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S&F IV: Exam One > The Endocrine Pancreas > Flashcards

Flashcards in The Endocrine Pancreas Deck (31):

Insulin response to glucose

Biphasic; basic AAs will also stimulate this response


Incretin response to ingested glucose

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


Incretins in T2DM

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


Mechanism of Insulin Secretion

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



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


Neural control of insulin release

Vagal stimulation => Increased

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


Insulin Receptors

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


Fate of the insulin hormone-receptor complex

Receptor is internalized, dephosphorylated, and degraded by endosomes

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


Control of Glucagon secretion

Hypoglycemia; low carb/protein ratio in meal

-Mediated in part by stimulation of B-adrenergic receptors


Characteristics of GLUT-2

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


Insulin effects in liver

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


Glucose Utilization in skeletal muscle

Is converted to either ATP or non-mobilizing glycogen

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


Effects of insulin on Adipose

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

-Inhibits lipolysis


Insulin effects on Ketogenesis

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



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


Primary Source of glucose during a fast

The Liver: mostly glycogenolysis, some gluconeogenesis

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


Glucagon during a fast


1. Increases expression of glucose-6-phosphatase

2. Stimulates glycogenolysis/gluconeogenesis

3. Promotes AA uptake


Cortisol during a fast

Promotes peripheral gluconeogenesis

*Glycogen only acts in the liver


GH during a fast

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


Urea nitrogen during a fast

Increased due to increased breakdown of skeletal muscle proteins


Prolonged Fasting

1. Drop in T3 => Drop in BMR

2. Glucagon inhibits malonyl-CoA formation => ketongenesis

3. Glucose, FFA, and insulin levels are stabilized


Sympathetic Signs of Hypoglycemia

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


Signs of neuroglycopenia

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


Endocrine Response to Hypoglycemia

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


Classical Diabetes Symptoms

Polyphagia, polyuria, and polydipsia

To diagnose: 1. HA1c > 6.5%

2. Fasting glucose > 126mg/dl

3. Post-prandial glucose > 200mg/dL



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

*Diabetic ketoacidosis is more common w/ this type



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


Insulin Resistance in specific tissues

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

Skeletal: Decreased uptake of glucose

Adipose: Reduced lipid clearance => Elevated FFAs


Serine Phosphorylation

Inhibitory effect on insulin signal


Inhibitor 1

Inhibits phosphatase activity causing an increase in glycogenolysis

*Activated by PKA/cAMP from glucagon stimulation



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

*Formation in liver cells stimulates by Insulin