Week 4 Hormones Affecting Glucose Metabolism Module

Question 1

T2DM is characterized by…

Answer 1

hyperglycemia

Question 2

what is the underlying pathophysiology of T2DM (5)

Answer 2

peripheral insulin resistance, progressive B-cell dysfunction, hypersecretion of glucagon, accelerated gastric emptying (increased postprandial glucose levels), impaired incretin effect

Question 3

what is the role of incretins? where are they located?

Answer 3

gut peptides that stimulate insulin secretion following oral nutrient ingestion or postprandially. A large proportion of the insulin response in healthy individuals in incretin-mediated (IV glucose infusions do not create the same amount of insulin as equivalent oral glucose intake)

Question 4

following a meal compare insulin and glucagon level in a normal and T2DM individual

Answer 4

Normal: insulin levels rise, glucagon levels

T2DM: delayed and suppressed insulin response, glucagon over-secretion

Question 5

what are the two major type of incretins in humans?

Answer 5

GLP-1 and GIP

Question 6

GLP-1 secreted by? location?

Answer 6

Gut-L cells (eneteroendocrine cells) located in distal ileum and colon. (GLP-1 is derived form the transcription product of proglucagon gene)

Question 7

describe GLP-1 release into circulation

Answer 7

Biphasic: release shortle after food ingestion and then another as food interacts with L-cells in ileum and colon

Question 8

what is the role of GLP-1 on the pancreas 2

Answer 8

potentiates insulin release from B cells, inhibits glucagon secretion

Question 9

what is the role of GLP-1 outside of the pancreas 4, and one long-term

Answer 9

inhibits gastric emptying (slows rate of nutrient absorption and slows rate of glucose appearing in the blood)

reduces appetite,

enhances insulin sensitivity of peripheral tissues (skeletal muscle)

cardioproteciton and neuroprotection

long term: increase B-cell mass

Question 10

GIP; where is it produced, by what cell type?

Answer 10

produced in duodenum and jejunum by K cells

Question 11

GLP-1 and GIP are secreted in response to….and are degraded within minutes by

Answer 11

ingestion of food, dipeptidyl peptidase-4 (DPP4)

Question 12

contrast role of GLP-1 and GIP

Answer 12

both stimulate insulin secretion and expand B cell mass. Only GLP-1 suppresses glucagon, inhibits gastric emptying, and decreases food intake

Question 13

compare GLP-1 and GIP secretion in T2DM

Answer 13

GLP-1 level is decreased, GIP levels typically not decreased

Question 14

is GLP-1 replacement effective in reducing Fasting Plasma Glucose in T2DM?

Answer 14

Yes! increases insulin, decreased glucagon

Question 15

is GIP replacement in reducing FPG in T2DM?

Answer 15

no, GIP levels are normal in T2DM yet functionally ineffective in stimulating insulin secretion

Question 16

what is one obstacle in using GLP-1 as a therapy? what are 2 potential solutions?

Answer 16

it is degraded relatively quickly by DPP-4 located in human serum. Solution: create a GLP-1 mimic that can bind pancreas but not be degraded by DPP-4, or by inhibiting DPP-4

Question 17

what is Exenatide (Byetta), method of taking?

Answer 17

GLP-1 receptor agonist, mimics the effects of GLP-1 (twice daily injection treatment)

Question 18

what is Liraglutide? method of taking?

Answer 18

modified synthetic peptide form human GLP-1 w/ a half life of 10-14hrs (once daily injection treatment)

Question 19

What is DPP4i (vildaglipton and Sdaglipitn)? method of taking?

Answer 19

inhibitor of DPP-4 (prevent GLP-1 degradaiton), once daily ingestion

Question 20

what are some pros/cons of DPP4 inhibitors and incretin mimitics?

Answer 20

DPP4I: ingestible (Pro), weight neutral (Pro)

GIP-1 analogs: SQ injected (con), increase risk of thyroid cancer (con), weight loss (pro)

Question 21

what are counterregulatory hormones (CRH)?

Answer 21

CRH are hormones that work against action of insulin

Question 22

ex of CRH 4? fast acting or slow

Answer 22

Glucagon (fast), Epinephrine (fast), cortisol (slow), growth hormone (slow)

Question 23

elevations in CRH cause (5)

Answer 23

hepatic ketogenesis, increased lipolysis in adipose, increased proteolysis in muscle, increased glycogenolysis, increased gluconeogenesis

Question 24

what is our bodies normal defense against hypoglycemia? (5)

Answer 24

insulin decrease, glucagon incresases, epinephrine increases, cortisol and growth hormones incease

Question 25

defective defense against hypoglycemia is seen in…

Answer 25

T1DM

Question 26

describe the impaired CRH response in hypoglycemia

Answer 26

glucagon response is lost and Epinephrine becomes main CRH against hypoglycemia. However, Epi response decreases after recurring hypoglycemia

Question 27

What is hypoglycemia-associated autonomic failure

Answer 27

hypoglycemia induces further hypoglycemia by blunting the effects of epinephrine

Question 28

what is diabetic ketoacidosis (DKA)? characterized by?

Answer 28

complication of diabetes where the body produces excess blood acids.

Characterized by hyperglycemia and ketonemia

Question 29

what is the mechanism of DKA?

Answer 29

1. Glucose is not utilized by the body (insuficient or absent insulin)
2. The body begins to break down fat (for energy) resulting in ketone by-products that accumulate in the blood
3. the accumulation of ketone and glucose are removed by the kidneys, but require more water do so
4. water and excess glucose and ketones are lost but loss of water worsens ketoacidosis

Question 30

what are symptoms of DKA (4)

Answer 30

nausea/vomiting
thirst (polyuria)
abdominal pain
shortness of breath

Question 31

physical findings of DKA (5)

Answer 31

tachycardia, dehydration/hypotension, respiratory distress, abdominal tenderness, possibly coma

Question 32

DKA is characteristic of ____ but a _____ can trigger it in _____

Answer 32

T1DM, severe illness, T2DM

Question 33

what is hypoglycemia unawareness?

Answer 33

the fact that brain cells have a greater glucose uptake than other tissues leads to hypoglycemia unawareness

Question 34

What would you expect so see in a T1DM patient who is suffering from his first hypoglycemia

Answer 34

suppressed glucagon and elevated epinephrine. For T1DM>5yrs, their glucagon response to hypoglycemia is lost and Epinephrine constitutes the main defense against hypoglycemia