way to prevent diabetes?
Weight loss
62
What are some long-term complications of type 2 diabetes (6)?
Coronary artery disease Cerebrovascular disease Peripheral vascular disease Retinopathy Nephropathy Neuropathy
63
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
64
What are the counterregulatory hormones to insulin (5)? Which has the greatest effect (\*).
Growth Hormone Cortisol Epinephrine Norepinephrine \*Glucagon
65
What are the three major functions of glucagon?
\*\*Mobilization of glucose (glycogenolysis and GNEO) Lipolysis Ketogenesis
66
What is the insulin/glucagon (I/G) ratio in the fed state vs fasting state?
Fed I/G: 30 Fasting I/G: 2
67
What are the major and minor regulators of glucagon secretion (6)?
_Major:_ Hypoglycemia _Minor_: Dietary amino acids Epinephrine SNS Cortisol Growth hormone
68
What is GLP-1?
**Glucagon-like peptide-1** In the intestines, alternative processing of proglucagon --\> GLP-1
69
What are the signs and symptoms of a glucagonoma (5)?
**5 D's** Depression Diabetes Declining weight Deep vein thrombosis Dermatitis
70
What are the short term and long term treatments for a glucagonoma (2)?
Short term: somatostatin analogs (ie. octreotide) Long term: surgery

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