Endocrine Pancreas/DM Flashcards by Kolbie Chancellor

Where are a majority of the Pancreatic Endocrine Islets of Langerhans?

Neck

Tail

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Alpha cells release?

Glucagon

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Beta cells release?

Insulin

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Delta cells release?

Somatostatin

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PP cells release?

Pancreatic Polypeptide

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D1 cells release?

VIP

vasoactive intestinal polypeptide

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If there is low glucose, describe what occurs?

Alpha cells release Glucagon to the liver

- Liver breaks down glycogen to release Glucose

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If there is high glucose, describe what occurs?

Beta cells release Insulin

- Liver and Peripheral tissues uptake the glucose which lowers blood levels

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Describe how insulin is released from beta cells in response to glucose elevation

Glucose enters beta cell through GLUT-2
Glucose is metabolized to form ATP
ATP blocks channel that allows K+ out of the cell so it accumulates
Cell Depolarization
Calcium enters the cell
Insulin leaves the cell

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Describe how insulin is released from the beta cell in response to glucose elevation

Glucose enters beta cell through GLUT-2
Glucose is metabolized to form ATP
ATP blocks channel that allows K+ out of the cell so it accumulates
Cell Depolarization
Calcium enters the cell
Insulin leaves the cell

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How is insulin formed?

Proinsulin is cleaved into:

Insulin
C-peptide

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What is C-peptide used for?

Marker of ENDOGENOUS insulin

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Insulin lowers blood sugar, but what are its main effects on peripheral tissues?

Increase glucose uptake into cells for energy
Protein/Glycogen synthesis
Lipogenesis

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Oral glucose causes the release of?

Incretins

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What are 2 Incretins and what causes them to be released/activated?

GLP-1
GIP
– Oral glucose causes their activation/release

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What is the job of Incretins? (GLP-1, GIP)

Stimulate insulin release and (-) Glucagon release

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What can (-) the release of Incretins?

DPP-4

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If DPP-4 (-) the release of Incretins, what then occurs?

(-) release of insulin and (+) release of glucagon => glucose elevation
– INCRETINS DO THE OPPOSITE

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Diabetes Mellitus is impaired glucose homeostasis. What in general, is it due to?

Defective Insulin secretion

Defective Insulin effect (resistance)

What are the levels of A1C, FPG, OGTT and RPG tests that diagnose Diabetes?

A1C: > 6.5%
FPG: > 126
OGTT and RPG: > 200

What causes Type 1 DM?

Autoimmune disease due to failure of T Lymphocyte self tolerance
–> T cells attack antigens on Beta cells!

Once over ____ of beta cells are destroyed with Type 1 DM, there will be symptoms.

> 90%

When does Type 1 DM usually onset and what genetic link does it have?

Onset: childhood/adolescence
Genetic link: MHC class II genes (HLA-DR/DQ on chr. 6)

What marker will be (+) with Type 1 DM?

Islet Autoantibodies

What will be seen on histo with Type 1 DM? (3)

Insulitis: - T cells and Macrophages infiltrate - Low level of beta cells - Islet Atrophy

If you have Insulitis, with t cells and macrophages infiltrating the pancreas and islet atrophy, what type of DM do you have?

Type 1

Describe the stages of Type 1 DM

Stage 1 = autoantibodies are formed Stage 2 = Beta cells are being attacked, there is dysglycemia present Stage 3 = SYMPTOMS

What is the triad of symptoms seen in a child with Type 1 DM?

Polyphagia but thin Polydipsia Polyuria

What is the triad of symptoms seen in a child with Type 1 DM?

Polyphagia but thin because glucose cannot enter cells Polydipsia Polyuria

What causes Type 2 DM? (2)

Insulin resistance in peripheral tissues | Beta cell Dysfunction

When does Type 2 DM usually onset and what is a major risk factor?

Onset: adulthood Risk: OBESITY

What will be seen on histo with Type 2 DM?

Amyloid | -- mild decrease in beta cells too

How does obesity lead to the pathogenesis of Type 2 DM?

- Elevated Adipokines, FFA and inflammation | - These molecules disrupt signals that enable insulin uptake and cause beta cell dysfunction/damage

Once Adipokines, FFA, and inflammation disrupt signals that enable insulin uptake to occur, insulin resistance occurs. Describe what occurs with the beta cells

First: Compensate by secreting more insulin Later: beta cells fail completely and stop secreting insulin

Type 2 DM will manifest symptoms when what occurs?

Beta cell Dysfunction/Failure

What are some general symptoms of Type 2 DM?

Fatigue | Vision changes

MODY

Mature onset of Diabetes in the Young

What is MODY?

Resembles Type 2 DM but occurs in the YOUTH

What usually causes MODY?

Loss of function mutations in Glucokinase that is responsible for creating ATP from glucose in beta cells

3 signs of MODY?

- Increased blood insulin - NO autoantibodies - NO ketones

3 signs of MODY?

- Increased blood insulin - NO autoantibodies - NO ketones

What is mom at risk for with Gestational DM?

C-section

What are 3 things that a baby is at risk for with Gestational DM?

- Neonatal Hypoglycemia - Congenital malformations - Macrosomia

If a neonate has hypoglycemia, what did the mother likely have and what is the baby at risk for?

- Mother had Gestational DM | - -> SEIZURE

If you see amyloid deposition in the islets, what type of DM should you think it is?

Type 2