The Endocrine Pancreas

Question 1

Insulin response to glucose

Answer 1

Biphasic; basic AAs will also stimulate this response

Question 2

Incretin response to ingested glucose

Answer 2

Increased secretion from the GI tract leads to increased secretion of insulin; GLP-1 also suppresses glucagon secretion and is therefore more potent

• Requires glucose to produce strong stimulus
• GLP-1 and GIP are rapidly degraded by DPP4

Question 3

Incretins in T2DM

Answer 3

Same amount produced; however, B-cells are less capable of responding

Question 4

Mechanism of Insulin Secretion

Answer 4

Glucose enters the hepatocyte via GLUT-2 and is broken down by glucokinase producing ATP

=>Increased ATP binds to K+ channels depolarizing the cell and opening Ca2+ channels=>Release of insulin via exocytosis

Question 5

Sulfonylureas

Answer 5

Bind to K+ channels promoting depolarization and the secretion of insulin from hepatocytes

Question 6

Neural control of insulin release

Answer 6

Vagal stimulation => Increased

Exercise and stress => Decreased (via B2-adrenergic receptors)

Question 7

Insulin Receptors

Answer 7

Involves the autophosphorylation of tyrosine kinases and the phosphorylation of IRS docking sites

=>PI-3 activation that leads to the mobilization of GLUT-4 to the plasma membrane

*Also capable of activating the MAP/Kinase pathway which
=>activation of Ras proteins and increasing transcription factors

Question 8

Fate of the insulin hormone-receptor complex

Answer 8

Receptor is internalized, dephosphorylated, and degraded by endosomes

*Chronic exposure of insulin => increased internalization and degradation (down-regulation)

Question 9

Control of Glucagon secretion

Answer 9

Hypoglycemia; low carb/protein ratio in meal

-Mediated in part by stimulation of B-adrenergic receptors

Question 10

Characteristics of GLUT-2

Answer 10

Has a low affinity (high Kt) for glucose; therefore, entry to the hepatocyte is only permitted when glucose concentrations are high

*Much like how glucokinase has a high Km

Question 11

Insulin effects in liver

Answer 11

1. Increased expression of glucokinase
2. Increased expression of glycogen synthase
3. Prevents release of glucose
4. Inhibits gluconeogenesis
   
   • also inhibits protein metabolism peripherally
5. Stimulates FA synthesis

Question 12

Glucose Utilization in skeletal muscle

Answer 12

Is converted to either ATP or non-mobilizing glycogen

*Exercise can also stimulate the mobilization of more GLUT-4 transporters to the plasma membrane

Question 13

Effects of insulin on Adipose

Answer 13

Moves GLUT-4 and activated LPL to the cell membrane to absorb glucose and FAs/glycerol respectively

-Inhibits lipolysis

Question 14

Insulin effects on Ketogenesis

Answer 14

In the liver, insulin will decrease the flow of FAs to the liver and stimulate the formation of malonyl-CoA

-Inhibits the transport of FAs into the mitochondria where they would be oxidized

Question 15

C-peptide

Answer 15

Product produced by the cleavage of insulin in the secretory granules of B-cells; proinsulin can also be produced in small amounts

Question 16

Primary Source of glucose during a fast

Answer 16

The Liver: mostly glycogenolysis, some gluconeogenesis

Kidney: A small fraction of gluconeogenesis will occur in the kidney

Question 17

Glucagon during a fast

Answer 17

(Liver)

1. Increases expression of glucose-6-phosphatase
2. Stimulates glycogenolysis/gluconeogenesis
3. Promotes AA uptake

Question 18

Cortisol during a fast

Answer 18

Promotes peripheral gluconeogenesis

*Glycogen only acts in the liver

Question 19

GH during a fast

Answer 19

Levels will be increased in order to

1. Inhibit glucose uptake in insulin-sensitive tissues
2. Stimulate lipolysis and FA delivery to the liver for ketone production

Question 20

Urea nitrogen during a fast

Answer 20

Increased due to increased breakdown of skeletal muscle proteins

Question 21

Prolonged Fasting

Answer 21

1. Drop in T3 => Drop in BMR
2. Glucagon inhibits malonyl-CoA formation => ketongenesis
3. Glucose, FFA, and insulin levels are stabilized

Question 22

Sympathetic Signs of Hypoglycemia

Answer 22

Epinephrine release attempts to stimulate lipolysis, glycogenolysis, etc., but also causes palpitation, tachycardia, and sweating

Question 23

Signs of neuroglycopenia

Answer 23

Lack of coordination, lack of concentration, dizziness, confusion, possible coma

Question 24

Endocrine Response to Hypoglycemia

Answer 24

Release of GH (inhibits glucose uptake) and ACTH (promotes cortisol release)

Question 25

Classical Diabetes Symptoms

Answer 25

Polyphagia, polyuria, and polydipsia

To diagnose: 1. HA1c > 6.5%

2. Fasting glucose > 126mg/dl
3. Post-prandial glucose > 200mg/dL

Question 26

T1DM

Answer 26

Characterized by an autoimmune response coating B-cells in Ab and leading to their destruction

*Diabetic ketoacidosis is more common w/ this type

Question 27

T2DM

Answer 27

Heterogenous group of diseases in which insulin deficiencies may develop overtime due to overactive B-cells (would then require exogenous insulin as in T1DM)

*Obesity=major risk factor

Question 28

Insulin Resistance in specific tissues

Answer 28

Liver: Increased glucose production when fasting/decreased glycogen production after meal

Skeletal: Decreased uptake of glucose

Adipose: Reduced lipid clearance => Elevated FFAs

Question 29

Serine Phosphorylation

Answer 29

Inhibitory effect on insulin signal

Question 30

Inhibitor 1

Answer 30

Inhibits phosphatase activity causing an increase in glycogenolysis

*Activated by PKA/cAMP from glucagon stimulation

Question 31

Malonyl-CoA

Answer 31

Blocks the activity of carnitine transferase so B-oxidation of FAs cannot occur in the mitochondria

*Formation in liver cells stimulates by Insulin