Insulin 1 - Diabetes overview Flashcards

1
Q

How much glucose does the body require per day?

A

Minimum of 190 mg of glucose/day

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2
Q

What is the end result of uncontrolled diabetes mellitus?

A

Cardiovascular disease (macrovascular effects)
Neuropathy, nephropathy, retinopathy
Hyperlipidemias
Peripheral vascular disease

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3
Q

Signs/symptoms of DM?

A
Polyuria, polydipsia
Weight loss
Random plasma glucose over 200
Fasting glucose over 126
Glucose tolerance test over 200 mg/dL 2 hours after ingestion
A1c over 6.5%
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4
Q

What is Type 1 DM? Why is type 1 DM considered autoimmune in some cases?

A

Loss of B cells
Requires exogenous insulin for survival

It’s an autoimmune disease (type 1A is 90%)
80% of patients have antibodies to islet cell antigens at time of diagnosis, antibodies are directed to both cytoplasmic and membrane bound antigens as well as insulin

There is also non-immune or idiopathic type 1 (type 1B 10%)

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5
Q

What is Type 2 DM?

A

Insulin resistance, decreased release of insulin

20-30% of patients require insulin in addition to PO meds

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6
Q

What is Type 3 DM?

A

DM caused by secondary factors
Specific genetic defects in B cell function or insulin actions
Decreased insulin in the CNS could be linked to Alzheimers?

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7
Q

What is Type 4 DM?

A

Gestational DM
Occurs in 4% of pregnancies
Increases risk of T2DM in the mother after birth as well

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8
Q

What is the major morbidity associated with Type 1 DM?

A

Renal failure

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9
Q

What is the major morbidity associated with Type 2 DM?

A

Macrovascular disease

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10
Q

Risk factors for Type 1 diabetes?

A

Genetic (HLA Class II genes DR and DQ - 40 to 50% of risk)
Viruses (Enterovirus - coxsacki B related to polio and rhinovirus)
Family history (40-60% concordance in twins, although 75% do not have a family member with T1DM)

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11
Q

Risk factors for Type 2 diabetes?

A

Family history - genetics (4 fold increase in risk if have a family member with DM)
Ethnicity (African American, Latino, Native American, Asian American, Pacific Islander)
Obesity ~80% of affected individuals
Life style (Metabolic syndrome)

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12
Q

What is the function of A (alpha) cells in the pancreas?

A

Makes up 20% of cells in pancreas

Function is to mobilize fuel via gluconeogensis and glycogenolysis in the liver

Secretory products are proglucagon and glucagon, which increase the breakdown of glycogen/release of glucose to increase glucose levels in the bloodstream

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13
Q

What is the function of B (beta) cells in the pancreas?

A

Makes up 75% of cells in the pancreas

Promotes fuel storage and promotes growth

Secretes proinsulin, insulin, C-peptide, and amylin (to increase glucose storage)

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14
Q

What is the function of D (delta) cells in the pancreas?

A

Makes up 3-5% of cells in the pancreas

Inhibits secretory cells

Secretes somatostatin (inhibits insulin and glucagon excretion)

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15
Q

What is the function of F (PP) cells in the pancreas?

A

Makes up less than 2% of cells in the pancreas

Facilitates the digestive processes

Secretes pancreatic polypeptide

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16
Q

What occurs in the islets of langerhans in T2DM?

A

Alpha cell dysfunction results in secretion of inappropriately high levels of glucagon
Fewer beta cells, so you have insufficient secretion of insulin

17
Q

How much pancreatic function is lost at time of diagnosis?

A

50% of normal

18
Q

How is insulin made? How is it stored?

A

Proinsulin is converted to insulin and C-peptide in the golgi apparatus

It’s 51 amino acids in 2 peptide chains (A and B) linked by disulfide bridges

Stored in Beta cells as 2 atoms of zinc and 6 molecules of insulin

19
Q

What is C-peptide?

A

Insulin and C-peptide are released in equal amounts in response to elevated glucose
C-peptide has no known function but can be used as an index of insulin secretion

20
Q

How is insulin removed from the body?

A

It is degraded via hydrolysis of disulfide bonds then proteolysis (by insulinase)

Liver clears ~60% and kidneys clear the other 40%

Half life is 3-9 minutes

21
Q

Describe the mechanism of insulin release?

A

Pancreas is exposed to increased glucose, binds to GLUT-2 transporters on beta cells. Glucose is internalized and oxidized to ATP via the TCA cycle.

Increased ATP levels causes ATP-dependent K+ channels to close, which depolarizes the cell, opening voltage gated Calcium channels.

Calcium rushing in stimulates the exocytosis of insulin granules into the blood

22
Q

How do sulfonylureas work in the release of insulin?

A

They block ATP dependent K+ channels, thus depolarizing the cell and opening Ca++ channels to stimulate insulin release

23
Q

Describe the mechanism of insulin action

A

Insulin stimulates glucose uptake into target tissues by activating GLUT4 receptors

Insulin initiates phosphorylation cascade within the cells, translocates glucose transporters from inside cell to the cell surface

Glucose enters via facilitated diffusion through transporters

The glucose is then used for energy or stored

24
Q

Where are GLUT1 transporters found? What is their function?

A

GLUT1 transporters are found in all tissues, red blood cells and brain

Function - basal uptake of glucose, transport across the BBB

25
Q

Where are GLUT2 transporters found? What is their function?

A

Found in beta cells of the pancreas, liver, and kidney

Function - regulation of insulin release

26
Q

Where are GLUT3 transporters found? What is their function?

A

Brain, kidney, placenta

Function - uptake into neurons

27
Q

Where are GLUT4 transporters found? What is their function?

A

Muscle, adipose

Function - insulin mediated glucose uptake

28
Q

Where are GLUT5 transporters found? What is their function?

A

Gut, kidney

Absorption of fructose

29
Q

What effect does insulin have in the liver?

A

Stimulates the storage of glucose as glycogen, conversion to fatty acids/VLDL then adipose

Inhibits glycogenolysis (breakdown of glycogen), gluconeogenesis (synthesis of glucose), conversion of fatty acid to ketones

30
Q

What effect does insulin have in skeletal muscle?

A

Stimulates the storage of glucose as glycogen, storage of amino acids as proteins

Inhibits protein degradation to amino acids

31
Q

What effect does insulin have in adipose tissue?

A

Stimulates storage of fatty acids as triglycerides

Inhibits the conversion of TG’s to fatty acids